Glyconanoparticles for targeted tumor therapy of platinum anticancer drug

An important requirement to decrease the side effects of chemotherapy drugs is to develop nanocarriers with precise biological functions. In this work, a set of glyconanoparticles was prepared via self-assembly of amphiphilic glycoblock copolymers for the targeted delivery of a hydrophobic chemotherapy drug. Well-defined glycoblock copolymers that consist of 1,1-di-tert-butyl 3-(2-(metyloyloxy)ethyl)-butane-1,1,3-tricarboxylate (MAETC) together with three different protected-sugar moieties (?-d-glucopyranoside, ?-d-mannopyranoside, and ?-l-fucopyranoside) were synthesized by using reversible addition-fragmentation chain-transfer polymerization. Copolymers were deprotected and conjugated with the cis-dichlorodiammineplatinum(II) (cis-Pt) anticancer drug. Dynamic light scattering and transmission electron microscopy measurements revealed that cis-Pt-conjugated glyconanoparticles were sufficiently stable under physiological conditions and had diameters of approximately 100 nm with considerably narrow size distributions. They were intracellularly taken up by the breast cancer (MCF-7 and MDA-MB-231), prostate cancer (PC3), renal cancer (769-P), and Chinese hamster ovary cell lines. The PC3 and 769-P cell lines showed a high preference for the glycosylated nanoparticles. Glycoblock copolymers were found nontoxic but showed high cytotoxicity and increased efficacy after conjugation with the cis-Pt anticancer drug. Moreover, in vitro cytotoxicity assays in cancer cell lines demonstrate that cis-Pt-loaded glycopolymer-based nanoparticles have higher cytotoxicity than free cis-Pt. Overall, our results suggest that glyconanoparticles have a great potential to be used as an effective cis-Pt drug carrier for targeted cancer therapy.