Preparation Of Photo-and Temperature-Responsive Nano-drug Delivery For Controlled Release

Stimuli responsive nanoparticles are attracting more and more attentions becauseof their potential for controlled drug delivery applications. There are two kinds ofstimuli responsive nanosystems classified according to the type of the stimuli: one isresponsive to the internal stimuli, which are often biologic properties of disease area,such as pH, temperature, redox potential, etc; and the other one is responsive to externalstimulus, such as light, ultrasound, electromagnetic field, etc. Among the various stimuli,light is a typical external stimulus and has some superior characters, for example, lightcan be easily controlled and regulated by external apparatuses, which will offers thetemporal and spatial selectivity; and light can induce various photochemical reactionswhich make it easy to exploit diversiform photosensitive materials. However, most ofphotochemical reactions are induced by ultraviolet (UV) or visible light, whose lowtissue penetration and harmful effects to normal tissue and health cells limit theirapplications as triggers of drug release.To enhance the virtues while minimize the drawbacks of the light as a trigger, twostrategies are able to be adopted. One is to alter the stimulus source. Near-infrared (NIR)light has deeper penetration into tissue and is less detrimental to healthy cells comparingto UV and visible light. However, as mentioned above, most of photochemical reactionsrequire high-energy ultraviolet (UV) or visible light. Recently, upconvertingnanoparticles (UCNPs) has emerged as a powerful tools to convert NIR light tohigher-energy photons in the UV, visible, and NIR regions. Zhao et al combineupconverting nanoparticles (UCNPs) with micelles containing photolabile4,5-dimethoxy-2-nitrobenzyl methacrylate residues, and then, by near-infrared laserirradiation, the micelles were successfully disassembled and released the payloads. Theresult indicated NIR light might be used to instead the UV light in photo-induced drugrelease.The other one is to improve the sensitivity of the nanoparticles, which may berealized by engineering light responsiveness into internal stimuli responsive materials.Internal stimuli are biologic properties of disease areas, which are relatively steady.Therefore, there is no need to worry about the intensities and durabilities of them. Wheninternal stimuli responsive materials combine with a small amount of photosensitivemoieties, the effect of photoreaction may be amplified by the internal stimuli[]. Liu et al developed thermo-and light-responsive copolymers by copolymerization ofN-isopropylacrylamide (NIPAM) and nitrobenzyl acrylate (NBA). The PNIPAM is atypical thermo-sensitive polymers, which is soluble in water below its lower criticaltemperature (LCST) at about32oC and insoluble above it. When a small amount ofNBA monomers were polymerized into PNIPAM randomly, the LCST of the copolymerdecreased below room temperature because the hydrophobic nature of the residuals ofNBA. By irradiating the copolymer with UV light at365nm, the hydrophobic part fromNBA left and the residual hydrophilic carboxyl groups increased the LCST of thecopolymer above the temperature of humman body.In this work, we synthesized PEO-b-P(NIPAM-co-NBA) diblock copolymers asthe thermo-and light-responsive materials by reversible addition fragment chaintransfer (RAFT) polymerization, where PEO represent poly(ethylene oxide), and NaYF4Tm3+Yb3+UCNPs as frequency changers of photons to combine the two strategiestogether. When UCNPs were encapsuled in the self-assemblies of thePEO-b-P(NIPAM-co-NBA), the hybrid nanoparticles would convert NIR to UV light tomake the hydrophobic residuals of NBA fall off and change the LCST of the copolymerto release the payloads.