Showing papers by "Xiaoyuan Chen published in 2017"

Nanotechnology for Multimodal Synergistic Cancer Therapy

Abstract: The complexity, diversity, and heterogeneity of tumors seriously undermine the therapeutic potential of treatment. Therefore, the current trend in clinical research has gradually shifted from a focus on monotherapy to combination therapy for enhanced treatment efficacy. More importantly, the cooperative enhancement interactions between several types of monotherapy contribute to the naissance of multimodal synergistic therapy, which results in remarkable superadditive (namely “1 + 1 > 2”) effects, stronger than any single therapy or their theoretical combination. In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergistic therapy as well as the intensive exploration of the underlying synergistic mechanisms for explaining the significant improvements in synergistic therapeutic outcome. Furtherm...

Diverse Applications of Nanomedicine

Abstract: The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.

Rethinking cancer nanotheranostics.

Abstract: Advances in nanoparticle synthesis and engineering have produced nanoscale agents affording both therapeutic and diagnostic functions that are often referred to by the portmanteau 'nanotheranostics'. The field is associated with many applications in the clinic, especially in cancer management. These include patient stratification, drug-release monitoring, imaging-guided focal therapy and post-treatment response monitoring. Recent advances in nanotheranostics have expanded this notion and enabled the characterization of individual tumours, the prediction of nanoparticle-tumour interactions, and the creation of tailor-designed nanomedicines for individualized treatment. Some of these applications require breaking the dogma that a nanotheranostic must combine both therapeutic and diagnostic agents within a single, physical entity; instead, it can be a general approach in which diagnosis and therapy are interwoven to solve clinical issues and improve treatment outcomes. In this Review, we describe the evolution and state of the art of cancer nanotheranostics, with an emphasis on clinical impact and translation.

Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment

Abstract: Nanovehicles can efficiently carry and deliver anticancer agents to tumour sites Compared with normal tissue, the tumour microenvironment has some unique properties, such as vascular abnormalities, hypoxia and acidic pH There are many types of cells, including tumour cells, macrophages, immune and fibroblast cells, fed by defective blood vessels in the solid tumour Exploiting the tumour microenvironment can benefit the design of nanoparticles for enhanced therapeutic effectiveness In this review article, we summarized the recent progress in various nanoformulations for cancer therapy, with a special emphasis on tumour microenvironment stimuli-responsive ones Numerous tumour microenvironment modulation strategies with promising cancer therapeutic efficacy have also been highlighted Future challenges and opportunities of design consideration are also discussed in detail We believe that these tumour microenvironment modulation strategies offer a good chance for the practical translation of nanoparticle formulas into clinic

Glucose-Responsive Sequential Generation of Hydrogen Peroxide and Nitric Oxide for Synergistic Cancer Starving-Like/Gas Therapy.

Abstract: Glucose is a key energy supplier and nutrient for tumor growth. Herein, inspired by the glucose oxidase (GOx)-assisted conversion of glucose into gluconic acid and toxic H2 O2 , a novel treatment paradigm of starving-like therapy is developed for significant tumor-killing effects, more effective than conventional starving therapy by only cutting off the energy supply. Furthermore, the generated acidic H2 O2 can oxidize l-Arginine (l-Arg) into NO for enhanced gas therapy. By using hollow mesoporous organosilica nanoparticle (HMON) as a biocompatible/biodegradable nanocarrier for the co-delivery of GOx and l-Arg, a novel glucose-responsive nanomedicine (l-Arg-HMON-GOx) has been for the first time constructed for synergistic cancer starving-like/gas therapy without the need of external excitation, which yields a remarkable H2 O2 -NO cooperative anticancer effect with minimal adverse effect.

Current detection technologies for circulating tumor cells

Abstract: Circulating tumor cells (CTCs) are cancer cells that circulate in the blood stream after being naturally shed from original or metastatic tumors, and can lead to a new fatal metastasis. CTCs have become a hotspot research field during the last decade. Detection of CTCs, as a liquid biopsy of tumors, can be used for early diagnosis of cancers, earlier evaluation of cancer recurrence and chemotherapeutic efficacy, and choice of individual sensitive anti-cancer drugs. Therefore, CTC detection is a crucial tool to fight against cancer. Herein, we classify the currently reported CTC detection technologies, introduce some representative samples for each technology, conclude the advantages and limitations, and give a future perspective including the challenges and opportunities of CTC detection.

Activatable Singlet Oxygen Generation from Lipid Hydroperoxide Nanoparticles for Cancer Therapy

Abstract: Reactive oxygen species (ROS)-induced apoptosis is a widely practiced strategy for cancer therapy. Although photodynamic therapy (PDT) takes advantage of the spatial–temporal control of ROS generation, the meticulous participation of light, photosensitizer, and oxygen greatly hinders the broad application of PDT as a first-line cancer treatment option. An activatable system has been developed that enables tumor-specific singlet oxygen (1O2) generation for cancer therapy, based on a Fenton-like reaction between linoleic acid hydroperoxide (LAHP) tethered on iron oxide nanoparticles (IO NPs) and the released iron(II) ions from IO NPs under acidic-pH condition. The IO-LAHP NPs are able to induce efficient apoptotic cancer cell death both in vitro and in vivo through tumor-specific 1O2 generation and subsequent ROS mediated mechanism. This study demonstrates the effectiveness of modulating biochemical reactions as a ROS source to exert cancer death.

Cancer-Associated, Stimuli-Driven, Turn on Theranostics for Multimodality Imaging and Therapy.

Abstract: Advances in bioinformatics, genomics, proteomics, and metabolomics have facilitated the development of novel anticancer agents that have decreased side effects and increased safety. Theranostics, systems that have combined therapeutic effects and diagnostic capabilities, have garnered increasing attention recently because of their potential use in personalized medicine, including cancer-targeting treatments for patients. One interesting approach to achieving this potential involves the development of cancer-associated, stimuli-driven, turn on theranostics. Multicomponent constructs of this type would have the capability of selectively delivering therapeutic reagents into cancer cells or tumor tissues while simultaneously generating unique signals that can be readily monitored under both in vitro and in vivo conditions. Specifically, their combined anticancer activities and selective visual signal respond to cancer-associated stimuli, would make these theranostic agents more highly efficient and specific for cancer treatment and diagnosis. This article focuses on the progress of stimuli-responsive turn on theranostics that activate diagnostic signals and release therapeutic reagents in response to the cancer-associated stimuli. The present article not only provides the fundamental backgrounds of diagnostic and therapeutic tools that have been widely utilized for developing theranostic agents, but also discusses the current approaches for developing stimuli-responsive turn on theranostics.

Engineering Phototheranostic Nanoscale Metal-Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy.

Abstract: Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal–organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (...

Ultrasmall Semimetal Nanoparticles of Bismuth for Dual-Modal Computed Tomography/Photoacoustic Imaging and Synergistic Thermoradiotherapy

Abstract: Multifunctional nanomaterials with integrated diagnostic and therapeutic functions, combination therapy to enhance treatment efficacy, as well as low toxicity have drawn tremendous attentions. Herein, we report a multifunctional theranostic agent based on peptide (LyP-1)-labeled ultrasmall semimetal nanoparticles of bismuth (Bi-LyP-1 NPs). Ultrasmall Bi NPs (3.6 nm) were facilely synthesized using oleylamine as the reducing agent and exhibited a higher tumor accumulation after being conjugated with the tumor-homing peptide LyP-1. The abilities to absorb both ionizing radiation and the second near-infrared (NIR-II) window laser radiation ensured that Bi-LyP-1 NPs are capable of dual-modal computed tomography/photoacoustic imaging and efficient synergistic NIR-II photothermal/radiotherapy of tumors. Moreover, Bi-LyP-1 NPs could be rapidly cleared from mice through both renal and fecal clearance and almost completely cleared after 30 days. Such multifunctional nanoparticles as efficient cancer theranostic ag...

Efficient Nanovaccine Delivery in Cancer Immunotherapy

Abstract: Vaccines hold tremendous potential for cancer immunotherapy by treating the immune system. Subunit vaccines, including molecular adjuvants and cancer-associated antigens or cancer-specific neoantigens, can elicit potent antitumor immunity. However, subunit vaccines have shown limited clinical benefit in cancer patients, which is in part attributed to inefficient vaccine delivery. In this Perspective, we discuss vaccine delivery by synthetic nanoparticles or naturally derived nanoparticles for cancer immunotherapy. Nanovaccines can efficiently codeliver adjuvants and multiepitope antigens into lymphoid organs and into antigen-presenting cells, and the intracellular release of vaccine and cross-presentation of antigens can be fine-tuned via nanovaccine engineering. Aside from peptide antigens, antigen-encoding mRNA for cancer immunotherapy delivered by nanovaccine will also be discussed.

Iron Oxide Nanoparticle Based Contrast Agents for Magnetic Resonance Imaging.

Abstract: Magnetic iron oxide nanoparticles (MIONs) have attracted enormous attention due to their wide applications, including for magnetic separation, for magnetic hyperthermia, and as contrast agents for magnetic resonance imaging (MRI). This review article introduces the methods of synthesizing MIONs, and their application as MRI contrast agents. Currently, many methods have been reported for the synthesis of MIONs. Herein, we only focus on the liquid-based synthesis methods including aqueous phase methods and organic phase methods. In addition, the MIONs larger than 10 nm can be used as negative contrast agents and the recently emerged extremely small MIONs (ES-MIONs) smaller than 5 nm are potential positive contrast agents. In this review, we focus on the ES-MIONs because ES-MIONs avoid the disadvantages of MION-based T2- and gadolinium chelate-based T1-weighted contrast agents.

Albumin/vaccine nanocomplexes that assemble in vivo for combination cancer immunotherapy.

Abstract: Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+ cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.

Tumor Microenvironment-Triggered Supramolecular System as an In Situ Nanotheranostic Generator for Cancer Phototherapy.

Abstract: The efficacy of photosensitizers in cancer phototherapy is often limited by photobleaching, low tumor selectivity, and tumor hypoxia. Assembling photosensitizers into nanostructures can improve photodynamic therapy efficacy and the safety profile of photosensitizers. Herein by employing supramolecular assembly, enhanced theranostic capability of Mn2+-assisted assembly of a photosensitizer (sinoporphyrin sodium, DVDMS) is demonstrated. A tumor environment-triggered coassembly strategy is further developed to form Mn/DVDMS nanotheranostics (nanoDVD) for cancer phototherapy. MnO2 nanosheets serve as a highly effective DVDMS carrier and in situ oxygen and nanoDVD generator. In MCF-7 cells and xenograft tumors, MnO2/DVDMS is reduced by glutathione (GSH) and H2O2 and reassembled into nanoDVD, which can be monitored by activated magnetic resonance/fluorescence/photoacoustic signals. Intriguingly, the decrease of GSH, the production of O2, and the formation of nanoDVD are shown to be synergistic with phototherapy to improve antitumor efficacy in vitro and in vivo, offering a new avenue for cancer theranostics.

Multifunctional Theranostic Nanoparticles Based on Exceedingly Small Magnetic Iron Oxide Nanoparticles for T1-Weighted Magnetic Resonance Imaging and Chemotherapy

Abstract: The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (<5 nm) are promising T1-weighted contrast agents for magnetic resonance imaging (MRI) due to their good biocompatibility compared with Gd-chelates. However, the best particle size of ES-MIONs for T1 imaging is still unknown because the synthesis of ES-MIONs with precise size control to clarify the relationship between the r1 (or r2/r1) and the particle size remains a challenge. In this study, we synthesized ES-MIONs with seven different sizes below 5 nm and found that 3.6 nm is the best particle size for ES-MIONs to be utilized as T1-weighted MR contrast agent. To enhance tumor targetability of theranostic nanoparticles and reduce the nonspecific uptake of nanoparticles by normal healthy cells, we constructed a drug delivery system based on the 3.6 nm ES-MIONs for T1-weighted tumor imaging and chemotherapy. The laser scanning confocal microscopy (LSCM) and flow cytometry analysis results demonstrate that our strategy of p...

Core-Satellite Polydopamine-Gadolinium-Metallofullerene Nanotheranostics for Multimodal Imaging Guided Combination Cancer Therapy.

Abstract: Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.

Nanotechnology-Enhanced No-Wash Biosensors for in Vitro Diagnostics of Cancer.

Abstract: In vitro biosensors have been an integral component for early diagnosis of cancer in the clinic. Among them, no-wash biosensors, which only depend on the simple mixing of the signal generating probes and the sample solution without additional washing and separation steps, have been found to be particularly attractive. The outstanding advantages of facile, convenient, and rapid response of no-wash biosensors are especially suitable for point-of-care testing (POCT). One fast-growing field of no-wash biosensor design involves the usage of nanomaterials as signal amplification carriers or direct signal generating elements. The analytical capacity of no-wash biosensors with respect to sensitivity or limit of detection, specificity, stability, and multiplexing detection capacity is largely improved because of their large surface area, excellent optical, electrical, catalytic, and magnetic properties. This review provides a comprehensive overview of various nanomaterial-enhanced no-wash biosensing technologies a...

Antitumor Activity of a Unique Polymer That Incorporates a Fluorescent Self-Assembled Metallacycle

Abstract: Despite the well-known anticancer activity of mono- and multinuclear platinum complexes, studies of the antitumor performances of platinum-based supramolecular coordination complexes are rare. Herein, we report on the synthesis of a four-armed amphiphilic copolymer, Pt-PAZMB-b-POEGMA, containing a metallacycle M, in which the tetraphenylethene derivative acts as an aggregation-induced emissive fluorescent probe for live cell imaging and the 3,6-bis[trans-Pt(PEt3)2]phenanthrene (PhenPt) is an anticancer drug. This copolymer was further self-assembled into nanoparticles of different sizes and vesicles depending upon the experimental conditions. The impacts of the morphology and size of the assemblies on their endocytic pathways, uptake rates, internalization amounts, and cytotoxicities were investigated. The self-assemblies were further employed to encapsulate doxorubicin (DOX) to achieve a synergistic anticancer effect. Controlled drug release was also realized via amphiphilicity changes and was driven by ...

Biocompatible D–A Semiconducting Polymer Nanoparticle with Light-Harvesting Unit for Highly Effective Photoacoustic Imaging Guided Photothermal Therapy

Abstract: The development of nanotheranostic agents that integrate diagnosis and therapy for effective personalized precision medicine has obtained tremendous attention in the past few decades. In this report, biocompatible electron donor-acceptor conjugated semiconducting polymer nanoparticles (PPor-PEG NPs) with light-harvesting unit is prepared and developed for highly effective photoacoustic imaging guided photothermal therapy. To the best of our knowledge, it is the first time that the concept of light-harvesting unit is exploited for enhancing the photoacoustic signal and photothermal energy conversion in polymer-based theranostic agent. Combined with additional merits including donor-acceptor pair to favor electron transfer and fluorescence quenching effect after NP formation, the photothermal conversion efficiency of the PPor-PEG NPs is determined to be 62.3%, which is the highest value among reported polymer NPs. Moreover, the as-prepared PPor-PEG NP not only exhibits a remarkable cell-killing ability but also achieves 100% tumor elimination, demonstrating its excellent photothermal therapeutic efficacy. Finally, the as-prepared water-dispersible PPor-PEG NPs show good biocompatibility and biosafety, making them a promising candidate for future clinical applications in cancer theranostics.

Intertwining DNA-RNA nanocapsules loaded with tumor neoantigens as synergistic nanovaccines for cancer immunotherapy.

Abstract: Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs. CpG and shRNA in iDR-NCs synergistically activate APCs for sustained antigen presentation. Remarkably, iDR-NC/neoantigen nanovaccines elicit 8-fold more frequent neoantigen-specific peripheral CD8+ T cells than CpG, induce T cell memory, and significantly inhibit the progression of neoantigen-specific colorectal tumors. Collectively, iDR-NCs represent potential DNA/RNA/peptide triple-co-delivery nanocarriers and synergistic tumor immunotherapeutic nanovaccines.

Inhibiting Metastasis and Preventing Tumor Relapse by Triggering Host Immunity with Tumor-Targeted Photodynamic Therapy Using Photosensitizer-Loaded Functional Nanographenes

Abstract: Effective cancer therapy depends not only on destroying the primary tumor but also on conditioning the host immune system to recognize and eliminate residual tumor cells and prevent metastasis. In this study, a tumor integrin αvβ6-targeting peptide (the HK peptide)-functionalized graphene oxide (GO) was coated with a photosensitizer (HPPH). The resulting GO conjugate, GO(HPPH)-PEG-HK, was investigated whether it could destroy primary tumors and boost host antitumor immunity. We found that GO(HPPH)-PEG-HK exhibited significantly higher tumor uptake than GO(HPPH)-PEG and HPPH. Photodynamic therapy (PDT) using GO(HPPH)-PEG suppressed tumor growth in both subcutaneous and lung metastatic mouse models. Necrotic tumor cells caused by GO(HPPH)-PEG-HK PDT activated dendritic cells and significantly prevented tumor growth and lung metastasis by increasing the infiltration of cytotoxic CD8+ T lymphocytes within tumors as evidenced by in vivo optical and single-photon emission computed tomography (SPECT)/CT imaging....

Impact of Semiconducting Perylene Diimide Nanoparticle Size on Lymph Node Mapping and Cancer Imaging

Abstract: Semiconducting molecules of perylene diimide (PDI) with strong light absorption properties in the near-infrared region and good biocompatibility have received increasing attention in the field of theranostics, especially as photoacoustic (PA) imaging agents. Herein, we report a series of [64Cu]-labeled PDI nanoparticles (NPs) of different sizes (30, 60, 100, and 200 nm) as dual positron emission tomography (PET) and PA imaging probes and photothermal therapy agents. The precise size control of the PDI NPs can be achieved by adjusting the initial concentration of PDI molecules in the self-assembly process, and the photophysical property of different sized PDI NPs was studied in detail. Furthermore, we systematically investigated the size-dependent accumulation of the PDI NPs in the lymphatic system after local administration and in tumors after intravenous injection by PA and PET imaging. The results revealed that 100 nm is the best size for differentiating popliteal and sciatic LNs since the interval is a...

Transformative Nanomedicine of an Amphiphilic Camptothecin Prodrug for Long Circulation and High Tumor Uptake in Cancer Therapy.

Abstract: We report a camptothecin (CPT) prodrug that was well formulated in solution and rapidly transformed into long-circulating nanocomplexes in vivo for highly efficient drug delivery and effective cancer therapy. Specifically, using a redox-responsive disulfide linker, CPT was conjugated with an albumin-binding Evans blue (EB) derivative; the resulting amphiphilic CPT-ss-EB prodrug self-assembled into nanostructures in aqueous solution, thus conferring high solubility and stability. By binding CPT-ss-EB to endogenous albumin, the 80 nm CPT-ss-EB nanoparticles rapidly transformed into 7 nm albumin/prodrug nanocomplexes. CPT-ss-EB was efficient at intracellular delivery into cancer cells, released intact CPT in a redox-responsive manner, and exhibited cytotoxicity as potent as CPT. In mice, the albumin/CPT-ss-EB nanocomplex exhibited remarkably long blood circulation (130-fold greater than CPT) and efficient tumor accumulation (30-fold of CPT), which consequently contributed to excellent therapeutic efficacy. O...

Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy

Abstract: The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli. In this manner, the system enables glucose-responsive and closed-loop release to significantly improve Ex4 therapeutic performance. Moreover, integration of mineralized particles can enhance the mechanical strength of alginate-based MN by crosslinking to facilitate skin penetration, thus supporting painless and non-invasive transdermal administration. We believe this smart glucose-responsive Ex4 delivery holds great promise for type 2 diabetes therapy by providing safe, long-term, and on-demand Ex4 therapy.

Rational Design of Branched Nanoporous Gold Nanoshells with Enhanced Physico-Optical Properties for Optical Imaging and Cancer Therapy.

Abstract: Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au3+). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacous...