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NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

ABSTRACT: The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu_2-xSe nanoparticles (NPs) and DSF (DSF/Cu_2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu_2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu_2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu_2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu_2-xSe, forming Cu_2-xSe-ET complexes without the need for copper ion release. Additionally, Cu_2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu_2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.

SUBMITTER: Pan YJ

PROVIDER: S-EPMC10701282 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

Pan Yu-Jing YJ Zhang Yang Y Chen Biao-Qi BQ Zhao Yi Y Wang Jin-Yang JY Li Chang-Yong CY Zhang Da-Gui DG Kankala Ranjith Kumar RK Wang Shi-Bin SB Liu Gang G Chen Ai-Zheng AZ

Bioactive materials 20231124

The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu<sub>2-x</sub>Se nanoparticles (NPs) and DSF (DSF/Cu<sub>2-x</sub>Se@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor ...[more]

PMID: 38076647

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Project description:BackgroundReactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy.MethodsIndocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model.ResultsCompared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed.ConclusionsLipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy.

Dataset Information

NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

Publications

NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy.

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