Biocompatible stimuli‐responsive nanogels for controlled antitumor drug delivery

Abstract

Herein, the synthesis and potential application as cargo delivery systems of thermo-responsive poly(N-vinylcaprolactam) (PVCL)-based, pH-responsive poly(2-(diethylamino)ethyl) methacrylate (PDEAEMA)-based, and thermo-, and pH-responsive PDEAEMA/PVCL-based core-shell nanogels are reported. All the nanogels have been synthesized using different dextranmethacrylates (Dex-MAs) as macro-cross-linkers. Doxorubicin hydrochloride (DOXO), an anticancer drug, has been effectively loaded into nanogels via hydrogen-bonding interactions between AOH groups of DOXO and AOH groups of Dex-MA chains. Drugrelease profiles at various pHs, and the cytocompatibility of the DOXO-loaded nanogels have been assessed in vitro using cervi-cal cancer HeLa and breast cancer MDA-MB-231 cell lines. In all the cases, the DOXO release is controlled by Fickian diffusion and case-II transport, being the diffusional process dominant. In addition, DOXO-loaded nanogels are efficiently internalized by HeLa and MDA-MB-231 cells and DOXO is progressively released in time. Therefore, nanogels synthesized could be suitable and potentially useful as nanocarriers for antitumor drug delivery.

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…Although the LCST of PNIPAM is about 32 °C, which makes this polymer an appropriate temperature-sensitive biomaterial, the non-biodegradability of PNIPAM impedes its widespread use in clinical applications. PNIPAM-based drug carriers can be modified with different functional groups for targeted drug delivery [ 76 ], controlled release [ 77 ], imaging and tracking [ 47 ], as well as other functionalities [ 66 ]. Zhou et al investigated doxorubicin (DOX) release from a temperature-sensitive and photoluminescent hydrogel using PNIPAM and cadmium telluride quantum dots (CdTe QDs) (photoluminescent inducer) with polyacrylamide (PAA) as a crosslinker.…”

The Potential of Stimuli-Responsive Nanogels in Drug and Active Molecule Delivery for Targeted Therapy

“…This is the case of pH- and temperature-responsive NGs obtained by emulsion copolymerization of VCL with an ionizable comonomer (acrylic acid) as in the case of the preparation of acid containing PVCL-based nanogels [23,24]. More recently, the synthesis of poly(2-(diethylamino)ethyl) methacrylate (PDEAEMA)-based nanogels with dual pH and temperature sensitivities [25], as well as the synthesis of PDEAEMA/PVCL-based core-shell thermo- and pH-responsive nanogels prepared by seeded batch emulsion polymerization [26], have been reported.…”

“…On the other hand, cellular uptake studies exhibited that Dox-loaded NGs were located at endosomes or lysosomes and Dox molecules were gradually released to the cytoplasm. These NGs were proved to meet the requirements for an ideal nanocarrier in HeLa and MDA-MB-231 cell lines [26].…”

Cationic Thermoresponsive Poly(N-vinylcaprolactam) Microgels Synthesized by Emulsion Polymerization Using a Reactive Cationic Macro-RAFT Agent

“…16,17 Therefore, the synthesis of PVCL-based microgels has attracted a growing interest within the last years. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] The design of cationic thermoresponsive microgels is very attractive for various-applications. 14 Indeed, cationic polymer particles are advantageous to interact favorably with negatively charged surfaces such as for instance cell surface or cellulosic surface.…”