We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(...We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.展开更多
基金financially supported by the Fundamental Research Funds for the Central Universities(for M.Shen and X.Shi)the National Natural Science Foundation of China(Nos.81761148028and 21773026)the Science and Technology Commission of Shanghai Municipality(Nos.15520711400 and 17540712000)
文摘We present here the development of cholesterol(Chol)-modified dendrimer system for targeted chemotherapy of folate(FA)receptor-expressing cancer cells. In our study, poly(amidoamine)(PAMAM) dendrimers of generation 5(G5) were functionalized stepby-step with Chol, fluorescein isothiocyanate(FI), and FA via a poly(ethylene glycol)(PEG) spacer(PEG-FA), and then acetamide to shield their remaining surface amines. The synthesized G5.NHAc-Chol-FI-PEG-FA(for short, G5-CFPF) dendrimers were utilized to encapsulate 10-hydroxycamptothecin(HCP), a hydrophobic anticancer drug. We find that each G5-CFPF dendrimer can encapsulate 13.8 HCP molecules. The complexes show a slower release profiles of HCP in a pH-dependent manner than the control complexes formed using the same dendrimers without Chol under the same conditions. Thanks to the targeting role played by FA, the complexes display a specific inhibition efficacy to FA receptor-expressing cervical cancer cells. The designed Chol-modified dendrimers may be adopted as a promising carrier for application in targeted cancer therapy.
