Letter pubs.acs.org/journal/abseba
Upper Critical Solution Temperature Polymer, Photothermal Agent, and Erythrocyte Membrane Coating: An Unexplored Recipe for Making Drug Carriers with Spatiotemporally Controlled Cargo Release Liwei Hui,†,§ Shuai Qin,†,§ and Lihua Yang*,†,§ †
CAS Key Laboratory of Soft Matter Chemistry and §School of Chemistry and Materials Science, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui 230026 China S Supporting Information *
ABSTRACT: “On-demand” drug release within target site is critical for targeted drug delivery systems. We herein integrate the advantages of upper critical solution temperature (UCST) polymers, photothermal agent, and red blood cell (RBC) membrane coating into a single drug delivery nanosystem and, for the first time, achieve remotely controlled UCST polymer-based drug delivery system that undergoes “on-demand” drug release within specified zone. When in laser-off state, the resulting nanosystem demonstrates significantly diminished drug self-leakage, owing to shielding by the RBC membrane coating. Upon laser irradiation, this system undergoes responsive drug release, likely because of particle swelling due to its UCST polymer component’s hydrophobic-to-hydrophilic transition triggered by the rapid localized heating generated by its preloaded photothermal agent via photothermal effects. As a result, this drug delivery system exhibits spatiotemporally controlled cytotoxicity to cultured cells, efficiently eradicating irradiated cancerous cells without appreciably impacting nonirradiated ones, those ∼0.7 cm away from the irradiation zone. This work may open an avenue to thermosensitive drug delivery systems potentially “ideal” for intravenous administration and inspire future efforts on biomedical applications of UCST polymers. KEYWORDS: drug delivery, stimuli responsive, photothermal, polymer, surface engineering “On-demand” drug release within target diseased sites is crucial for targeted drug delivery, a novel strategy that may revolutionize cancer treatment.1−5 To this end, researchers have developed diverse stimuli-sensitive systems that undergo controlled drug release at the target sites in response to specific stimuli,4 which can be internal and intrinsic to the target sites (e.g., acidic pH,6 enhanced glutathione concentration,7 and matrix metalloproteinases overexpressed by tumor cells8) or external and artificially applied (e.g., heat,9 magnetic field,10 light,11 or voltage12). Thermosensitive drug delivery systems, in particular, have attracted intensive research attention, because temperature change is facile and safe to acquire.13,14 To date, thermoresponsive drug delivery systems reported in literature are usually constructed based on the lower critical solution temperature (LCST) polymers, for example, poly(Nisopropylacrylamide)15,16 and random copolymers of 2-(2methoxyethoxy)ethyl methacrylate (MEO2MA) and oligo(ethylene glycol) methacrylate (OEGMA).17 In contrast to the LCST polymers, the upper critical solution temperature (UCST) polymers are largely neglected until very recently.18 Upon heating, a UCST polymer transits from a hydrophobic state to a hydrophilic state, a physical transition distinct from the hydrophilic-to-hydrophobic transition by a LCST polymer. As a result, UCST polymer-based matrixes undergo heating© XXXX American Chemical Society
triggered swelling or even dissociation19,20 which may promote the outward diffusion of preloaded drug, whereas the LCST polymer-based counterparts undergo heat-stimulated shrinkage and consequently extrude drug along with water.21 Clearly, UCST polymers may be an alternative class of drug carrierforming materials probably even superior to LCST polymers. Indeed, the pioneer UCST polymer-based drug delivery system reported to date demonstrates rapid and complete drug release at 43 °C and leads to cumulative drug release of >70% within 24 h,18 significantly higher than the
