Glyconanoparticles for targeted tumor therapy of platinum anticancer drug
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CitationDağ, A., Omurtag Özgen, P. S. ve Atasoy, S. (2019). Glyconanoparticles for targeted tumor therapy of platinum anticancer drug. Biomacromolecules, 20(8), 2962-2972. http://dx.doi.org/10.1080/19186444.2019.1616508
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 (β-d-glucopyranoside, β-d-mannopyranoside, and β-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.