Development of octreotide-conjugated polymeric prodrug of bufalin for targeted delivery to somatostatin receptor 2 overexpressing breast cancer in vitro and in vivo.
BACKGROUND
Development of polymeric prodrugs of small molecular anticancer drugs has become one of the most promising strategies to overcome the intrinsic shortcomings of small molecular anticancer drugs and improve their anticancer performance.


METHODS
In the current work, we fabricated a novel octreotide (Oct)-modified esterase-sensitive tumor-targeting polymeric prodrug of bufalin (BUF) and explored its anticancer performance against somatostatin receptor 2 overexpressing breast cancer.


RESULTS
The obtained tumor-targeting polymeric prodrug of BUF, P(oligo[ethylene glycol] monomethyl ether methacrylate [OEGMA]-co-BUF-co-Oct), showed a nanosize dimension and controlled drug release features in the presence of esterase. It was demonstrated by in vitro experiment that P(OEGMA-co-BUF-co-Oct) showed enhanced cytotoxicity, cellular uptake, and apoptosis in comparison with those of free BUF. In vivo experiment further revealed the improved accumulation of drugs in tumor tissues and enhanced anticancer performance of P(OEGMA-co-BUF-co-Oct).


CONCLUSIONS
Taken together, this study indicated that polymeric prodrug of BUF holds promising potential toward the treatment of somatostatin receptor 2 overexpressing breast cancer.
Centralab, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Tao
T
Liu
Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Tingting
T
Jia
Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Xia
X
Yuan
Centralab, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Cheng
C
Liu
Centralab, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Jian
J
Sun
Centralab, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Zhenhua
Z
Ni
Centralab, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Jian
J
Xu
Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Xuhui
X
Wang
Department of Pharmacy, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.
Yi
Y
Yuan
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002018:Bufanolides / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D057446:Hydrodynamics; D061986:MCF-7 Cells; D008689:Methacrylates / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008823:Micelles; D015282:Octreotide / Q000494:pharmacology / Q000627:therapeutic use*; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D014018:Tissue Distribution / Q000187:drug effects
D000970:Antineoplastic Agents; D002018:Bufanolides; D008689:Methacrylates; D008823:Micelles; D011108:Polymers; D011355:Prodrugs; D017481:Receptors, Somatostatin; C093733:somatostatin receptor 2; D015282:Octreotide; C022777:bufalin
controlled release; esterase responsive; tumor targeting