# Automatic Detoxification Medicine Delivery by Thermo-Sensitive Poly(ethylene glycol)-Based Nanogels
); [EMAIL_ADDRESS] (J.W. ); [EMAIL_ADDRESS] (Y.Z. ); [EMAIL_ADDRESS] (T.W.) [PERSON]  
1 College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650500, China; [EMAIL_ADDRESS] (T.F. ); [EMAIL_ADDRESS] (Y.M. ); [EMAIL_ADDRESS] (J.W. ); [EMAIL_ADDRESS] (Y.Z. ); [EMAIL_ADDRESS] (T.W.) [PERSON]  
1 College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650500, China; [EMAIL_ADDRESS] (T.F. ); [EMAIL_ADDRESS] (Y.M. ); [EMAIL_ADDRESS] (J.W. ); [EMAIL_ADDRESS] (Y.Z. ); [EMAIL_ADDRESS] (T.W.) [PERSON]  
1 College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming 650500, China; [EMAIL_ADDRESS] (T.F. ); [EMAIL_ADDRESS] (Y.M. ); [EMAIL_ADDRESS] (J.W. ); zyh_12342022@163. Environmentally sensitive nanogels have been explored as drug delivery carriers for biological applications [7; 8]. Among a variety of nanogels, core-shell structure nanogels can provide an enhanced efficacy for loading a medicine with their tunable hydrophobic cores, and achieve the controlled release of a medicine through their smart shell components [9]. Recently, sensitive shell components have been thoroughly explored for drug delivery applications. Environmental stimuli include changes in pH, temperature, light, concentration of glucose and so on [10; 11; 12; 13]. Thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM)-based nanogels are one of these previous study objects [14; 15]. However, it was found that the application of these PNIPAM-based nanogels is limited because of their inherent biocompatibility problem [16]. To better adapt the biocompatibility of drug delivery systems, a new thermo-sensitive polymer containing short-side-chain oligo(ethylene glycol) units was developed [17]. It was reported that controlling the components of the oligo(ethylene glycol) side-chain units can adjust the lower critical solution temperature (LCST) of this polymer. For example, a tunable LCST was achieved with the different comonomer ratios of 2-(2-methoxyethoxy)ethyl methacrylate (MEO\({}_{2}\)MA) and oligo (ethylene glycol) methyl ether methacrylate (\(M_{\text{n}}\) = 475 g mol\({}^{-1}\), MEO\({}_{9}\)MA) [18; 19; 20]. According to [PERSON] et al., the oligo(ethylene glycol) side-chain length determined the LCST of the poly[oligo (ethylene glycol) alkyl ether methylates] [21; 22]. Recently, this nonlinear poly(ethylene glycol)-based copolymer was used to loading/release active bio(macro)molecules [23]. The core-shell structure nanogels with a tunable polymer core and thermo-responsive short oligo(ethylene glycol) side-chain shell have exhibited obvious advantages for drug loading/release and chemotherapy [24; 25]. In these core-shell structure nanogels, a hydrophobic polymer core was usually used to load hydrophobic medicines, and a hydrophilic shell with a short oligo(ethylene glycol) side-chain copolymer provided a thermo-sensitive function to effectively release the medicines [26]. We believe that the efficient loading of high-detoxification medicines and smart stimuli release can be achieved if a proper hydrophobic polymer core is combined with a thermo-sensitive nonlinear poly(ethylene glycol)-based copolymer shell. To demonstrate this concept, we report a preparation of core-shell structured nanogels with a polystyrene (PS) microsphere as the core and PEG-copolymers containing short-side-chain oligo(ethylene glycol) units as the shell to integrate the high-detoxification medicine loading yields and thermo-sensitive release. As shown in Scheme 1, the core is composed of a hydrophobic PS microsphere, which could provide a hydrophobic network structure to load detoxification medicines. The shell layer consists of a hydrophilic copolymer of 2-(2-methoxyethoxy)ethyl methacrylate (MEO\({}_{2}\)MA) and oligo(ethylene glycol) methyl ether methylates (MEO\({}_{5}\)MA), which is expected to offer a tunable thermosensitive control in the loading/release of detoxification medicines.