Purpose: Efficient intracellular delivery of a therapeutic compound is an important feature of smart drug delivery systems (SDDS). Modification of a carrier structure with a cell-penetrating ligand, ie, cholesterol moiety, is a strategy to improve cellular uptake. Cholesterol end-capped poly(-isopropylacrylamide)s offer a promising foundation for the design of efficient thermoresponsive drug delivery systems.
Methods: A series of cholesterol end-capped poly(-isopropylacrylamide)s (PNIPAAm) with number-average molar masses ranging from 3200 to 11000 g·mol were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization from original xanthate-functionalized cholesterol and self-assembled into micelles. The physicochemical characteristics and cytotoxicity of cholesterol end-capped poly(-isopropylacrylamide)s have been thoroughly investigated.
Results: Phase transition temperature dependence on the molecular weight and hydrophilic/hydrophobic ratio in the polymers were observed in water. Biological test results showed that the obtained materials, both in disordered and micellar form, are non-hemolytic, highly compatible with fibroblasts, and toxic to glioblastoma cells. It was found that the polymer termini dictates the mode of action of the system.
Conclusion: The cholesteryl moiety acts as a cell-penetrating agent, which enables disruption of the plasma membrane and in effect leads to the restriction of the tumor growth. Cholesterol end-capped PNIPAAm showing in vitro anticancer efficacy can be developed not only as drug carriers but also as components of combined/synergistic therapy.
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| http://dx.doi.org/10.2147/IJN.S262582 | DOI Listing |
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