PSMA ligand conjugated PCL-PEG polymeric micelles targeted to prostate cancer cells.
In this content, a small molecular ligand of prostate specific membrane antigen (SMLP) conjugated poly (caprolactone) (PCL)-b-poly (ethylene glycol) (PEG) copolymers with different block lengths were synthesized to construct a satisfactory drug delivery system. Four different docetaxel-loaded polymeric micelles (DTX-PMs) were prepared by dialysis with particle sizes less than 60 nm as characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Optimization of the prepared micelles was conducted based on short-term stability and drug-loading content. The results showed that optimized systems were able to remain stable over 7 days. Compared with Taxotere, DTX-PMs with the same ratio of hydrophilic/hydrophobic chain length displayed similar sustained release behaviors. The cytotoxicity of the optimized targeted DTX-PCL12K-PEG5K-SMLP micelles (DTX-PMs2) and non-targeted DTX-PCL12K-mPEG5K micelles (DTX-PMs1) were evaluated by MTT assays using prostate specific membrane antigen (PSMA) positive prostate adenocarcinoma cells (LNCaP). The results showed that the targeted micelles had a much lower IC50 than their non-targeted counterparts (48 h: 0.87 ± 0.27 vs 13.48 ± 1.03 µg/ml; 72 h: 0.02 ± 0.008 vs 1.35 ± 0.54 µg/ml). In vitro cellular uptake of PMs2 showed 5-fold higher fluorescence intensity than that of PMs1 after 4 h incubation. According to these results, the novel nano-sized drug delivery system based on DTX-PCL-PEG-SMLP offers great promise for the treatment of prostatic cancer.
Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, People's Republic of China.
Jian
J
Jin
Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, People's Republic of China.
Bowen
B
Sui
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Jingxin
J
Gou
Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, People's Republic of China.
Jingshuo
J
Liu
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Xing
X
Tang
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Hui
H
Xu
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
Yu
Y
Zhang
Department of Pharmaceutics, College of Pharmacy Sciences, Jilin University, Changchun, People's Republic of China.
Xiangqun
X
Jin
D000954:Antigens, Surface / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D043425:Glutamate Carboxypeptidase II / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008823:Micelles; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000954:Antigens, Surface; D008823:Micelles; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II