International Journal of Nanomedicine (Jan 2020)
Near-Infrared Laser-Triggered, Self-Immolative Smart Polymersomes for in vivo Cancer Therapy
Abstract
Qing Tang,* Ping Hu,* Haibo Peng, Ning Zhang, Qiang Zheng, Yun He School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun HeSchool of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, 55 South Daxuecheng Road, Chongqing 401331, People’s Republic of ChinaTel +86 23 6567 8450Fax +86 23 65678455Email [email protected]: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy.Methods: In our study, poly (propylene sulfide) 20-bl-poly (ethylene glycol) 12 (PPS 20-b-PEG 12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome.Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O 2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O 2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group).Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.Keywords: near infrared laser, photodynamic therapy, oxidation-responsive, polymersome, combination therapy, cancer
