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Journal ArticleDOI: 10.1039/D0NR08440A

Glutathione-depleting nanoplatelets for enhanced sonodynamic cancer therapy.

04 Mar 2021-Nanoscale (Royal Society of Chemistry (RSC))-Vol. 13, Iss: 8, pp 4512-4518
Abstract: In combating cancer, ultrasound (US)-triggered sonodynamic therapy (SDT) manifests a wide range of promising applications as a noninvasive treatment modality, thus showing potential to overcome the shortcomings and disadvantages of conventional photodynamic therapy (PDT). Reactive oxygen species (ROS)-based therapy is practically destroyed by the high concentration of glutathione (GSH) inside tumors, and depleting GSH to improve the outcome of SDT is indeed a great challenge. Herein, we designed GSH-depleting nanoplatelets for enhanced sonodynamic cancer therapy. A platelet membrane coated nanosystem (PSCI) has been designed and tested comprising mesoporous silica nanoparticles (MSNs) which have been loaded with cinnamaldehyde (CA) as an oxidative stress amplifier. The inner layer comprises the sonosensitizer IR780 and the oxidative stress amplifier CA, whereas the platelet membranes (PM) were designed and utilized as an outer layer that can target tumors, thereby enhancing the effectiveness of SDT by attenuating the capability of tumor cells for scavenging ROS with GSH. SDT and cinnamaldehyde amplify oxidative stress by acting synergistically, leading to the preferential destruction of cancer cells in vitro and in vivo. It is hoped that next-generation tumor SDT treatments will find their way with the help of this strategy.

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Topics: Sonodynamic therapy (63%)
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11 results found


Journal ArticleDOI: 10.1016/J.NANTOD.2021.101170
Xianwen Wang1, Xiyu Wang1, Qingfen Yue2, Huizhong Xu1  +8 moreInstitutions (2)
01 Aug 2021-Nano Today
Abstract: Ultrasound (US)-activated sonodynamic therapy (SDT), as a non-invasive therapy method, has the advantages of large tissue penetration depth promising for treatment of large internal tumors. However, due to the hypoxic characteristic of tumor microenvironment and lack of effective sonosensitizers, the efficacy of SDT is still not satisfactory. In addition, there is still a lot of space for the exploration of SDT-based collaborative cancer treatment. Herein, ultra-small titanium nitride (TiN) nanodots are successfully synthesized for photothermal-enhanced SDT against cancer. Ultra-small TiN nanodots with an average size of 1.5 nm are prepared by the liquid exfoliation method. The obtained TiN nanodots have satisfactory second near-infrared (NIR II) absorption, which can be used for photoacoustic (PA) imaging and photothermal therapy (PTT) of tumors. Interestingly, TiN nanodots can also be used as efficient sonosensitizers to generate reactive oxygen species (ROS) under US irradiation owing to the special defect structure and surface partial oxidation to TiO2 for sonodynamic cancer therapy. The mild photothermal heating of tumors generated by TiN nanodots under NIR II laser irradiation can facilitate intra-tumoral blood flow and improve tumor oxygenation, thereby achieving a significant synergistic treatment effect by combining PTT and SDT. Importantly, most of these TiN nanodots due to their ultra-small size can be promptly metabolized from the mouse body, thus avoiding the concerns about long-term toxicity of nanomaterials. Our work thus for the first time demonstrates the potential use of metal nitride nanomaterials as a new type of multifunctional nano-agents with intriguing properties for cancer theranostic applications.

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11 Citations


Journal ArticleDOI: 10.1021/ACSNANO.1C00498
Xiaotong Cheng1, Hai-Dong Xu1, Huan-Huan Ran1, Gaolin Liang1  +1 moreInstitutions (1)
11 May 2021-ACS Nano
Abstract: Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, and solid evidence has corroborated the resulting tumor resistance to a variety of anticancer therapies, suggesting that this biochemical characteristic of cancer cells can be developed as a potential target for cancer treatments. The single treatment of GSH-depleting agents can potentiate the responses of the cancer cells to different cell death stimuli; therefore, as an adjunctive strategy, GSH depletion is usually combined with mainstream cancer therapies for enhancing the therapeutic outcomes. Propelled by the rapid development of nanotechnology, GSH-depleting agents can be readily constructed into anticancer nanomedicines, which have shown a steep rise over the past decade. Here, we review the common GSH-depleting nanomedicines which have been widely applied in synergistic cancer treatments in recent years. Some current challenges and future perspectives for GSH depletion-based cancer therapies are also presented. With the understanding of the structure-property relationship and action mechanisms of these biomaterials, we hope that the GSH-depleting nanotechnology will be further developed to realize more effective disease treatments and even achieve successful clinical translations.

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Topics: Cancer (54%)

11 Citations


Open accessJournal ArticleDOI: 10.3390/PHARMACEUTICS13071067
Elham Rastegari1, Elham Rastegari2, Yu Jer Hsiao1, Wei Yi Lai1  +11 moreInstitutions (4)
12 Jul 2021-Pharmaceutics
Abstract: The efficient and safe delivery of therapeutic drugs, proteins, and nucleic acids are essential for meaningful therapeutic benefits. The field of nanomedicine shows promising implications in the development of therapeutics by delivering diagnostic and therapeutic compounds. Nanomedicine development has led to significant advances in the design and engineering of nanocarrier systems with supra-molecular structures. Smart mesoporous silica nanoparticles (MSNs), with excellent biocompatibility, tunable physicochemical properties, and site-specific functionalization, offer efficient and high loading capacity as well as robust and targeted delivery of a variety of payloads in a controlled fashion. Such unique nanocarriers should have great potential for challenging biomedical applications, such as tissue engineering, bioimaging techniques, stem cell research, and cancer therapies. However, in vivo applications of these nanocarriers should be further validated before clinical translation. To this end, this review begins with a brief introduction of MSNs properties, targeted drug delivery, and controlled release with a particular emphasis on their most recent diagnostic and therapeutic applications.

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Topics: Nanocarriers (56%), Targeted drug delivery (55%), Nanomedicine (55%)

5 Citations


Open accessJournal ArticleDOI: 10.1186/S12951-021-01094-X
Guoyun Wan1, Xuheng Chen1, Hai-Jiao Wang1, Shenglei Hou2  +7 moreInstitutions (3)
Abstract: Background Colorectal cancer is known to be resistant to immune checkpoint blockade (ICB) therapy. Sonodynamic therapy (SDT) has been reported to improve the efficacy of immunotherapy by inducing immunogenic cell death (ICD) of cancer. However, the SDT efficacy is extremely limited by Nrf2-based natural redox balance regulation pathway in cancer cells in response to the increased contents of reactive oxygen species (ROS). Nuclear-targeting strategy has shown unique advantages in tumor therapy by directly destroying the DNA. Thus it can be seen that Nrf2-siRNA augmented nuclear-targeting SDT could boost ICB therapy against colorectal cancer.

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Topics: Sonodynamic therapy (61%), Cancer (56%), Immunogenic cell death (54%) ... show more

Journal ArticleDOI: 10.1016/J.BIOMATERIALS.2021.121063
Wen Li1, Yilin Song1, Xiaoyang Liang1, Yue Zhou1  +4 moreInstitutions (1)
09 Aug 2021-Biomaterials
Abstract: Rheumatoid arthritis (RA) is an autoimmune disease associated with synovitis and cartilage destruction. Ultrasound (US)-driven sonodynamic therapy (SDT) possess a good application prospect in RA therapy because of its non-invasiveness and strong tissue penetration capabilities, which can kill activated synovial inflammatory cells. Nevertheless, the tiny accumulation of sonosensitizers in the joints and the hypoxic synovial microenvironment severely limit the therapeutic effect of SDT. Hence, we developed a sonosensitizer spafloxacin (SPX) doped and human serum albumin (HSA) loaded concave-cubic rhodium (Rh) nanozyme (Rh/SPX-HSA) to realize mutual-reinforcing SDT during ultrasonic activation. On the one hand, SPX would cause mitochondrial dysfunction by inducing excessive reactive oxygen species (ROS) production, thus suppressing fibroblast-like synoviocyte (FLS) under US conditions. On the other hand, concave-cubic rhodium was utilized as a nanozyme with endogenous peroxidase (POD) and catalase (CAT)-like enzyme activities, which not only relieved the hypoxia of the joint to resist angiogenesis, but also enormously ascended the SDT efficacy by rising 1O2 levels. Interestingly, the activity of nanozymes was also improved by the ultrasonic cavitation effect, thereby realizing mutual-reinforcing SDT. Overall, our strategy provided Rh-based to achieve effective SDT under hypoxic microenvironment, which offered a promising prospect for highly efficient treatment of RA.

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Topics: Sonodynamic therapy (56%)

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35 results found


Journal ArticleDOI: 10.1038/NRC1549
Abstract: Head and neck squamous-cell carcinoma (HNSCC) is the sixth most common cancer worldwide and, disappointingly, survival rates are not improving. Moreover, HNSCC has a severe impact on the quality of life of patients and survivors, and the significant morbidity subsequent to treatment often mandates long-term multidisciplinary care, which places significant financial pressures on the treating institution. Therefore, prevention and early diagnosis of high-risk pre-malignant lesions are high priorities for reducing deaths due to head and neck cancer. Recent advances have begun to elucidate the different aetiologies of HNSCCs in relation to previous pre-malignancies and to identify which pre-malignant lesions are likely to progress to malignancy.

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Topics: Head and neck cancer (52%)

402 Citations


Open accessJournal ArticleDOI: 10.1021/JACS.8B01072
Guangxu Lan, Kaiyuan Ni, Ziwan Xu1, Samuel S. Veroneau  +2 moreInstitutions (1)
Abstract: Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal–organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron-oxo clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions. Fe-TBP mediated PDT significantly improved the efficacy of anti-programmed death-ligand 1 (α-PD-L1) treatment and elicited abscopal effects in a mouse model of colorectal cancer, resulting in >90% regression of tumors. Mechanistic studies revealed that Fe-TBP mediated PDT induced significant tumor infiltration of cytotoxic T cells.

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Topics: Tumor hypoxia (55%), Cancer immunotherapy (54%), Immunotherapy (53%) ... show more

339 Citations


Journal ArticleDOI: 10.1021/JACS.6B11846
Ping Huang1, Xiaoqin Qian2, Yu Chen3, Luodan Yu3  +4 moreInstitutions (3)
Abstract: Traditional photodynamic therapy (PDT) suffers from the critical issues of low tissue-penetrating depth of light and potential phototoxicity, which are expected to be solved by developing new dynamic therapy-based therapeutic modalities such as sonodynamic therapy (SDT). In this work, we report on the design/fabrication of a high-performance multifunctional nanoparticulate sonosensitizer for efficient in vivo magnetic resonance imaging (MRI)-guided SDT against cancer. The developed approach takes the structural and compositional features of mesoporous organosilica-based nanosystems for the fabrication of sonosensitizers with intriguing theranostic performance. The well-defined mesoporosity facilitates the high loading of organic sonosensitizers (protoporphyrin, PpIX) and further chelating of paramagnetic transitional metal Mn ions based on metalloporphyrin chemistry (MnPpIX). The mesoporous structure of large surface area also maximizes the accessibility of water molecules to the encapsulated paramagnetic...

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Topics: Sonodynamic therapy (59%)

338 Citations


Journal ArticleDOI: 10.1021/ACS.NANOLETT.9B01595
Shuang Liang1, Xiaoran Deng1, Yun Chang1, Chunqiang Sun1  +12 moreInstitutions (2)
17 May 2019-Nano Letters
Abstract: As a noninvasive treatment modality, ultrasound (US)-triggered sonodynamic therapy (SDT) shows broad and promising applications to overcome the drawbacks of traditional photodynamic therapy (PDT) in combating cancer. However, the SDT efficacy is still not satisfactory without oxygen (O2) assistance. In addition, there is also much space to explore the SDT-based synergistic therapeutic modalities. Herein, a novel Pt-CuS Janus composed of hollow semiconductor CuS and noble metallic Pt was rationally designed and successfully synthesized. The hollow CuS shows a large inner cavity for loading sonosensitizer molecules (tetra-(4-aminophenyl) porphyrin, TAPP) to implement SDT. Moreover, the deposition of Pt not only enhances photothermal performance compared with those of CuS nanoparticles (NPs) due to the effect of the local electric field enhancement but also possesses nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce O2 that can overcome tumor hypoxia and augment the SDT-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated heat of Pt-CuS by 808 nm laser irradiation can accelerate the catalytic activity of Pt and elevate the O2 level that further facilitates SDT efficacy. Interestingly, the thermally sensitive copolymer coated around the Janus can act as a smart switch to regulate the catalytic ability of Pt and control TAPP release that has a significant effect on modulating the therapeutic effect. The synergistic catalysis-enhanced SDT efficiency and highly photothermal effect almost realized complete tumor resection without obvious reoccurrence and simultaneously displayed a highly therapeutic biosafety. Furthermore, the high optical absorbance allows the as-synthesized Pt-CuS Janus for photoacoustic (PA) imaging and NIR thermal imaging. This work develops a versatile nanoplatform for a multifunctional theranostic strategy and broadens the biological applications by rationally designing their structure.

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166 Citations


Journal ArticleDOI: 10.1002/ADMA.201706831
Duo Mao1, Fang Hu1, Kenry1, Shenglu Ji2  +4 moreInstitutions (2)
05 Mar 2018-Advanced Materials
Abstract: Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla). After intravenous injection, MIL-100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2 O2 inflammatory environment, releasing d-AzAla in the process. d-AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO-Cy5. Ultrasmall photosensitizer NPs with aggregation-induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal-organic-framework-assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.

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161 Citations