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CHEMICAL ENGINEERING JOURNAL · 2022 · IF 16.744

Biodegradable copper telluride nanosheets for redox-homeostasis breaking-assisted chemodynamic cancer therapy boosted by mild-photothermal effect

Guangzhi Zhou,Ming Li

Chemodynamic therapy (CDT) holds great promise for cancer treatment through employing the Fenton or Fenton-like effects for highly toxic ·OH production exclusively in the tumor microenvironment. Herein, glutathione (GSH)-degradable Cu 2-x Te nanosheets modified with polyethylene glycol (bioCu 2-x Te NSs) as a multifunctional CDT agent are reported for effective cancer treatment via mild-photothermally enhanced CDT. The resulting bioCu 2-x Te NSs exhibit excellent near-infrared II (NIR-II) plasmonic absorption and photothermal properties. Upon endocytosis by cancer cells, bioCu 2-x Te NSs are degraded into Cu + and elemental Te by GSH overexpressed in cancer cells. The generated Cu + and Te together exhibit efficient catalytic decomposition of endogenous H 2 O 2 into ·OH with effective GSH depletion and redox homeostasis breaking of cancer cells. The mild-photothermal effect from the NIR-II irradiation is confirmed to promote intracellular ·OH production and tumor accumulation of bioCu 2-x Te NSs. Owing to all these prominent features, our results on both in vitro and in vivo studies verify the remarkable therapeutic efficacy via mild-photothermally enhanced CDT on a MCF-7 tumor mouse model with intravenous administration of bioCu 2-x Te NSs under NIR-II irradiation. This study demonstrates the potential of bioCu 2-x Te NSs as a potent CDT agent, which features GSH-triggered degradability and excellent therapeutic functions, for efficient cancer treatment.

研究领域: 纳米技术 · 癌症治疗 · 生物医学工程 · 材料科学
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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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BIOSENSORS & BIOELECTRONICS · 2016 · IF 7.476

Multienzyme decorated polysaccharide amplified electrogenerated chemiluminescence biosensor for cytosensing and cell surface carbohydrate profiling

Ling Zhang,Yangzhong Wang,Qianqian Tian,Yang Liu,Jinghong Li

A novel ECL biosensor for cytosensing and cell surface carbohydrate expression evaluation was developed, by the integration of the peptide modified interface for highly specific carbohydrate recognition and sodium alginate loaded glucose oxidase as the signal probe with high signal amplification efficiency. A cysteine-terminated peptide self-assembled on the electrode through Au–S bond to construct a functional interface for cell capture, with decent biocompatibility and high affinity for the human breast cancer cell MCF-7. Concanavalin A lectin modified gold nanoparticles specifically recognized the cell surface carbohydrates and were absorbed on the electrode, followed by the immobilization of multiple glucose oxidase conjugated sodium alginate, which could remarkably increase the sensitivity of the biosensor with enhanced catalysis. The as-proposed ECL cytosensor was successfully applied for the detection of the MCF-7 tumor cells, whose glycans on the cell membranes are over-expressed. A low detection limit of 150   cells   mL −1 was obtained, with a wide dynamic linear range from 5.0×10 2 to 5.0×10 5   cells   mL −1 . Due to the excellent sensitivity, stability and biocompatibility, the ECL biosensor would be promising in reliable diagnostics of glycan relevant biomarkers for cancer and other diseases.

CAS / MDL: 6104-58-1 9005-38-3
研究领域: 生物传感器 · 癌症诊断 · 分析化学 · 生物化学
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Acta Biomaterialia · 2021 · IF 8.947

Near infrared light triggered ternary synergistic cancer therapy via L-arginine-loaded nanovesicles with modification of PEGylated indocyanine green

Kesi Wang,Linping Jiang,Liyan Qiu

L-arginine (L-Arg) is an important nitric oxide (NO) donor, and its exploration in NO gas therapy has received widespread attention. Application of nano-platforms that can efficiently deliver L-Arg and induce its rapid conversion to NO becomes a predominant strategy to achieve promising therapeutic effects in tumor treatment. Herein, an enhanced nano-vesicular system of ternary synergistic treatment combining NO therapy, photodynamic therapy (PDT) along with mild photothermal therapy (MPTT) was developed for cancer therapy. We integrated photosensitizer PEGylated indocyanine green (mPEG-ICG) into polyphosphazene PEP nano-vesicles through co-assembly and simultaneously encapsulated NO donor L-Arg into the vesicle center chambers to form mPEG-ICG/L-Arg co-loaded system IA-PEP. The unique nanostructure of vesicle provided considerable loading capacity for mPEG-ICG and L-Arg with 15.9% and 17.95% loading content, respectively, and efficiently prevented mPEG-ICG and L-Arg from leaking. Significantly, the reactive oxygen species (ROS) was produced by IA-PEP under 808 nm laser irradiation to perform PDT against tumors, which concurrently reacted with L-Arg to release NO and arouse gas therapy effectively. Moreover, the mild heat produced by IA-PEP could exhibit cooperative anti-tumor effect with minimal damage. As a consequence, in vivo antitumor investigation on nude mice bearing xenograft MCF-7 tumors verified the potent anti-tumor efficacy of IA-PEP under 808 nm laser irradiation with complete tumor elimination. Taken together, the IA-PEP nano-vesicle system designed in this work may provide a promising treatment paradigm for synergistic cancer treatment. Statement of significance Nitric oxide (NO) gas therapy has drawn widespread attention due to its “green” treatment paradigm with negligible side effects. L-arginine (L-Arg) is an important NO donor. However, how to efficiently deliver L-Arg and induce NO generation remains a big challenge since L-Arg is a water-soluble small molecule . Herein, we developed a nano-vesicle system IA-PEP to integrate photosensitizer PEGylated indocyanine green and L-Arg with high loading content and to produce a ternary synergistic treatment combining NO therapy, photodynamic therapy (PDT) along with mild-temperature photothermal therapy (MPTT) under 808 nm laser irradiation. The in vivo investigation on nude mice bearing xenograft MCF-7 tumors verified its potent anti-tumor efficacy with complete tumor elimination.

CAS / MDL: 5471-63-6
研究领域: 癌症治疗 · 纳米技术 · 药学 · 生物医学工程
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DRUG DELIVERY · 2022 · IF 6.819

Construction of iron-mineralized black phosphorene nanosheet to combinate chemodynamic therapy and photothermal therapy

Zhaoqing Shi,Jing Tang,Chuchu Lin,Ting Chen,Fan Zhang,Yuxing Huang,Ping Luan,Zhuo Xin,Qianqian Li,Lin Mei

Chemodynamic therapy (CDT) by triggering Fenton reaction or Fenton-like reaction to generate hazardous hydroxyl radical (•OH), is a promising strategy to selectively inhibit tumors with higher H2O2 levels and relatively acidic microenvironment. Current Fe-based Fenton nanocatalysts mostly depend on slowly releasing iron ions from Fe or Fe oxide-based nanoparticles, which leads to a limited rate of Fenton reaction. Herein, we employed black phosphorene nanosheets (BPNS), a biocompatible and biodegradable photothermal material, to develop iron-mineralized black phosphorene nanosheet (BPFe) by in situ deposition method for chemodynamic and photothermal combination cancer therapy. This study demonstrated that the BPFe could selectively increase cytotoxic ·OH in tumor cells whereas having no influence on normal cells. The IC50 of BPFe for tested tumor cells was about 3–6 μg/mL, which was at least one order of magnitude lower than previous Fe-based Fenton nanocatalysts. The low H2O2 level in normal mammalian cells guaranteed the rare cytotoxicity of BPFe. Moreover, the combination of photothermal therapy (PTT) with CDT based on BPFe was proved to kill tumors more potently with spatiotemporal accuracy, which exhibited excellent anti-tumor effects in xenografted MCF-7 tumor mice models.

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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ACS Applied Bio Materials · 2020 · IF 0

Upconversion Nanoparticle-Based Organosilica–Micellar Hybrid Nanoplatforms for Redox-Responsive Chemotherapy and NIR-Mediated Photodynamic Therapy

Zhenyang Wei,Xiaohang Liu,Dechao Niu,Limei Qin,Yongsheng Li

Upconversion nanoparticles (UCNPs) can convert near-infrared light (NIR, 980 or 808 nm) to ultraviolet (UV) or visible light, which can be widely used to improve tissue penetration depth in photodynamic therapy (PDT). Herein, we develop a kind of UCNP-based organosilica–micellar hybrid nanoplatform for redox-responsive chemotherapy and NIR-mediated PDT. The nanoplatform was constructed by the self-assembly of block copolymers polystyrene-b-poly (acrylic acid) and oil-soluble UCNPs in the oil/water system and the subsequent organosilica coating with 3-mercaptopropyltrimethoxysilane molecules. To endow the nanosystem with more stability in biological media, polyethylene glycol molecules were further modified via the Michael addition reaction. As a promising nanocarrier, chlorin e6 (Ce6) and doxorubicin (DOX) molecules were loaded into the hydrophobic core and the disulfide-doped organosilica shell, respectively. With endocytosis by SMMC-7721 tumor cells, the Ce6 and DOX coloaded nanosystem was activated by UCNPs through luminescence resonance energy transfer under the irradiation of 808 nm laser, thus generating cytotoxic 1O2 for NIR-mediated PDT. Meanwhile, DOX was selectively released because of the redox-responsive biodegradation of the disulfide-doped organosilica shell in the glutathione over-expressed SMMC-7721 tumor cells. Based on these, the chemotherapy/PDT combination toxic feature of the multifunctional nanosystem was further demonstrated in the DOX-resistant MCF-7 tumor cells. On the other hand, the Ce6 and DOX coloaded nanosystem exhibited negligible toxicity to the normal 3T3 cell because of the protective effects of organosilica coating. We envision that the resultant hybrid nanoplatform provides us a promising nanocarrier for the combination therapy of redox-responsive safe chemotherapy and efficient NIR-mediated PDT.

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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BIOMATERIALS · 2021 · IF 12.479

Hierarchical responsive micelle facilitates intratumoral penetration by acid-activated positive charge surface and size contraction

Mengcheng Ma,Yafang Chen,Mingda Zhao,Junhui Sui,Zhihao Guo,Yuedi Yang,Zhiyi Xu,Yong Sun,Yujiang Fan,Xingdong Zhang

Integrating these features of acid-activated positively charged surface and size contraction into single nanoparticle would be an effective strategy for enhancing cellular uptake, intratumoral penetration and accumulation. Here, hierarchical responsive micelle (HVDMs) was developed via RAFT reaction as multifunctional polymer-drug conjugate for maximizing penetration and therapeutic effect against MCF-7 tumor by combining positively charged surface with size contraction: surface zeta-potential reversal (−2 to +12 mV) by protonation of PHEME and size contraction (~81–~41 nm) by simultaneous hydrophobic/hydrophilic conversion (pH ≈ 6.7); the disintegration of hydrazone bond between hydrophobic PVB and DOX triggered drug release (pH ≈ 5.0). The in vitro structural stabilization, cellular uptake and anti-proliferative efficiency were significantly higher than other control groups (CVDMs and HSDMs) at pH 6.7. The markedly increased penetration depth, cellular internalization and anti-tumor efficiency were confirmed in 3D MCSs spheroids at pH 6.7, and the ex vivo DOX fluorescence images further verified obvious penetration and accumulation in internal region of solid tumor. The antitumor effect in vivo demonstrated that HVDMs accelerated tumor atrophy, induced intratumoral cells apoptosis and alleviated system toxicity.

研究领域: 纳米技术 · 癌症治疗 · 药学科学 · 材料科学
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