Wenjun Chen1, Miao Guo2, Shuli Wang2. 1. a Department of Oncology , Linyi People's Hospital , Linyi , Shandong , P. R. China ; 2. b Department of Gerontology , Linyi People's Hospital , Linyi , Shandong , P. R. China.
Abstract
CONTEXT: Prostate cancer (PCa) is the second most-frequently diagnosed cancer in men. Cabazitaxel was approved for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. OBJECTIVE: In this study, bombesin (BN), a ligand reported to specifically target GRP overexpressing prostate tumor, was applied for the construction of lipid-polymer hybrid nanoparticles (LPNs), and used for the targeted delivery of cabazitaxel (CAB) to prostate cancer. METHODS: BN-polyethylene glycol-1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (BN-PEG-DSPE) was synthesized. CAB loaded, BN-PEG-DSPE contained LPNs (BN-CAB-LPNs) were prepared. Their particle size, zeta potential and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study of BN-CAB-LPNs was tested in LNCaP human prostatic cancer cell line (LNCaP cells). In vivo anti-tumor efficacy of the carriers was evaluated on mice bearing prostate cancer model. RESULTS: The optimum BN-CAB-LPNs formulations had a particle size of 184.9 nm and a 26.5 mV positive surface charge. The growth of LNCaP cells in vitro was obviously inhibited. BN-CAB-LPNs also displayed better anti-tumor activity than the other formulations in vivo. CONCLUSION: The results demonstrated that BN-CAB-LPNs can sufficiently deliver CAB to the cancer cells and enhance the anti-tumor capacity. Thus, BN-CAB-LPNs can be proved to be a superior nanomedicine which can achieve better therapeutic efficacy of prostate tumor.
CONTEXT: Prostate cancer (PCa) is the second most-frequently diagnosed cancer in men. Cabazitaxel was approved for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. OBJECTIVE: In this study, bombesin (BN), a ligand reported to specifically target GRP overexpressing prostate tumor, was applied for the construction of lipid-polymer hybrid nanoparticles (LPNs), and used for the targeted delivery of cabazitaxel (CAB) to prostate cancer. METHODS:BN-polyethylene glycol-1,2-Distearoyl-sn-glycero-3-phosphoethanolamine (BN-PEG-DSPE) was synthesized. CAB loaded, BN-PEG-DSPE contained LPNs (BN-CAB-LPNs) were prepared. Their particle size, zeta potential and drug encapsulation efficiency (EE) were evaluated. In vitro cytotoxicity study of BN-CAB-LPNs was tested in LNCaP humanprostatic cancer cell line (LNCaP cells). In vivo anti-tumor efficacy of the carriers was evaluated on mice bearing prostate cancer model. RESULTS: The optimum BN-CAB-LPNs formulations had a particle size of 184.9 nm and a 26.5 mV positive surface charge. The growth of LNCaP cells in vitro was obviously inhibited. BN-CAB-LPNs also displayed better anti-tumor activity than the other formulations in vivo. CONCLUSION: The results demonstrated that BN-CAB-LPNs can sufficiently deliver CAB to the cancer cells and enhance the anti-tumor capacity. Thus, BN-CAB-LPNs can be proved to be a superior nanomedicine which can achieve better therapeutic efficacy of prostate tumor.
Entities:
Keywords:
Bombesin; PEGylated; cabazitaxel; nano-sized drug delivery system; prostate cancer