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BIOMATERIALS · 2018 · IF 8.806

Biomimetic O2-Evolving metal-organic framework nanoplatform for highly efficient photodynamic therapy against hypoxic tumor

Shutao Gao,Pengli Zheng,Zhenhua Li,Xiaochen Feng,Weixiao Yan,Shizhu Chen,Weisheng Guo,Dandan Liu,Xinjian Yang,Shuxiang Wang,Xing-Jie Liang,Jinchao Zhang

Improving the supply of O 2 and the circulation lifetime of photosensitizers for photodynamic therapy (PDT) in vivo would be a promising approach to eliminate hypoxic tumors. Herein, by taking advantage of the significant gas-adsorption capability of metal-organic frameworks (MOFs), a biomimetic O 2 -evolving photodynamic therapy (PDT) nanoplatform with long circulating properties was fabricated. Zirconium (IV)-based MOF (UiO-66) was used as a vehicle for O 2 storing, then conjugated with indocyanine green (ICG) by coordination reaction, and further coated with red blood cell (RBC) membranes. Upon 808 nm laser irradiation , the initial singlet oxygen ( 1 O 2 ) generated by ICG would decompose RBC membranes. At the same time, The photothermal property of ICG could facilitate the burst release of O 2 from UiO-66. Subsequently, the generated O 2 could significantly improve the PDT effects on hypoxic tumor. Owing to the advantages of long circulation and O 2 self-sufficient, the designed nanotherapeutic agent can improve the efficiency of treatment against hypoxia tumor via PDT. Hence, this study presents a new paradigm for co-delivery of O 2 and photosensitizers, and provides a new avenue to eliminate hypoxic tumors.

研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 材料科学
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MATERIALS & DESIGN · 2022 · IF 9.417

Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies

Pengcheng Hu,Wenjun Wang,Jingyun Sha,Yujuan Xing,Yong Wang,Changyu Wu,Jingjing Li,Kai Gao,Haicui Dong,Shaohui Zheng

Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administration. Herein, to address this issue, injectable and TME-responsive nanocomposite hydrogels were developed for localized and synergistic cancer therapy. The nanocomposite hydrogels (Au NBPs&Pt [email protected] gel) were synthesized via the formation of metal-sulfur bonds between 4arm-PEG-thiol and Au nanobipyramids or Pt nanoclusters with the DOX encapsulation. The hydrogel exhibited rapid gelation and excellent injectability. Attributed to the high absorbance of Au NBPs, the nanocomposite hydrogels revealed superior photothermal effect under NIR irradiation, which the DOX release was also regulated by NIR laser. In addition, the catalase- and peroxidase-like activities of Pt NCs were validated to convert endogenous H 2 O 2 into ROS and O 2 in situ to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Simultaneously, catalytic therapy combined with NIR irradiation exhibited strongest inhibition to the growth of 4T1 tumor in vitro and in vivo . Thus, this study provided a new strategy for TME remodeling and local combination therapies of different therapeutic agents.

CAS / MDL: 112-02-7 57-09-0
研究领域: 纳米医学 · 癌症治疗 · 材料科学 · 生物医学工程
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Curcumin-loaded mesoporous polydopamine nanoparticles modified by quaternized chitosan against bacterial infection through synergistic effect

Xiao Han,Weijia Gao,Zhe Zhou,Yongli Li,Duo Sun,Heyi Gong,Mengyuan Jiang,Yulu Gan,Xin Fang,Yuanzheng Qi,Junjie Jiao,Jinghui Zhao

Clinically, open wounds caused by accidental trauma and surgical lesion resection are easily infected by external bacteria, hindering wound healing. Antibacterial photodynamic therapy has become a promising treatment strategy for wound infection. In this study, a novel antibacterial nanocomposite material (QMC NPs) was synthesized by curcumin, quaternized chitosan and mesoporous polydopamine nanoparticles. The results showed that 150 μg/mL QMC NPs had good biocompatibility and exerted excellent antibacterial activity against Staphylococcus aureus and Escherichia coli after blue laser irradiation (450 nm, 1 W/cm 2 ). In vivo, QMC NPs effectively treated bacterial infection and accelerated the healing of infected wounds in mice.

研究领域: 纳米技术 · 生物医学工程 · 药学 · 微生物学 · 伤口愈合
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Nano Research · 2022 ·Vol. 15 ·期 4 ·3422-3433 · IF 10.269

Synergetic lethal energy depletion initiated by cancer cell membrane camouflaged nano-inhibitor for cancer therapy

Dong Fudan,Jiang Qikun,Li Lingxiao,Liu Tian,Zuo Shiyi,Gao Lin,Fang Mengna,Gao Yanlin,Sun Bingjun,Luo Cong,He Zhonggui,Sun Jin

Mitochondrial bioenergy plays a vital role in the occurrence and development of cancer. Although strategies to impede mitochondrial energy supply have been rapidly developed, the anticancer efficacy is still far from satisfactory, mainly attributed to the hybrid metabolic pathways of mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. Herein, we construct a cancer cell membrane camouflaged nano-inhibitor, mTPPa-Sy nanoparticle (NP), which co-encapsulates OXPHOS inhibitor (mitochondrial-targeting photosensitizers: TPPa) and glycolysis inhibitor (syrosingopine (Sy)) for synergistically blocking the two different energy pathways. The mTPPa-Sy NPs exhibit precision tumor-targeting due to the high affinity between the biomimic membrane and the homotypic cancer cells. Under laser irradiation, the mitochondrial-targeting TPPa, which is synthesized by conjugating pyropheophorbide a (PPa) with triphenylphosphin, produces excessive reactive oxygen species (ROS) and further disrupts the OXPHOS. Interestingly, OXPHOS inhibition reduces O 2 consumption and improves ROS production, further constructing a closed-loop OXPHOS inhibition system. Moreover, TPPa-initiated OXPHOS inhibition in combination with the Sy-triggered glycolysis inhibition results in lethal energy depletion, significantly suppressing tumor growth even after a single treatment. Our findings highlight the necessity and effectiveness of synergetic lethal energy depletion, providing a prospective strategy for efficient cancer therapy.

研究领域: 癌症生物学 · 纳米技术 · 治疗学 · 生物化学 · 药理学
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INORGANIC CHEMISTRY COMMUNICATIONS · 2025 · IF 5.4

Iridium oxide nanoparticles anchored on metal-organic framework for enhanced photodynamic and photothermal synergistic antibacterial activity

Yapu Yang,Yalin Chang,Yueshang Wang,Yinuo Gai,Jun Ma,Pengfei Shi

Phototherapy is rapidly evolving in the treatment of bacterial infections to counter the dangers of bacterial evolution and the development of bacterial resistance due to the misuse of antibiotics. Herein, we report a nano-antimicrobial platform (PCN-224-IrO 2 -HA), constructed by iridium oxide nanoparticles and metal-organic framework PCN-224. PCN-224-IrO 2 -HA is capable of the photodynamic therapy (PDT), which can induce bacterial death by converting surrounding O 2 to reactive oxygen species under laser irradiation. Meanwhile, IrO 2 can catalyse the decomposition of H 2 O 2 to generate O 2 and enhance PDT. Meanwhile, IrO 2 can rapidly convert light energy into thermal energy under laser irradiation, so that it is able to kill bacteria by photothermal therapy (PTT). Photodynamic therapy synergised with photothermal therapy significantly inhibit the growth of bacteria, providing a new idea for phototherapy to treat bacterial infections.

CAS / MDL: 65-85-0 9067-32-7
研究领域: 纳米医学 · 抗菌治疗 · 光疗 · 材料科学 · 传染病
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2024 · IF 9.4

Glutathione-depleting polyprodrug nanoparticle for enhanced photodynamic therapy and cascaded locoregional chemotherapy

Xinlu Zhang,Xu Zhang,Shutong Chen,Yongxin Liu,Chen Cao,Guohui Cheng,Sheng Wang

Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy.

CAS / MDL: 78-67-1
研究领域: 纳米技术 · 药学 · 癌症研究 · 治疗学
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CHEMISTRY OF MATERIALS · 2017 · IF 9.466

Dual-Targeted Cascade-Responsive Prodrug Micelle System for Tumor Therapy in Vivo

Liangliang Dai,Ruisi Cai,Menghuan Li,Zhong Luo,Yonglin Yu,Weizhen Chen,Xinkun Shen,Yuxia Pei,Xiaojing Zhao,Kaiyong Cai

This study reports a cascade-responsive disassemble micellar drug delivery system with dual-targeting potential (cell and mitochondria targeting), which optimizes the distribution of antitumor drugs on systemic, local, and subcellular levels to enhance antitumor efficacy. A new cationic porphyrin derivative 5-(3-hydroxy-p-(4-trimethylammonium)butoxyphenyl)-10,15,20-triphenylporphyrin chlorine (MTPP) is synthesized as a mitochondria-targeting photosensitizer. After accumulating at a tumor site, the micellar nanosystem is endocytosed by tumor cells facilitated by the folate receptor-mediated pathway. Then, the hydrophobic PDEA block would be protonated in intracellular acidic endo-/lysosomes and promote the escape of prodrug micelles from endo-/lysosome to cytoplasm, resulting in the first-stage destabilization of micelles. Subsequently, the CPT is released in response to high concentration of GSH in cytoplasm, which would greatly increase the hydrophilicity of the BOH block and initiate the complete disassembly of the polymer micelles owing to the damage of the hydrophilic–hydrophobic balance. Additionally, the released MTPP is selectively accumulated in mitochondria and activates mitochondria apoptotic pathway upon light irradiation as a result of ROS generation. Both in vitro and in vivo studies indicate that the polymeric micelle not only effectively improves the targeted delivery efficiency but also dramatically enhances the combinational antitumor efficacy while reducing the side effects associated with the laser irradiation and mitochondria-targeted tumor therapy.

研究领域: 药学 · 纳米技术 · 癌症治疗 · 药物递送系统
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JOURNAL OF APPLIED POLYMER SCIENCE · 2022 ·Vol. 139 ·期 27 ·e52444 · IF 3.057

Fabrication of novel PNIPAM@GO microspheres loaded with dual drugs featuring on-demand drug release capability

Yulin Jiang,Jing Wang,Juehan Wang,Yi Zhuang,Lin Qi,Ganjun Feng,Li Zhang

In this research, we successfully prepared a new kind of core-shell microspheres (PNIPAM@GO) composed of hydrophilic poly (N-isopropyl acrylamide) (PNIPAM) nanoparticles as the core and amphiphilic graphene oxide (GO) nanosheets as the shell through hydrogen bonding and self-assembly in organic solvent. The temperature-sensitive behavior of the PNIPAM core made its average size decrease from 888.3 nm to 630.3 nm with temperature increasing from 25°C to 50°C. And the GO shell could give PNIPAM@GO microspheres remarkable photothermal effects in water under NIR laser irradiation (808 nm) for 20 min. Further, doxorubicin (DOX) and 5-fluorouracil (5-FU) were loaded into the core and the shell with loading efficiency of 81% and 11%, respectively. By turning on/off NIR irradiation, the PNIPAM@GO microspheres could respond to the heat generated from GO shell by volume shrinkage, thus on-demand controlling the drug release. The in vitro biological assessment verified that the samples prepared here were biocompatible. The developed platform shows a potential application in chemo-photothermal therapy of cancers in the future.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 药学 · 癌症治疗
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RSC Advances · 2023 ·Vol. 13 ·期 16 ·11215-11224 · IF 3.9

Aptamer modified Zr-based porphyrinic nanoscale metal–organic frameworks for active-targeted chemo-photodynamic therapy of tumors

Haidi Feng,Lu Zhao,Zhiqiang Bai,Zhihui Xin,Chaoyu Wang,Lizhen Liu,Jinping Song,Haifei Zhang,Yunfeng Bai,Feng Feng

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic 1O2 for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. In vitro, experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.

CAS / MDL: 65-85-0 13520-92-8
研究领域: 纳米技术 · 癌症治疗 · 材料科学 · 生物医学工程
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International Journal of Nanomedicine · 2020 · IF 5.115

Self-Assembled Dual-Targeted Epirubicin-Hybrid Polydopamine Nanoparticles for Combined Chemo-Photothermal Therapy of Triple-Negative Breast Cancer

Xiang Li,Qian Zou,Jing Zhang,Peng Zhang,Xiong Zhou,Satya Siva Kishan Yalamarty,Xinli Liang,Yali Liu,Qin Zheng,Jianqing Gao

Purpose Folic acid and cyclic arginylglycylaspartic acid peptides were introduced to the surface of negatively charged lipid-coated hybrid polydopamine-cysteine cores for the delivery of epirubicin (EPI) (E/PCF-NPs). The combined chemo-photothermal therapy using E/PCF-NPs for triple-negative breast cancer was evaluated. Materials and Methods The temperature elevation and thermal toxicity of nanoparticles were studied. The morphology and properties of E/PCF-NPs were characterized by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. Physicochemical properties, including particle size, zeta potential, drug loading, entrapment efficiency (EE%), stability and in vitro release, were determined. The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD + /NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. Pharmacokinetic studies and tissue distributions were performed and detected by an ultra-high performance liquid chromatography/mass spectrometry system. The antitumor effects of E/PCF-NPs under near-infrared (NIR) laser irradiation were also evaluated. Results The sphere-like morphology of E/PCF-NPs showed a high EE%, uniform size of 106.7 nm, remarkable stability, and highly improved cytotoxicity under NIR laser, when compared to that of photothermal treatment alone. In vitro release of EPI from E/PCF-NPs was pH sensitive, and a greater response was achieved under NIR laser irradiation. Compared to chemotherapy or photothermal treatment alone, the combined treatment in vitro significantly inhibited the survival rate of 4T1 cells to 17.7%, induced ROS generation, and reduced NAD + /NADH significantly. Treatment with E/PCF-NPs under irradiation induced 4T1 cell apoptosis in approximately 93.6% cells. In vitro cellular uptake of E/PCF-NPs was time-dependent. The long-circulating and higher tumor accumulation of E/PCF-NPs resulted in complete ablation of breast tumor tissue through the enhanced photothermal effect by NIR laser irradiation-mediated cell apoptosis. Conclusion E/PCF-NPs show enhanced anti-cancer effects due to synergistic effects of chemotherapy with photothermal therapy and may be potential therapeutic agents for cancer treatment.

CAS / MDL: 62-31-7
研究领域: 肿瘤学 · 纳米技术 · 药学 · 生物医学工程
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CHEMISTRY OF MATERIALS · 2020 · IF 9.567

Biofilm-Responsive Polymeric Nanoparticles with Self-Adaptive Deep Penetration for In Vivo Photothermal Treatment of Implant Infection

Congyu Wang,Wei Zhao,Bing Cao,Zhixiong Wang,Qi Zhou,Siyu Lu,Ligong Lu,Meixiao Zhan,Xianglong Hu

Biofilm can protect bacteria from immune attacks and antibiotic inhibition, and bacterial biofilm hosted in implanted materials and medical devices is a serious threat for modern medical system. Herein, we report biofilm-responsive caged guanidine nanoparticles (CGNs) to deeply penetrate and accumulate in bacterial biofilm, and then efficient photothermal eradication of bacterial biofilm is achieved upon NIR laser irradiation via the proof-of-concept formulation of photothermal agents in CGNs. In physiological conditions and blood circulation, CGNs are negatively charged by masking the positive charge of guanidine via covalent modification with acid-cleavable moieties, exhibiting high biocompatibility and minimal hemolysis. Whereas upon blood circulation and passive accumulation at infected implant sites, CGNs are self-adaptive in acidic biofilm to release the protective caging group and expose native guanidine moieties, which can promote nanoparticle deep biofilm penetration and bacteria adhesion as well as membrane fusion. After that, remarkable photothermal effect with a high photothermal conversion efficiency of ∼40.9% can eradicate implant biofilm upon NIR laser irradiation. It can efficiently treat S. aureus biofilm-infected implant catheters in vivo via only one single treatment in a mouse model, exhibiting ∼99.6% bacteria inhibition ratio. Apart from this proof-of-concept work, current guanidine-caged biofilm responsive polymeric nanoparticles are promising general vectors to treat biofilm and resistant pathogens in medicine and daily healthcare.

CAS / MDL: 766-39-2 108-30-5
研究领域: 生物材料 · 纳米医学 · 传染病 · 生物医学工程
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NANOTECHNOLOGY · 2020 ·Vol. 31 ·期 19 ·195103 · IF 3.551

Doxorubicin-loaded pH-responsive nanoparticles coated with chlorin e6 for drug delivery and synergetic chemo-photodynamic therapy

Junlong Liang,Xiaokang Jin,Biling Chen,Jinhua Hu,Qianwei Huang,Junmin Wan,Zhiwen Hu,Bing Wang

The integration of chemotherapy drugs and photosensitizers to form versatile nanoplatforms for achieving chemo-photodynamic synergetic therapy has shown great superiority in tumor theranostic applications. We constructed pH-responsive nanoparticles (DOX/PB NPs) encapsulating the chemotherapeutic drug doxorubicin (DOX) into the cores of PLGA NPs coated with bovine serum albumin (BSA) via a water-in-oil (W/O/W) emulsion method. A simple and efficient chemo-photodynamic synergetic nanoplatform (DOX/PB@Ce6 NPs) was obtained by the adsorption of photosensitizer chlorin e6 (Ce6) onto the surface of the DOX/PB NPs. With optimal size, pH-responsive drug release behavior and excellent singlet oxygen production, the DOX/PB@Ce6 NPs have the potential to enhance anti-tumor efficiency. The cellular uptake, cytotoxicity, chemo-photodynamic synergetic effect and biocompatibility of the NPs were evaluated based on HeLa cells via in vitro experiments. The in vitro chemo-photodynamic synergetic experiments indicated that the DOX/PB@Ce6 NPs had remarkable cancer cell killing efficiency under laser irradiation. Notably, by hemolysis assay, all the NPs displayed excellent blood compatibility and were expected to be applicable for intravenous injection. In summary, the designed DOX/PB@Ce6 NPs multifunctional theranostic nanoplatform had excellent reactive oxygen species generation and would be a potential therapeutic platform for chemo-photodynamic synergetic therapy.

CAS / MDL: 26780-50-7
研究领域: 纳米技术 · 药学 · 癌症研究 · 生物医学工程 · 诊疗学
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