Zhang Qian, Xiao Qi, Yin Honglin, Xia Chengwan, Pu Yumei, He Zhifeng, Hu Qingang, Wang Jianquan, Wang Yuxin
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University Nanjing China
School of Medical Imaging, Bengbu Medical College Bengbu 233030 Anhui China
RSC Adv. 2020 Jul 29;10(47):28314-28323. doi: 10.1039/d0ra05630h. eCollection 2020 Jul 27.
A multimodal drug delivery system targeting the tumor microenvironment is an inspiring method for treating cancer tissues, including oral squamous cell carcinomas (OSCC). Such approaches require an efficient and safe drug carrier. Bovine milk derived exosomes are ideal because the source is adequate and have advantages of both synthetic and cell-mediated nano carriers. In the present study, we developed a pH/light sensitive drug system based on milk-exosomes for OSCC therapy. It was called exosome-doxorubicin-anthracene endoperoxide derivative (Exo@Dox-EPT1, NPs). Milk-exosomes were conjugated to doxorubicin (Dox) by a pH-cleavable bond, which can rapture under an acidic microenvironment. Besides, endoperoxides and chlorin e6 (Ce6) were also loaded and the endoperoxides undergo thermal cycloreversion and release singlet oxygen to kill cancer cells. We have also investigated the body distribution, antitumor effects, and biocompatibility of the nanoparticles. The new milk-exosome-based drug delivery system showed controlled drug-release, biocompatibility and, proved to be effective in treating OSCC.
一种靶向肿瘤微环境的多模态药物递送系统是治疗包括口腔鳞状细胞癌（OSCC）在内的癌组织的一种鼓舞人心的方法。此类方法需要一种高效且安全的药物载体。源自牛乳的外泌体是理想之选，因为其来源充足，兼具合成纳米载体和细胞介导纳米载体的优势。在本研究中，我们开发了一种基于乳外泌体的pH/光敏感药物系统用于OSCC治疗。它被称为外泌体-阿霉素-蒽内过氧化物衍生物（Exo@Dox-EPT1，纳米颗粒）。乳外泌体通过一种可在酸性微环境下断裂的pH可裂解键与阿霉素（Dox）偶联。此外，还负载了内过氧化物和二氢卟吩e6（Ce6），内过氧化物发生热环反转并释放单线态氧以杀死癌细胞。我们还研究了纳米颗粒的体内分布、抗肿瘤效果和生物相容性。这种基于乳外泌体的新型药物递送系统显示出可控的药物释放和生物相容性，并被证明对治疗OSCC有效。
