하이드로젤 (hydrogel)은 높은 친수성을 갖지만 물에는 불용성인 3차원 고분자 네트워크의 한 종류로서 고분자 사슬이 물리적 또는 화학적인 가교로 인해서 합성할 수 있습니다. 또한 크기별로 nanogel (20-200 nm), microgel (300-1000 nm), macrogel (20-200 um)로 구분지을 수 있습니다. [1] 이러한 하이드로젤중에서 외부 자극 (온도, pH, 빛, 자기장, 전기장)에 의해서 졸-젤 전이 (sol-gel transition)를 조절할 수 있습니다. 그 중에서도 poly(N-isoproplyacrlyamide) (PNIPAAm)은 가장 많이 연구된 온도 감응 하이드로젤로서, 32~35 ℃에서 젤화가 일어나고 식으면 다시 졸상태로 열 가역적인 젤화 특성을 가지고 있습니다. 이러한 친수성/소수성 상태의 가역성은 LCST (low critical solution temperature) 이하 또는 이상 온도를 변화시킴으로써 발생합니다.
PNIPAAm은 아래 그림과 같이 극성기인 C=O, N-H와 비극성기인 iso-proyl 기, 고분자 backbone을 가지고 있다. Cloud point를 기준으로 낮을 때는 수화된 상태로 hydrophilic state라고 불리고, 높을 때는 탈수화된 상태로 collapsed state라고 불린다. 온도가 낮을 때는 극성기가 물과 잘 상호작용을 하기 때문에 잘 녹거나 팽창되어 있는 상태이지만, 온도가 높을 때는 비극성기끼리 상호작용하는 힘이 더 크기 때문에 수축되어 불용성을 갖게 됩니다. 따라서 온도에 따라서 가역적으로 팽창과 수축을 할 수 있습니다.[2]
PNIPAAm의 LCST는 인간의 체온 (약 36.5~37.5 ℃)에 가깝고, 생체적합성을 가지고 있기 때문에 특히, PNIPAAm에 대한 많은 연구가 진행되고 있습니다. PNPAAm 하이드로젤은 라디칼 중합을 통해 중합할 수 있으며 다른 monomer와 함께 중합되어 블록 공중합체를 이룰 수 있고, 가교를 시켜 젤로도 중합할 수 있습니다. [2,3]
· Yallapu, Murali Mohan, Meena Jaggi, and Subhash C. Chauhan. "Design and engineering of nanogels for cancer treatment." Drug discovery today 16.9-10 (2011): 457-463.
· Lanzalaco, Sonia, and Elaine Armelin. "Poly (n-isopropylacrylamide) and copolymers: A review on recent progresses in biomedical applications." Gels 3.4 (2017): 36.
· Echeverria, Coro, et al. "Functional stimuli-responsive gels: Hydrogels and microgels." Gels 4.2 (2018): 54.
· Kamachi, Yuichiro, et al. "Hydrogels containing Prussian blue nanoparticles toward removal of radioactive cesium ions." Journal of nanoscience and nanotechnology 16.4 (2016): 4200-4204.
· Moon, Seongjun, et al. "Prussian blue decorated hydrogel particles for effective removal of cesium ion from aqueous media." Polymer 186 (2020): 122029.
· Oh, Daemin, et al. "Enhanced immobilization of Prussian blue through hydrogel formation by polymerization of acrylic acid for radioactive cesium adsorption." Scientific reports 9.1 (2019): 1-12.
· Fu, Guanglei, et al. "Spatiotemporally Controlled Multiplexed Photothermal Microfluidic Pumping under Monitoring of On-Chip Thermal Imaging." ACS sensors 4.9 (2019): 2481-2490.
· Fu, Guanglei, et al. "Photothermal Microfluidic Sensing Platform Using Near-Infrared Laser-Driven Multiplexed Dual-Mode Visual Quantitative Readout." Analytical chemistry 91.20 (2019): 13290-13296.
· Fu, Jijun, et al. "Prussian blue nanosphere-embedded in situ hydrogel for photothermal therapy by peritumoral administration." Acta Pharmaceutica Sinica B 9.3 (2019): 604-614.
· Sershen, S. R., et al. "Temperature‐sensitive polymer–nanoshell composites for photothermally modulated drug delivery." Journal of Biomedical Materials Research: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials 51.3 (2000): 293-298.
· Qiu, Meng, et al. "Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy." Proceedings of the National Academy of Sciences 115.3 (2018): 501-506.
· Hao, Yijun, et al. "A robust hybrid nanozyme@ hydrogel platform as a biomimetic cascade bioreactor for combination antitumor therapy." Biomaterials Science 8.7 (2020): 1830-1839.
· Liang, Yuqing, et al. "Integrated Hydrogel Platform for Programmed Antitumor Therapy Based on Near Infrared-Triggered Hyperthermia and Vascular Disruption." ACS applied materials & interfaces 11.24 (2019): 21381-21390.
· Lee, Eunsu, et al. "Photothermally driven fast responding photo-actuators fabricated with comb-type hydrogels and magnetite nanoparticles." Scientific reports 5 (2015): 15124.
· Zhu, Chun‐Hua, et al. "Photothermal poly (N‐isopropylacrylamide)/Fe3O4 nanocomposite hydrogel as a movable position heating source under remote control." Small 10.14 (2014): 2796-2800.
· Zhu, Chun‐Hua, et al. "Hydrogels: Photothermally Sensitive Poly (N‐isopropylacrylamide)/Graphene Oxide Nanocomposite Hydrogels as Remote Light‐Controlled Liquid Microvalves (Adv. Funct. Mater. 19/2012)." Advanced Functional Materials 22.19 (2012): 4016-4016.
· Ke, Xi-xian, et al. "Morphology and Thermoresponsive Behavior of Hybrid Micelles of Polystyrene-b-Poly ((N-isopropyl acrylamide)-co-(4-vinylbenzyl chloride)) with Prussian Blue." Chinese Journal of Polymer Science 33.7 (2015): 1038-1047.
· Lee, Su-Kyoung, Yongdoo Park, and Jongseong Kim. "Thermoresponsive Behavior of Magnetic Nanoparticle Complexed pNIPAm-co-AAc Microgels." Applied Sciences 8.10 (2018): 1984.
· Qi, Xiaofang, et al. "Near infrared laser-controlled drug release of thermoresponsive microgel encapsulated with Fe 3 O 4 nanoparticles." RSC advances 7.32 (2017): 19604-19610.
· Regmi, Rajesh, et al. "Hyperthermia controlled rapid drug release from thermosensitive magnetic microgels." Journal of Materials Chemistry 20.29 (2010): 6158-6163.
· Choe, Ayoung, et al. "Stretchable and wearable colorimetric patches based on thermoresponsive plasmonic microgels embedded in a hydrogel film." NPG Asia Materials 10.9 (2018): 912-922.
· Wei, Menglian, and Michael J. Serpe. "Temperature–Light Dual‐Responsive Au@ PNIPAm Core‐Shell Microgel‐Based Optical Devices." Particle & Particle Systems Characterization 36.1 (2019): 1800326.
· de Solorzano, Isabel Ortiz, et al. "Triggered drug release from hybrid thermoresponsive nanoparticles using near infrared light." Nanomedicine 15.3 (2020): 219-234.
· Chen, Yun-Sheng, et al. "Dynamic contrast-enhanced photoacoustic imaging using photothermal stimuli-responsive composite nanomodulators." Nature communications 8.1 (2017): 1-10.
· Guo, Xingmei, et al. "Grafting thermosensitive PNIPAM onto the surface of carbon spheres." Applied surface science 321 (2014): 116-125.
· Xu, Xiaohui, et al. "A near-infrared and temperature-responsive pesticide release platform through core–shell polydopamine@ PNIPAm nanocomposites." ACS Applied Materials & Interfaces 9.7 (2017): 6424-6432.
· Tan, Licheng, et al. "A novel thermal and pH responsive drug delivery system based on ZnO@ PNIPAM hybrid nanoparticles." Materials Science and Engineering: C 45 (2014): 524-529.
· Bryan, William W., et al. "Porous silver-coated pNIPAM-co-AAc hydrogel nanocapsules." Beilstein journal of nanotechnology 10.1 (2019): 1973-1982.
· Shen, Song, et al. "Near-infrared light-responsive nanoparticles with thermosensitive yolk-shell structure for multimodal imaging and chemo-photothermal therapy of tumor." Nanomedicine: Nanotechnology, Biology and Medicine 13.5 (2017): 1607-1616.
· Marpu, Sreekar Babu, et al. "Single-Step Photochemical Formation of Near-Infrared-Absorbing Gold Nanomosaic within PNIPAm Microgels: Candidates for Photothermal Drug Delivery." Nanomaterials 10.7 (2020): 1251.
· Wadajkar, Aniket S., et al. "Prostate cancer-specific thermo-responsive polymer-coated iron oxide nanoparticles." Biomaterials 34.14 (2013): 3618-3625.
· Denmark, D. J., et al. "Remote triggering of thermoresponsive PNIPAM by iron oxide nanoparticles." RSC advances 6.7 (2016): 5641-5652.
· Jaiswal, Manish K., et al. "Biocompatibility, biodistribution and efficacy of magnetic nanohydrogels in inhibiting growth of tumors in experimental mice models." Biomaterials Science 2.3 (2014): 370-380.
· Koppolu, Bhanuprasanth, et al. "Temperature-sensitive polymer-coated magnetic nanoparticles as a potential drug delivery system for targeted therapy of thyroid cancer." Journal of biomedical nanotechnology 8.6 (2012): 983-990.
· Pan, Yongzheng, et al. "Water‐soluble poly (N‐isopropylacrylamide)–graphene sheets synthesized via click chemistry for drug delivery." Advanced Functional Materials 21.14 (2011): 2754-2763.
· Rahimi, Maham, et al. "In vitro evaluation of novel polymer-coated magnetic nanoparticles for controlled drug delivery." Nanomedicine: Nanotechnology, Biology and Medicine 6.5 (2010): 672-680.
· Rahimi, Maham, et al. "Synthesis and characterization of thermo-sensitive nanoparticles for drug delivery applications." Journal of biomedical nanotechnology 4.4 (2008): 482-490.
· Zhang, Hao-Hao, et al. "Synthesis and application prospect of prussian blue coated with carboxyl chitosan hydrogel." Ferroelectrics 529.1 (2018): 100-104.
· Medeiros, Simone F., et al. "Fabrication of biocompatible and stimuli-responsive hybrid microgels with magnetic properties via aqueous precipitation polymerization." Materials Letters 175 (2016): 296-299.
· Maji, Samarendra, et al. "Poly (N-isopropylacrylamide) coated gold nanoparticles as colourimetric temperature and salt sensors." Polymer Chemistry 7.9 (2016): 1705-1710.
· Qian, Jun, et al. "A thermo-sensitive polymer network crosslinked by Prussian blue nanocrystals for cesium adsorption from aqueous solution with large capacity." Journal of Materials Chemistry A 5.42 (2017): 22380-22388.
· Wi, Hyobin, et al. "Surface modification of poly (vinyl alcohol) sponge by acrylic acid to immobilize Prussian blue for selective adsorption of aqueous cesium." Chemosphere 226 (2019): 173-182.
· Xian, Yuezhong, et al. "Preparation of poly (vinylpyrrolidone)-protected Prussian blue nanoparticles-modified electrode and its electrocatalytic reduction for hemoglobin." Analytica chimica acta 546.2 (2005): 139-146.
· Kang, Sung-Min, et al. "Microfluidic generation of Prussian blue-laden magnetic micro-adsorbents for cesium removal." Chemical Engineering Journal 341 (2018): 218-226.
· Su, Yun Yan, et al. "A multifunctional PB@ mSiO2–PEG/DOX nanoplatform for combined photothermal–chemotherapy of tumor." ACS Applied Materials & Interfaces 8.27 (2016): 17038-17046.
· Chen, Huajian, et al. "Facile synthesis of Prussian blue nanoparticles as pH-responsive drug carriers for combined photothermal-chemo treatment of cancer." RSC advances 7.1 (2017): 248-255.
· Xue, Peng, et al. "An in-vitro study of enzyme-responsive Prussian blue nanoparticles for combined tumor chemotherapy and photothermal therapy." Colloids and Surfaces B: Biointerfaces 125 (2015): 277-283.
· Chen, Huajian, et al. "Multifunctional phase-change hollow mesoporous Prussian blue nanoparticles as a NIR light responsive drug co-delivery system to overcome cancer therapeutic resistance." Journal of Materials Chemistry B 5.34 (2017): 7051-7058.
· Chen, Wansong, et al. "Cell membrane camouflaged hollow prussian blue nanoparticles for synergistic photothermal‐/chemotherapy of cancer." Advanced Functional Materials 27.11 (2017): 1605795.
· Liu, Bin, et al. "RBC membrane camouflaged prussian blue nanoparticles for gamabutolin loading and combined chemo/photothermal therapy of breast cancer." Biomaterials 217 (2019): 119301.
· Chang, Ling, et al. "Facile one-pot synthesis of magnetic Prussian blue core/shell nanoparticles for radioactive cesium removal." RSC advances 6.98 (2016): 96223-96228.
· Jiang, Tingting, et al. "Prussian blue-encapsulated Fe3O4 nanoparticles for reusable photothermal sterilization of water." Journal of colloid and interface science 540 (2019): 354-361.
· Guo, Yi-Fei, et al. "Synthesis of Mesoporous Yolk-Shell Magnetic Prussian Blue Particles for Multi-Functional Nanomedicine." Journal of nanoscience and nanotechnology 18.5 (2018): 3059-3066.
워드 
