Bacterial protoplast-derived nanovesicles for tumor targeted delivery of chemotherapeutics.
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.
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Oh Youn
OY
Kim
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Nhung Thi Hong
NT
Dinh
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Hyun Taek
HT
Park
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Seng Jin
SJ
Choi
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Kahye
K
Hong
Department of Life Sciences, Pohang University of Science and Technology, Pohang 37673, Republic of Korea. Electronic address: ysgho@postech.ac.kr.
Yong Song
YS
Gho
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011523:Protoplasts / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D004337:Drug Carriers; D053769:Nanocapsules; D066246:ErbB Receptors
Bacterial protoplast; Chemotherapy; Extracellular vesicles; Nanovesicles; Targeted delivery system