Nanoscopic vehicles that stably encapsulate drug molecules and release them in response to a specific trigger are of great interest due to implications in therapeutic applications, especially for cancer therapy. For this purpose, we have synthesized highly stable polymeric nanogels, in which the kinetics of guest molecule release can be fine-tuned by control over cross-linking density. The polymer nanogel precursor is based on a random copolymer that contains oligoethyleneglycol (OEG) and pyridyldisulfide (PDS) units as side-chain functionalities. By introducing variations into the precursor polymer, such as molecular weight and the relative percentages of hydrophilic OEG units and hydrophobic PDS functionalities, we have achieved significant control over nanogel size. We show that the noncovalently encapsulated guest molecules can be released in response to a redox trigger, glutathione (GSH). Stability of dye encapsulation inside the nanogels and tunability in the release of guest molecules have been demonstrated through in vitro fluorescence resonance energy transfer (FRET) experiments. We show in vitro doxorubicin delivery into breast cancer cells (MCF-7) with nanogels of different cross-linking density to demonstrate that it plays a key role in the stable encapsulation of hydrophobic drug molecules and the cell-uptake efficiencies.
A series of dodecyl-based monofunctional trithiocarbonate chain transfer agents (CTAs) were successfully synthesized, toward the reversible addition-fragmentations chain transfer (RAFT) polymerization of styrene. The CTAs were used as initiators for RAFT polymerization, in the absence of the conventional free radical initiator, at higher temperature. Polystyrene (PS) of narrow polydispersity index (PDI) is synthesized. Subsequently, poly(styrene-b-benzyl methacrylate) diblock and poly(styrene-b-benzyl methacrylate-b-2-vinyl pyridine) triblock copolymers were synthesized from the PS macro-RAFT agent by simply heating with the second and third monomer, respectively. These experiments suggest that it should be possible to control the RAFT polymerization initiated by a CTA through the adjustment of the temperature of polymerization in such manner that initiation is tailored to proceed at faster rate (at higher tem-perature) in comparison to propagation (lower temperature). For the specific CTAs studied in this work, the polymerization rate of styrene was high in the case of the reinitiating cyano (CN)-substituted group (R group) compared to the other groups studied.The results further show that 4-cyano pentanoic acid group is superior to the other R groups used for the RAFT polymerization of styrene, especially based on the polydispersity at a given conversion as well as the variation in the expected and experimental number-average-molecular weights.
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