Showing papers by "Xiaoyuan Chen published in 2019"
TL;DR: It is believed that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve the ability to combat cancers.
Abstract: The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.
1,721 citations
TL;DR: The fabrication of copper peroxide (CP) nanodot is reported, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2.
Abstract: Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.
634 citations
TL;DR: This review focuses on summarizing organic dyes emitting at a biological transparency window termed the near‐infrared‐II (NIR‐II) window, where minimal light interaction with the surrounding tissues allows photons to travel nearly unperturbed throughout the body.
Abstract: Fluorescence bioimaging affords a vital tool for both researchers and surgeons to molecularly target a variety of biological tissues and processes. This review focuses on summarizing organic dyes emitting at a biological transparency window termed the near-infrared-II (NIR-II) window, where minimal light interaction with the surrounding tissues allows photons to travel nearly unperturbed throughout the body. NIR-II fluorescence imaging overcomes the penetration/contrast bottleneck of imaging in the visible region, making it a remarkable modality for early diagnosis of cancer and highly sensitive tumor surgery. Due to their convenient bioconjugation with peptides/antibodies, NIR-II molecular dyes are desirable candidates for targeted cancer imaging, significantly overcoming the autofluorescence/scattering issues for deep tissue molecular imaging. To promote the clinical translation of NIR-II bioimaging, advancements in the high-performance small molecule-derived probes are critically important. Here, molecules with clinical potential for NIR-II imaging are discussed, summarizing the synthesis and chemical structures of NIR-II dyes, chemical and optical properties of NIR-II dyes, bioconjugation and biological behavior of NIR-II dyes, whole body imaging with NIR-II dyes for cancer detection and surgery, as well as NIR-II fluorescence microscopy imaging. A key perspective on the direction of NIR-II molecular dyes for cancer imaging and surgery is also discussed.
530 citations
TL;DR: A comprehensive review on the latest remarkable advances in BBB-crossing nanotechnology, with an emphasis on the judicious design of multifunctional nanoplatforms for effective BBB penetration, efficient tumour accumulation, precise tumour imaging, and significant tumour inhibition of brain cancer.
Abstract: Brain cancer, especially the most common type of glioblastoma, is highly invasive and known as one of the most devastating and deadly neoplasms. Despite surgical and medical advances, the prognosis for most brain cancer patients remains dismal and the median survival rarely exceeds 16 months. Drug delivery to the brain is significantly hindered by the existence of the blood–brain barrier (BBB), which serves as a protective semi-permeable membrane for the central nervous system. Recent breakthroughs in nanotechnology have yielded multifunctional theranostic nanoplatforms with the ability to cross or bypass the BBB, enabling accurate diagnosis and effective treatment of brain tumours. Herein, we make our efforts to present a comprehensive review on the latest remarkable advances in BBB-crossing nanotechnology, with an emphasis on the judicious design of multifunctional nanoplatforms for effective BBB penetration, efficient tumour accumulation, precise tumour imaging, and significant tumour inhibition of brain cancer. The detailed elucidation of BBB-crossing nanotechnology in this review is anticipated to attract broad interest from researchers in diverse fields to participate in the establishment of powerful BBB-crossing nanoplatforms for highly efficient brain cancer theranostics.
322 citations
TL;DR: This review introduces the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties, and outlines the design considerations for nanocarbon materials as the key unifying themes.
Abstract: Nanocarbons with different dimensions (e.g., 0D fullerenes and carbon nanodots, 1D carbon nanotubes and graphene nanoribbons, 2D graphene and graphene oxides, and 3D nanodiamonds) have attracted enormous interest for applications ranging from electronics, optoelectronics, and photovoltaics to sensing, bioimaging, and therapeutics due to their unique physical and chemical properties. Among them, nanocarbon-based theranostics (i.e., therapeutics and diagnostics) is one of the most intensively studied applications, as these nanocarbon materials serve as excellent biosensors, versatile drug/gene carriers for specific targeting in vivo, effective photothermal nanoagents for cancer therapy, and promising fluorescent nanolabels for cell and tissue imaging. This review provides a systematic overview of the latest theranostic applications of nanocarbon materials with a comprehensive comparison of the characteristics of different nanocarbon materials and their influences on theranostic applications. We first introduce the different carbon allotropes that can be used for theranostic applications with their respective preparation and surface functionalization approaches as well as their physical and chemical properties. Theranostic applications are described separately for both in vitro and in vivo systems by highlighting the protocols and the studied biosystems, followed by the toxicity and biodegradability implications. Finally, this review outlines the design considerations for nanocarbon materials as the key unifying themes that will serve as a foundational first principle for researchers to study, investigate, and generate effective, biocompatible, and nontoxic nanocarbon materials-based models for cancer theranostics applications. Finally, we summarize the review with an outlook on the challenges and novel theranostic protocols using nanocarbon materials for hard-to-treat cancers and other diseases. This review intends to present a comprehensive guideline for researchers in nanotechnology and biomedicine on the selection strategy of nanocarbon materials according to their specific requirements.
318 citations
TL;DR: This review is based on the principles of cancer immunotherapy and the combined treatment design reflected by advances in materials science, including the structures of nanoplatforms and their underlying mechanisms towards cancer.
Abstract: In recent years, conventional treatments including surgery, chemotherapy and radiotherapy have been the main approaches in tumour therapy. Cancer immunotherapy is a new therapeutic modality to fight cancer by harnessing the power of patients’ own immune system. Ongoing research related to these therapies has demonstrated their advantages and intrinsic limitations. Nanomaterial-based platforms are utilized in these emerging fields. In particular, a combination of other treatment methods with cancer immunotherapy to achieve precision medicine and prevent recurrence and metastasis, could improve patients’ outcome. The combined multiple treatments have superior efficacy to any monotherapy alone in producing improved anti-cancer activity. Therefore, it's necessary to summarise research advances in nanomaterial-based combination cancer immunotherapy contributing to clinical transformation. This review is based on the principles of cancer immunotherapy and the combined treatment design reflected by advances in materials science, including the structures of nanoplatforms and their underlying mechanisms towards cancer. The ultimate goals are to stimulate the design of better strategies for versatile use in the future based on biomaterial engineering methods to enhance the efficacy of combined cancer treatments, and to provide new ideas for the prospects of a synergistic cancer combination immunotherapy for clinical application transformation.
251 citations
TL;DR: Recent progress in probing MRI relaxivity of MNPs based on structural features at the molecular and atomic scales is reviewed and a special emphasis is placed on bridging the gaps between classical simplistic models and modern MNPs with elegant structural complexity.
Abstract: Magnetic nanoparticles (MNPs) have been extensively explored as magnetic resonance imaging (MRI) contrast agents. With the increasing complexity in the structure of modern MNPs, the classical Solomon-Bloembergen-Morgan and the outer-sphere quantum mechanical theories established on simplistic models have encountered limitations for defining the emergent phenomena of relaxation enhancement in MRI. Recent progress in probing MRI relaxivity of MNPs based on structural features at the molecular and atomic scales is reviewed, namely, the structure-relaxivity relationships, including size, shape, crystal structure, surface modification, and assembled structure. A special emphasis is placed on bridging the gaps between classical simplistic models and modern MNPs with elegant structural complexity. In the pursuit of novel MRI contrast agents, it is hoped that this review will spur the critical thinking for design and engineering of novel MNPs for MRI applications across a broad spectrum of research fields.
249 citations
TL;DR: This review summarizes the current understanding of the physiological structure of BBB, and provides various nanomaterial-based BBB-crossing strategies for brain delivery of theranostic agents.
235 citations
TL;DR: The potent antitumor effect of the LaCIONPs is demonstrated by both in vitro and in vivo results, and is a promising nanomedicine for tumor‐specific chemo/chemodynamic combination therapy.
Abstract: The combination of chemotherapeutic drugs and reactive oxygen species (ROS) is a promising strategy to achieve improved anticancer effect. Herein, a nanomedicine (LaCIONPs) that can achieve tumor-specific chemotherapeutic drug release and ROS generation is developed for cancer chemo/chemodynamic combination therapy. The LaCIONPs are constructed by encapsulation of iron oxide nanoparticles (IONPs) and β-lapachone (La) in nanostructure assembled by hydrogen peroxide (H2O2)-responsive polyprodrug and pH-responsive polymer. Through the enhanced permeability and retention effect, the nanosized LaCIONPs can accumulate in tumor tissue. After the LaCIONPs are internalized by tumor cells, the structure of LaCIONPs is disintegrated in acidic intracellular environment, leading to rapid release of La and iron ions. Then the released La generates massive H2O2 through tumor specific catalysis. On the one hand, H2O2 further reacts with iron ions to produce highly toxic hydroxyl radicals for chemodynamic therapy. On the other hand, H2O2 also activates the release of camptothecin from the polyprodrug for chemotherapy. The potent antitumor effect of the LaCIONPs is demonstrated by both in vitro and in vivo results. Therefore, the LaCIONP is a promising nanomedicine for tumor-specific chemo/chemodynamic combination therapy.
205 citations
TL;DR: This review systematically describes the interaction mechanisms between X-rays and nanosystems, and provides an overview of X-ray-sensitive materials and the recent progress on X- Ray-activated nanosSystems for cancer-associated theranostic applications.
Abstract: X-rays are widely applied in clinical medical facilities for radiotherapy (RT) and biomedical imaging. However, the sole use of X-rays for cancer treatment leads to insufficient radiation energy deposition due to the low X-ray attenuation coefficients of living tissues and organs, producing unavoidable excessive radiation doses with serious side effects to healthy body parts. Over the past decade, developments in materials science and nanotechnology have led to rapid progress in the field of X-ray-activated tumor-targeting nanosystems, which are able to tackle even systemic tumors and relieve the burden of exposure to large radiation doses. Additionally, novel imaging contrast agents and techniques have also been developed. In comparison with conventional external light sources (e.g., near infrared), the X-ray technique is ideal for the activation of nanosystems for cancer treatment and biomedical imaging applications due to its nearly unlimited penetration depth in living tissues and organisms. In this review, we systematically describe the interaction mechanisms between X-rays and nanosystems, and provide an overview of X-ray-sensitive materials and the recent progress on X-ray-activated nanosystems for cancer-associated theranostic applications.
190 citations
TL;DR: In vivo results indicate that the cascade of ROS generation and anti-tumor drug release can effectively inhibit tumor growth, and this design of nanomedicine with cascade reactions offers a promising strategy to enhance anti-Tumor efficacy.
Abstract: Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy through the combination of CDT and chemotherapy. Here we report a pH/ROS dual-responsive nanomedicine consisting of β-lapachone (Lap), a pH-responsive polymer, and a ROS-responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH-triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS-induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor-drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.
TL;DR: In vivo results indicate that the all-in-one polymersomal nanoformulation (CCPS/HPPH/DOX) increases mature DCs in tumor-draining lymph nodes and CD8+ T cells in tumor tissues to inhibit primary and distant MC38 tumor growth following a single intravenous injection with a low dose of DOX and HPPH.
Abstract: A cancer vaccine is an important form of immunotherapy. Given their effectiveness for antigen processing and presentation, dendritic cells (DCs) have been exploited in the development of a therapeutic vaccine. Herein, a versatile polymersomal nanoformulation that enables generation of tumor-associated antigens (TAAs) and simultaneously serves as adjuvant for an in situ DC vaccine is reported. The chimeric cross-linked polymersome (CCPS) is acquired from self-assembly of a triblock copolymer, polyethylene glycol-poly(methyl methyacrylate- co-2-amino ethyl methacrylate (thiol/amine))-poly 2-(dimethylamino)ethyl methacrylate (PEG-P(MMA- co-AEMA (SH/NH2)-PDMA). CCPS can encapsulate low-dose doxorubicin hydrochloride (DOX) to induce immunogenic cell death (ICD) and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), a photosensitizer to facilitate photodynamic therapy (PDT) for reactive oxygen species (ROS) generation. This combination is able to enhance the population of TAAs and DC recruitment, eliciting an immune response cascade. In addition, CCPS with primary and tertiary amines act as adjuvant, both of which can stimulate DCs recruited to form an in situ DC vaccine after combination with TAAs for MC38 colorectal cancer treatment. In vivo results indicate that the all-in-one polymersomal nanoformulation (CCPS/HPPH/DOX) increases mature DCs in tumor-draining lymph nodes (tdLNs) and CD8+ T cells in tumor tissues to inhibit primary and distant MC38 tumor growth following a single intravenous injection with a low dose of DOX and HPPH.
TL;DR: In’situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2 -evolving chemoradiotherapy is proposed.
Abstract: Tumor hypoxia, the "Achilles' heel" of current cancer therapies, is indispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2 -evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers, whereas the MOF scaffold acts as a container to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase-like nanohybrid significantly enhances the radiotherapy effect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy. This hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theranostic nanomedicines.
TL;DR: A sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT) against MDR bacteria is reported, indicating that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis.
Abstract: Rapid emergence of multidrug resistant (MDR) “superbugs” poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting...
TL;DR: This study engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a Nir-II quantum yield of 21.2% with prolonged circulation time and afforded high-resolution microvessel imaging.
Abstract: NIR-II fluorescence imaging greatly reduces scattering coefficients for nearly all tissue types at long wavelengths, benefiting deep tissue imaging. However, most of the NIR-II fluorophores suffer from low quantum yields and/or short circulation time that limit the quality of NIR-II imaging. Here, we engineered a supramolecular assembly of protein complex with lodged cyanine dyes to produce a brilliant NIR-II fluorophore, providing a NIR-II quantum yield of 21.2% with prolonged circulation time. Computational modeling revealed the mechanism for fluorescence enhancement and identified key parameters governing albumin complex for NIR-II fluorophores. Our complex afforded high-resolution microvessel imaging, with a 3-hour imaging window compared to 2 min for free dye alone. Furthermore, the complexation strategy was applied to an antibody-derived assembly, offering high-contrast tumor imaging without affecting the targeting ability of the antibody. This study provides a facile strategy for producing high-performance NIR-II fluorophores by chaperoning cyanine dyes with functional proteins.
TL;DR: The first combination of antibacterial sonodynamic therapy and antivirulence immunotherapy, which promises a new way for antibiotic‐free nanotheranostics to robustly combat MDR bacterial infections, is presented.
Abstract: Antibiotic-free methods hold particular promise for preventing and controlling multidrug-resistant (MDR) bacterial infection via eradiation of bacteria and their pathogenic virulence. A facile and bioinspired strategy is presented for bridging antibacterial sonodynamic therapy and antivirulence immunotherapy. As a proof-of-concept, an antibody which neutralizes alpha-toxin of methicillin-resistant Staphylococcus aureus (MRSA) is genetically engineered on to the surface of cell membrane nanovesicles, which then undergo sonosensitizer encapsulation. Compared with conventional passive virulence absorption using natural red blood membrane, the highly active antibody-toxin interaction enables the nanovesicles to capture virulence more potently in vitro. Upon ultrasound activation, the sonosensitizers efficiently generate reactive oxygen species to kill bacteria and accelerate the virulence clearance. In vivo optical imaging shows that the antibody-piloted nanocapturer can successfully locate MRSA infection and accurately distinguish the foci from sterile inflammation. In situ magnetic resonance imaging and oxyhemoglobin saturation detection visualize the treatment progression, revealing a complete sono-immunotherapeutic eradication of MRSA myositis in mice. The first combination of antibacterial sonodynamic therapy and antivirulence immunotherapy, which promises a new way for antibiotic-free nanotheranostics to robustly combat MDR bacterial infections, is presented.
TL;DR: This review contributes towards a systematic understanding of the mechanism of shape-dependent effects on nanoparticles (NPs) for elaborating and predicting their properties and applications based on the past two decades of research.
Abstract: This review contributes towards a systematic understanding of the mechanism of shape-dependent effects on nanoparticles (NPs) for elaborating and predicting their properties and applications based on the past two decades of research. Recently, the significance of shape-dependent physical chemistry and biomedicine has drawn ever increasing attention. While there has been a great deal of effort to utilize NPs with different morphologies in these fields, so far research studies are largely localized in particular materials, synthetic methods, or biomedical applications, and have ignored the interactional and interdependent relationships of these areas. This review is a comprehensive description of the NP shapes from theory, synthesis, property to application. We figure out the roles that shape plays in the properties of different kinds of nanomaterials together with physicochemical and biomedical applications. Through systematic elaboration of these shape-dependent impacts, better utilization of nanomaterials with diverse morphologies would be realized and definite strategies would be expected for breakthroughs in these fields. In addition, we have proposed some critical challenges and open problems that need to be addressed in nanotechnology.
TL;DR: A novel one‐step wet‐chemical method is first proposed for protein‐directed synthesis of 2D MnO2 nanosheets (M‐NSs), in which the size and thickness can be easily adjusted by the protein dosage, and the resulting M‐NS exhibits excellent enzyme‐like activity to catalyze the oxidation of glucose.
Abstract: 2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug-loading capacity, and excellent photothermal conversion. However, few studies report their "enzyme-like" catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one-step wet-chemical method is first proposed for protein-directed synthesis of 2D MnO2 nanosheets (M-NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono-chemical approach is introduced for surface functionalization of the M-NSs with high dispersity/stability as well as metal-cation-chelating capacity, which can not only chelate 64 Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn2+ for enhanced biosafety. Interestingly, the resulting M-NS exhibits excellent enzyme-like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well-designed M-NS can achieve effective photoacoustic-imaging-guided synergistic starvation-enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small-sized and ultrathin M-NSs, which will broaden the application of 2D nanomaterials.
TL;DR: This Account summarizes the recent work on the development of small molecular semiconducting perylene diimide (SPDI) for advanced phototheranostics and considers the design of SPDIPTs, which have diverse biomedical applications and offer many opportunities for advancing nanomedicine.
Abstract: Precision medicine requires noninvasive and accurate early diagnosis and individually appropriate treatments. Phototheranostics has been considered a frontier precision medical technology to provide rapid and safe disease localization and efficient cure. Harnessing the power of advanced nanomedicine with photonics, phototheranostics is rapidly developing and progressively becoming irreplaceable in modern medicine. Nanoscale semiconducting materials, such as inorganic semiconductors, organic conjugated polymers, and small molecules with photonic properties, have been extensively explored in medical imaging (fluorescence imaging, optical coherence tomography, and photoacoustic [PA] imaging) and phototherapy (photothermal, photodynamic, and photocontrolled combination therapies). In practical clinical applications, organic semiconducting materials, because of their biocompatibility and natural metabolism, are preferred over inorganic materials for phototheranostics. Supramolecular self-assembly is considered a significant method for preparing organic detachable and multifunctional phototheranostics, as supramolecular interactions, such as π-π interactions, hydrogen bonding, hydrophobic effects, and electrostatic interactions, are non-covalent and dynamic. Developing new and effective organic supramolecular phototheranostics requires exploration of well-designed basic building blocks with optical properties, understanding of the assembly at the nanoscale, and optimization of the phototheranostics with unique and distinctive multifunctional efficacy. In this Account, we summarize our recent work on the development of small molecular semiconducting perylene diimide (SPDI) for advanced phototheranostics. SPDI is modified to have strong near-infrared absorption beyond 700 nm by the push-pull electronic effect and owns the merits of remarkable photostability, large extinction coefficient, and high photothermal conversion efficiency. By hydrophilic modification, the amphiphile can self-assemble into a nanomicellar structure that allows PA imaging and can serve as a photothermal conversion agent. After theranostics delivery is achieved, this SPDI can be further functionalized for multimodality imaging and photothermally triggered multimodal synergistic therapy. Several well-designed asymmetric structures of SPDI can be obtained by stepwise modification of imides. It is noteworthy that the self-assembly of SPDI is controllable, allowing the preparation of different-sized spherical nanoparticles and rodlike nanoparticles and nanodroplets. For biomedical applications of SPDI phototheranostics (SPDIPTs), the size effect of SPDIPTs has been highlighted in lymph node mapping and cancer imaging. The PA properties and targeting peptide modification of SPDIPTs have brought about the ultrasensitive imaging of early thrombus. The supramolecular nanoconstructs of SPDIPTs further permit multimodality-imaging-guided cancer therapy. In brief, the design of SPDIPTs considers synthetic chemistry, supramolecular self-assembly, nanotechnology, and photonics. Furthermore, SPDIPTs have diverse biomedical applications and offer many opportunities for advancing nanomedicine.
TL;DR: The development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (Fe3O4-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy leads to greatly improved therapeutic efficacy than monotherapies.
Abstract: In the present study, we report the development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (Fe3O4-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy. The amphiphilic Fe3O4-Au JNPs were grafted with poly(ethylene glycol) (PEG) on the Au surface and ROS-generating poly(lipid hydroperoxide) (PLHP) on the Fe3O4 surface, respectively, which were then assembled into vesicles containing two closely attached Fe3O4-Au NPs layers in opposite directions. The self-assembly mechanism of the bilayered vesicles was elucidated by performing a series of numerical simulations. The enhanced optical properties of the bilayered vesicles were verified by the calculated results and experimental data. The vesicles exhibited enhanced T2 relaxivity and photoacoustic properties over single JNPs due to the interparticle magnetic dipole interaction and plasmonic coupling. In particular, the vesicles are pH responsive and disassemble into single JNPs in the acidic tumor environment, activating an intracellular biochemical reaction between the grafted PLHP and released ferrous ions (Fe2+) from Fe3O4 NPs, resulting in highly efficient local ROS generation and increased intracellular oxidative stress. In combination with the release of doxorubicin (DOX), the vesicles combine ROS-mediated cytotoxicity and DOX-induced chemotherapy, leading to greatly improved therapeutic efficacy than monotherapies. High tumor accumulation efficiency and fast vesicle clearance from the body were also confirmed by positron emission tomography (PET) imaging of radioisotope 64Cu-labeled vesicles.
TL;DR: Advanced nan technology in the construction of nanomaterials (NMs) for precision imaging‐guided surgery (IGS) as well as surgery‐assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS‐assisted precision synergistic cancer therapy.
Abstract: Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging-guided surgery (IGS) as well as surgery-assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS-assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS-assisted precision synergistic cancer therapy.
TL;DR: As indicated by in vivo tumor formation experiments, tumorigenicity was signi?cantly suppressed after one radiotherapy treatment with the Au8NCs, and tumors treated with the nanosensitizer exhibited an inhibition rate of 74.2%.
Abstract: Gold nanoclusters have become promising radiosensitizers due to their ultrasmall size and robust ability to adsorb, scatter, and re-emit radiation. However, most of the previously reported gold nanocluster radiosensitizers do not have a precise atomic structure, causing difficulties in understanding the structure-activity relationship. In this study, a structurally defined gold-levonorgestrel nanocluster consisting of Au8(C21H27O2)8 (Au8NC) with bright luminescence (58.7% quantum yield) and satisfactory biocompatibility was demonstrated as a nanoradiosensitizer. When the Au8NCs were irradiated with X-rays, they produced reactive oxygen species (ROS), resulting in irreversible cell apoptosis. As indicated by in vivo tumor formation experiments, tumorigenicity was significantly suppressed after one radiotherapy treatment with the Au8NCs. In addition, compared with tumors treated with X-rays (4 Gy) alone, tumors treated with the nanosensitizer exhibited an inhibition rate of 74.2%. This study contributes to the development of atomically precise gold nanoclusters as efficient radiosensitizers.
TL;DR: This review summarizes the progress of supramolecular theranostics on the basis of host-guest chemistry benefiting from their fantastic topological structures and outstanding supramolescular chemistry to provide new methodologies to overcome the obstacles faced by the traditional theranostic systems.
Abstract: Macrocyclic hosts, such as cyclodextrins, calixarenes, cucurbiturils, and pillararenes, exhibit unparalleled advantages in disease diagnosis and therapy over the past years by fully taking advantage of their host-guest molecular recognitions. The dynamic nature of the non-covalent interactions and selective host-guest complexation endow the resultant nanomaterials with intriguing properties, holding promising potentials in theranostic fields. Interestingly, the differences in microenvironment between the abnormal and normal cells/tissues can be employed as the stimuli to modulate the host-guest interactions, realizing the purpose of precise diagnosis and specific delivery of drugs to lesion sites. In this review, we summarize the progress of supramolecular theranostics on the basis of host-guest chemistry benefiting from their fantastic topological structures and outstanding supramolecular chemistry. These state-of-the-art examples provide new methodologies to overcome the obstacles faced by the traditional theranostic systems, promoting their clinical translations.
TL;DR: A super-contrast NIR-II fluorophore IR-BEMC6P with enhanced quantum yield is developed and the excretion mechanism is identified.
Abstract: In vivo molecular imaging in the “transparent” near-infrared II (NIR-II) window has demonstrated impressive benefits in reaching millimeter penetration depths with high specificity and imaging quality. Previous NIR-II molecular imaging generally relied on high hepatic uptake fluorophores with an unclear mechanism and antibody-derived conjugates, suffering from inevitable nonspecific retention in the main organs/skin with a relatively low signal-to-background ratio. It is still challenging to synthesize a NIR-II fluorophore with both high quantum yield and minimal liver-retention feature. Herein, we identified the structural design and excretion mechanism of novel NIR-II fluorophores for NIR-II molecular imaging with an extremely clean background. With the optimized renally excreted fluorophore–peptide conjugates, superior NIR-II targeting imaging was accompanied by the improved signal-to-background ratio during tumor detection with reducing off-target tissue exposure. An unprecedented NIR-II imaging-guided microsurgery was achieved using such an imaging platform, which provides us with a great preclinical example to accelerate the potential clinical translation of NIR-II imaging.
TL;DR: A comprehensive overview of the recent advances in nanotechnology-enhanced X-ray-excited deep theranostic imaging and therapeutic methodologies is presented, with an emphasis on the design of multifunctional nanomaterials for contrast-enhancing computed tomography (CT) imaging, X- Ray- Excited optical luminescence (XEOL) Imaging, and X-Ray-excite multimodal synchronous/synergistic therapy.
Abstract: The advancements in nanotechnology have created multifunctional nanomaterials aimed at enhancing diagnostic accuracy and treatment efficacy for cancer. However, the ability to target deep-seated tumors remains one of the most critical challenges for certain nanomedicine applications. To this end, X-ray-excited theranostic techniques provide a means of overcoming the limits of light penetration and tissue attenuation. Herein, a comprehensive overview of the recent advances in nanotechnology-enhanced X-ray-excited imaging and therapeutic methodologies is presented, with an emphasis on the design of multifunctional nanomaterials for contrast-enhanced computed tomography (CT) imaging, X-ray-excited optical luminescence (XEOL) imaging, and X-ray-excited multimodal synchronous/synergistic therapy. The latter is based on the concurrent use of radiotherapy with chemotherapy, gas therapy, photodynamic therapy, or immunotherapy. Moreover, the featured biomedical applications of X-ray-excited deep theranostics are discussed to highlight the advantages of X-ray in high-sensitivity detection and efficient elimination of malignant tumors. Finally, key issues and technical challenges associated with this deep theranostic technology are identified, with the intention of advancing its translation into the clinic.
TL;DR: It is demonstrated that autologous separation and administration of cellular membranes and anticancer cisplatin (Pt)‐loaded PDTC@GNPs lead to almost complete tumor ablation in a subcutaneous model and effectively inhibit tumor recurrence in a postsurgery model.
TL;DR: The findings reveal that OA@BCMNs may provide a clinical basis for improving oncolytic virotherapy by overcoming undesired antiviral immunity and enhancing cancer cell selectivity via biomimetic synthesis approaches.
Abstract: Currently, various oncolytic adenoviruses (OA) are being explored in both preclinical and clinical virotherapy. However, the pre-existing neutralizing antibodies (nAbs) and poor targeting delivery are major obstacles for systemically administered OA. Therefore, we designed bioengineered cell membrane nanovesicles (BCMNs) that harbor targeting ligands to achieve robust antiviral immune shielding and targeting capabilities for oncolytic virotherapy. We employed two distinct biomimetic synthetic approaches: the first is based on in vitro genetic membrane engineering to embed targeting ligands on the cell membrane, and the second is based on in vivo expression of CRISPR-engineered targeting ligands on red-blood-cell membranes. The results indicate that both bioengineering approaches preserve the infectivity and replication capacity of OA in the presence of nAbs, in vitro and in vivo. Notably, OA@BCMNs demonstrated a significant suppression of the induced innate and adaptive immune responses against OA. Enhanced targeting delivery, viral oncolysis, and survival benefits in multiple xenograft models were observed without overt toxicity. These findings reveal that OA@BCMNs may provide a clinical basis for improving oncolytic virotherapy by overcoming undesired antiviral immunity and enhancing cancer cell selectivity via biomimetic synthesis approaches.
TL;DR: This sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer‐targeted delivery capability and enhanced reactive oxygen species production via triple‐regulated approaches, including down‐regulation of SOD2, depletion of glutathione, and generation of Fenton reaction.
TL;DR: An ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized hollow mesoporous organosilica nanoparticles with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties designed for oxygen-independent X-ray-activated synergistic therapy.
Abstract: The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate •OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of •OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers. A common failure of many cancer treatments is attributed to the resistance imparted by tumour hypoxia. Here, the authors report on the generic synthesis of small-sized hollow mesoporous organosilica nanoparticles which are designed for oxygen-independent X-ray-activated synergistic therapy.
TL;DR: The enhanced theranostic capability of zinc(II)-dipicolylamine-assisted assembly of ICG, as well as simultaneous targeted gene delivery in an experimental mouse model of cancer are shown.
Abstract: We report the rational design of coordination-driven self-assembly metal-organic nanostructures for multifunctional nanotheranostics. Zinc(II) coordination-based nano-formulations capable of loading indocyanine green (ICG) and therapeutic genes were prepared to achieve a fluorescence/photoacoustic imaging-guided combination photo/gene therapy strategy. We showed the enhanced theranostic capability of zinc(II)-dipicolylamine-assisted assembly of ICG, as well as simultaneous targeted gene delivery in an experimental mouse model of cancer. Such a co-assembly strategy provides a facile way to achieve combined therapeutic functions for personalized nanomedicine.