期刊
ACTA PHARMACEUTICA SINICA B
卷 12, 期 8, 页码 3354-3366出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2022.03.010
关键词
Shape transformation; Charge reversal; Chemo-photodynamic therapy; Self-delivery; MMP-2 response; pH response; Carrier-free nanoparticles; Breast cancer
资金
- National Natural Science Foundation of China [82173762]
- 111 Project (China) [B18035]
- Key Research and Development Program of Science and Technology Department of Sichuan Province [2022JDJQ0050, 2022YFS0334]
- Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China
In this study, a dual-response shape transformation and charge reversal strategy was designed to improve the anti-tumor effect using chemo-photodynamic therapy. The tumor microenvironment-responsive nanoparticles were constructed to achieve charge reversal, size reduction, and enhanced tumor penetration, and induce tumor cell death by releasing chemotherapy drugs through the photosensitizer.
Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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