Engineered Cell‐Derived Microparticles Bi2Se3/DOX@MPs for Imaging Guided Synergistic Photothermal/Low‐Dose Chemotherapy of Cancer

• Published in: Advanced science Vol. 7; no. 3; pp. 1901293 - n/a
• Main Authors: Wang, Dongdong, Yao, Yuzhu, He, Junkai, Zhong, Xiaoyan, Li, Basen, Rao, Shiyu, Yu, Haiting, He, Shuaicheng, Feng, Xiaoyu, Xu, Tuo, Yang, Bin, Yong, Tuying, Gan, Lu, Hu, Jun, Yang, Xiangliang
• Format: Journal Article
• Language: English
• Published: Hoboken John Wiley and Sons Inc 01.02.2020; Wiley
• Subjects: cell‐derived microparticles; dual‐modal imaging; electroporation; membrane fusion; synergistic therapy
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.201901293

Cell‐derived microparticles, which are recognized as nanosized phospholipid bilayer membrane vesicles, have exhibited great potential to serve as drug delivery systems in cancer therapy. However, for the purpose of comprehensive therapy, microparticles decorated with multiple therapeutic components are needed, but effective engineering strategies are limited and still remain enormous challenges. Herein, Bi2Se3 nanodots and doxorubicin hydrochloride (DOX) co‐embedded tumor cell‐derived microparticles (Bi2Se3/DOX@MPs) are successfully constructed through ultraviolet light irradiation‐induced budding of parent cells which are preloaded with Bi2Se3 nanodots and DOX via electroporation. The multifunctional microparticles are obtained with high controllability and drug‐loading capacity without unfavorable membrane surface destruction, maintaining their excellent intrinsic biological behaviors. Through membrane fusion cellular internalization, Bi2Se3/DOX@MPs show enhanced cellular internalization and deepened tumor penetration, resulting in extreme cell damage in vitro without considering endosomal escape. Because of their distinguished photothermal performance and tumor homing target capability, Bi2Se3/DOX@MPs exhibit admirable dual‐modal imaging capacity and outstanding tumor suppression effect. Under 808 nm laser irradiation, intravenous injection of Bi2Se3/DOX@MPs into H22 tumor‐bearing mice results in remarkably synergistic antitumor efficacy by combining photothermal therapy with low‐dose chemotherapy in vivo. Furthermore, the negligible hemolytic activity, considerable metabolizability, and low systemic toxicity of Bi2Se3/DOX@MPs imply their distinguished biocompatibility and great potential for tumor theranostics. Multifunctional cell‐derived microparticles Bi2Se3/DOX@MPs are successfully fabricated via electroporation with high efficiency and controllability for computed tomography and photoacoustic imaging guided synergistic photothermal/low‐dose chemotherapy. The obtained Bi2Se3/DOX@MPs show enhanced intracellular uptake through membrane fusion mediated cellular internalization, which not only strengthens their cytotoxicity by avoiding endosomal trapping, but also deepens their penetration in H22 3D tumor spheroids.