Although nanomedicine has offered exciting alternatives to improve cancer treatments, patient responses are below expected due to a complex series of protective barriers inside the human body. In this context, incorporation of multiple functionalities into a single nanoparticle has been proposed to address these obstacles. In this study, we developed multifunctional doxorubicin (DOX)-loaded nanocarriers based on dendrimer-b-poly(N-isopropylacrylamide) (PNIPAM) block copolymers. First, second, and third generation of Janus-like polyamide dendrimers containing only one azide group were synthesized by stepwise reactions until final functionalization with a glycol spacer and folate targeting groups. PNIPAM homopolymers were prepared using the reversible addition-fragmentation chain-transfer (RAFT) polymerization followed by end-functionalization with a cyclooctyne derivative. The block copolymers were constructed by the grafting to approach via strain-promoted alkyne-azide cycloaddition (SPAAC) reactions. Self-assembly investigation revealed the formation of nano-sized spherical micelles with low polydispersities. The micelles showed thermo- and pH-responsive behaviors, and negative zeta potential. The DOX-loaded micelles possess high drug loading contents (up to 46.4%) and high entrapment efficiencies (up to 86.5%). In vitro DOX release experiments indicate controlled release behavior, which was suppressed at pH 7.2 and accelerated at pH 5.0. Moreover, electrochemistry impedance spectroscopy (EIS) revealed that all conjugates are able to bind to gold surfaces via trithiocarbonate-gold interactions to form self-assembled monolayers. Hence, these dendrimer-PNIPAM conjugates are promising candidates as drug delivery and sensing systems with specific targeting of Frα-positive tumors.

Synthesis and self-assembly of dendrimer-b-poly(N-isopropylacrylamide) block copolymers containing folates for applications in biosensors and drug delivery systems

2019 Fall National Meeting

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