Bioinspired Nano-Prodrug with Enhanced Tumor Targeting and Increased Therapeutic Efficiency.
Nanotechnology-based drug delivery has a great potential to revolutionize cancer treatment by enhancing anticancer drug efficacy and reducing drug toxicity. Here, a bioinspired nano-prodrug (BiNp) assembled by an antineoplastic peptidic derivative (FA-KLA-Hy-DOX), a folate acid (FA)-incorporated proapoptotic peptide (KLAKLAK)(2) (KLA) to doxorubicin (DOX) via an acid-labile hydrozone bond (Hy) is constructed. The hydrophobic antineoplastic agent DOX is efficiently shielded in the core of nano-prodrug. With FA targeting moieties on the surface, the obtained BiNp shows significant tumor-targeting ability and enhances the specific uptake of cancer cells. Upon the trigger by the intracellular acidic microenvironment of endosomes, the antineoplastic agent DOX is released on-demand and promotes the apoptosis of cancer cells. Simultaneously, the liberated FA-KLA can induce the dysfunction of mitochondria and evoke mitochondria-dependent apoptosis. In vitro and in vivo results show that the nano-prodrug BiNp with integrated programmed functions exhibits remarkable inhibition of tumor and achieves a maximized therapeutic efficiency with a minimized side effect.
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Wei-Hai
WH
Chen
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Qi
Q
Lei
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Cai-Xia
CX
Yang
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Hui-Zhen
HZ
Jia
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Guo-Feng
GF
Luo
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Xiao-Yong
XY
Wang
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Gang
G
Liu
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.
Si-Xue
SX
Cheng
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, P. R. China.|The Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China.|Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, Wuhan, 430068, China.
Xian-Zheng
XZ
Zhang
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D040761:Biomimetic Materials / Q000008:administration & dosage / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004357:Drug Synergism; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis
D000903:Antibiotics, Antineoplastic; D053769:Nanocapsules; D011355:Prodrugs; D004317:Doxorubicin; D005492:Folic Acid
apoptosis; nano-prodrug; subcellular therapy; tumor targeting, drug delivery