Temperature-Induced Intracellular Uptake of Thermoresponsive Polymeric Micelles

Citations Over TimeTop 10% of 2009 papers

Abstract

Well-defined diblock copolymers comprising thermoresponsive segments of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) (P(IPAAm-co-DMAAm)) and hydrophobic segments of poly(d,l-lactide) were synthesized by combination of RAFT and ring-opening polymerization methods. Terminal conversion of thermoresponsive segments was achieved through reactions of maleimide or its Oregon Green 488 (OG) derivative with thiol groups exposed by cleavage of polymer terminal dithiobenzoate groups. Thermoresponsive micelles obtained from these polymers were approximately 25 nm when below the lower critical solution temperature (LCST) of 40 degrees C, and their sizes increased to an average of approximately 600 nm above the LCST due to aggregation of the micelles. Interestingly, the OG-labeled thermoresponsive micelles showed thermally regulated internalization to cultured endothelial cells, unlike linear thermoresponsive P(IPAAm-co-DMAAm) chains. While intracellular uptake of P(IPAAm-co-DMAAm) was extremely low at temperatures both below and above the micellar LCST, the thermoresponsive micelles showed time-dependent intracellular uptake above the LCST without exhibiting cytotoxicity. These results indicate that the new thermoresponsive micelle system may be a greatly promising intracellular drug delivery tool.

Related Papers

• → Preparation and Characterization of Thermoresponsive Poly(N-Isopropylacrylamide) for Cell Culture Applications(2020)87 cited
• → Poly(N‐isopropylacrylamide)‐Based Polymers: Recent Overview for the Development of Temperature‐Responsive Drug Delivery and Biomedical Applications(2023)71 cited
• → Modification of Thermoresponsive Poly(<i>N</i>-Isopropylacrylamide) End-Group with Hydrophilic and/or Hydrophobic Compounds Tuned the LCST(2022)1 cited
• → Nanometer-scale physically adsorbed thermoresponsive films for cell culture(2016)10 cited
• Application of Thermosensitivity Polymers Based on Poly (N-isopropylacrylamide)(2004)