Abstract
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 step-by-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.
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