Dataset Information

Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing.

ABSTRACT:

Background

Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive.

Results

In this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug-drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy.

Conclusion

A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system.

SUBMITTER: Ao M

PROVIDER: S-EPMC8557616 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing.

Ao Mingtao M Yu Fei F Li Yixiang Y Zhong Mengya M Tang Yonghe Y Yang Hua H Wu Xiaojing X Zhuang Yifan Y Wang Huiyun H Sun Xiaolian X Hong Xuehui X Chen Xiao Dong XD

Journal of nanobiotechnology 20211030 1

<h4>Background</h4>Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive.<h4>Results</h4>In this study, we conjugated camptothecin (C ...[more]

PMID: 34717646

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Project description:BackgroundNanomedicine has emerged as a promising strategy for cancer treatment. The most representative nanomedicine used in clinic is PEGylated liposomal doxorubicin DOXIL®, which is first FDA-approved nanomedicine. However, several shortcomings, such as low drug loading capacity, low tumor targeting, difficulty in mass production and potential toxicity of carrier materials, have hindered the successful clinical translation of nanomedicines. In this study, we report a preclinical development process of the carrier-free prodrug nanoparticles designed as an alternative formulation to overcome limitations of conventional nanomedicines in the terms of technical- and industrial-aspects.ResultsThe carrier-free prodrug nanoparticles (F68-FDOX) are prepared by self-assembly of cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates without any additional carrier materials, and further stabilized with Pluronic F68, resulting in high drug loading (> 50%). The precise and concise structure allow mass production with easily controllable quality control (QC), and its lyophilized powder form has a great long-term storage stability at different temperatures (- 4, 37 and 60 °C). With high cathepsin B-specificity, F68-FDOX induce a potent cytotoxicity preferentially in cancer cells, whereas their cytotoxicity is greatly minimized in normal cells with innately low cathepsin B expression. In tumor models, F68-FDOX efficiently accumulates within tumor tissues owing to enhanced permeability and retention (EPR) effect and subsequently release toxic DOX molecules by cathepsin B-specific cleavage mechanism, showing a broad therapeutic spectrum with significant antitumor activity in three types of colon, breast and pancreatic cancers. Finally, the safety of F68-FDOX treatment is investigated after single-/multi-dosage into mice, showing greatly minimized DOX-related toxicity, compared to free DOX in normal mice.ConclusionsCollectively, these results provide potential preclinical development process of an alternative approach, new formulation of carrier-free prodrug nanoparticles, for clinical translation of nanomedicines.

Dataset Information

Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing.

Background

Results

Conclusion

Publications

Carrier-free nanoparticles of camptothecin prodrug for chemo-photothermal therapy: the making, in vitro and in vivo testing.

Similar Datasets

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