Bacterial protoplast-derived nanovesicles for tumor targeted delivery of chemotherapeutics

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• 作者：Oh Youn Kim¹ ; Nhung Thi Hong Dinh¹ ; Hyun Taek Park ; Seng Jin Choi ; Kahye Hong ; Yong Song Gho ; ^{ysgho@postech.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Targeted delivery system ; Bacterial protoplast ; Extracellular vesicles ; Chemotherapy ; Nanovesicles
• 刊名：Biomaterials
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：113
• 期：Complete
• 页码：68-79
• 全文大小：3612 K

文摘

Increasing incidents of patients diagnosed with cancer have brought massive improvement in the delivery technologies to help patients receiving chemotherapy. However, tumor specific targeting of the chemotherapeutics still remains as a challenge mainly due to the difficulties in the conjugation and manipulation of bio-specific molecules on the surface. Herein, we genetically engineered bacterial protoplast to develop nanovesicles having no toxic outer membrane components that can specifically target and deliver chemotherapeutics to tumor tissues. The bacterial protoplast nanovesicles expressing tumor-targeting moieties on the surface were prepared by serial extrusions through nano-sized membrane filters. The nano-sized vesicular structure of protoplast nanovesicles offers passive targeting to solid tumor site and expression of tumor-targeting moiety enhance tumor-specific uptake via receptor-mediated targeting. Chemotherapeutics-loaded in the nanovesicles induce dose-dependent cytotoxicity in tumor cells in vitro. Moreover, specific trafficking of drug-loaded nanovesicles to the tumor tissue and efficient prevention of tumor growth in tumor xenografted mice are shown. Importantly, this tumor growth suppression of protoplast nanovesicles has shown to reduce the chemotherapeutics-induced adverse effects after systemic administration to mice. This study offers great potential of protoplast nanovesicles as effective and safe delivery system to optimize and contribute to the development of advanced chemotherapy.