Cell Membrane Capsules for Encapsulation of Chemotherapeutic and Cancer Cell Targeting in Vivo.
Systemic administration of chemotherapeutic agents can cause indiscriminate drug distribution and severe toxicity. Until now, encapsulation and targeting of drugs have typically relied on synthetic vehicles, which cannot minimize the clearance by the renal system and may also increase the risk of chemical side effects. Cell membrane capsules (CMCs) provide a generic and far more natural approach to the challenges of drug encapsulation and delivery in vivo. Here aptamer AS1411, which can recognize and bind overexpressed nucleolin on a cancer cell membrane, was chemically conjugated onto CMCs. As a result, AS1411 modified CMCs showed enhanced ingestion in certain cancer cells in vitro and accumulation in mouse cancer xenografts in vivo. Chemotherapeutics and contrast agents with therapeutically significant concentrations can be packaged into CMCs by reversible permeating their plasma membranes. The systematic administration of cancer targeting CMCs loaded with doxorubicin hydrochloride can significantly inhibit tumor growth in mouse xenografts, with significantly reduced toxicity compared to free drug. These findings suggest that cancer targeting CMCs may have considerable benefits in drug delivery and cancer treatment.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310027, People's Republic of China.
Li-Hua
LH
Peng
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
Yuan-Hong
YH
Zhang
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
Li-Jie
LJ
Han
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310027, People's Republic of China.
Chen-Zhen
CZ
Zhang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310027, People's Republic of China.
Jia-He
JH
Wu
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310027, People's Republic of China.
Xia-Rong
XR
Wang
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310027, People's Republic of China.
Jian-Qing
JQ
Gao
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, People's Republic of China.
Zheng-Wei
ZW
Mao
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism; D002214:Capsules / Q000737:chemistry*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D000097796:Nucleolin
D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D002214:Capsules; D004317:Doxorubicin; D004337:Drug Carriers; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin
cancer treatment; cell membrane capsules; drug delivery; reversible permeating; targeting