Cyclic RGD peptide-modified liposomal drug delivery system for targeted oral apatinib administration: enhanced cellular uptake and improved therapeutic effects.
Apatinib is an oral tyrosine kinase inhibitor, which selectively targets vascular endothelial growth factor receptor 2 and has the potential to treat many tumors therapeutically. Cyclic arginylglycylaspartic acid (cRGD)- and polyethylene glycol (PEG)-modified liposomes (cRGD-Lipo-PEG) were constructed to act as a targeted delivery system for the delivery of apatinib to the human colonic cancer cell line, HCT116. These cRGD-modified liposomes specifically recognized integrin αvβ3and exhibited greater uptake efficiency with respect to delivering liposomes into HCT116 cells when compared to nontargeted liposomes (Lipo-PEG), as well as greater death of tumor cells and apoptosis. The mechanism by which cRGD-Lipo-PEG targets cells was elucidated further with competition assays. To determine the anticancer efficacy in vivo, nude mice were implanted with HCT116 xenografts and treated with apatinib-loaded liposomes or free apatinib intravenously or via intragastric administration. The active and passive targeting of cRGD-Lipo-PEG led to significant tumor treatment targeting ability, better inhibition of tumor growth, and less toxicity when compared with treatments using uncombined apatinib. The results presented strongly support the case for cRGD-Lipo-PEG representing a targeted delivery system for apatinib in the treatment of colonic cancer.
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Zhiwang
Z
Song
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Yun
Y
Lin
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Xia
X
Zhang
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Chan
C
Feng
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Yonglin
Y
Lu
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Yong
Y
Gao
Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Chunyan
C
Dong
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D045325:HCT116 Cells; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D055672:Static Electricity; D014018:Tissue Distribution / Q000187:drug effects
D039302:Integrin alphaVbeta3; D008081:Liposomes; D010456:Peptides, Cyclic; D011725:Pyridines; C507169:cyclic arginine-glycine-aspartic acid peptide; C553458:apatinib
apatinib; cRGD; colorectal cancer; integrin αvβ3; targeted oral therapy