Preparation And Properties Of Photothermally Enhanced Multi-responsive Nanogels

As one of mostly deadly diseases,cancer threatens people's lives all around the world.In China,annually,the death toll from cancer is about 2.5 million.However,the traditional methods we used in the field of medical service are not useful enough to solve this difficult problem,associated with the poor targeting capacity and low therapeutic efficacy of broad-spectrum anticancer drugs as well as several multidrug resistant mechanisms existed in cancer cells.To deal with these problems,the researchers apply themselves to synthesizing new kinds of drugs and exploring smart drug-carriers.Through injection or taking orally,drug-loaded carriers is passively transported to tumors,accelerated release the drug molecules stimulated by the special micro-environment around the tumors to realize the stable and lasting administration.There are still some problems to be solved in spite of the excellent performance of intelligent carriers.For one thing,it can't fulfill the high dosage in tumors that the passive transport and release of drugs only depends on the internal stimulus.For another,long-term accumulation of carrier materials in the body may be toxic,harmful to normal cells.In recent years,with the rapid development of nanotechnology,biocompatible nanogels with small dimensions are widely applied in the field of medical service.Herein,to develop multifunctional anticancer nanomedcines,photothermalnanogelswithmulti-stimulativeproperties,poly?N-isopropylacrylamide?/graphene oxide?PNIPAM/GO?,are synthesized in a facile approach.The physiological stability,intelligent release behaviors as well as the photothermal effect inside and outside cells were investigated in detail.Moreover,the methods to enhance the photothermal effect were studied in a systemic way.1)Preparation and synergistically intelligent release behaviors of PNIPAM/GO nanogelsReduction-sensitive PNIPAM/GO?S-S?nanogels?PG?S-S?NGs?were developed via in situ polymerizing N-isopropylacrylamide?NIPAM?initiated by KPS-NaHSO₃ in the presence of GO aqueous solution through nanoprecipitation using N,N'-bis?acryloyl?cystamine?BAC?as a reducible crosslinker and sodium dodecyl sulfate?SDS?as an emulsifer.The nanogels had a size of¹30 nm with a sphere shape and a narrow size distribution.And reduction-insensitive nanogels?PG?C-C?NGs?were crosslinked by N,N'-methylenebisacrylamide?MBA?as a control group.The physiological stability,hydrodynamic size,Zeta potential,surface morphology,degradation behavior as well as photothermal effects were evaluated.Doxorubicin?DOX?,a template drug,was encapsulated by PG NGs via a facile solution blending in the darkness to obtain PGD?S-S?NGs.The intelligent release behaviors,cytotoxicity,cellular uptake were investigated.The results showed that the physiological stability of PG NGs was improved as well as photothermal effect compared with pure GO.Meanwhile,PG?S-S?NGs displayed obvious reduction-triggered degradation compared with PG?C-C?NGs.Moreover,PGD?S-S?NGs presented an enhanced drug delivery under environments mimicking acidic/reducible solid tumor and endo-lysosomal compartments,which can be further accelerated by remote NIR photothermal radiation treatment,exerting high anticancer bioactivity.2)Preparation and synergistically intelligent release behaviors of P?NIPAM-SGO?nanogelsIn order to further improve the conversion efficiency of the nanogels,silanizated GO?SGO?was synthesized by modifying GO via silane coupling agent?KH-570?,copolymerized with NIPAM initiated by KPS-NaHSO₃ in the presence of BAC as a reducible crosslinker and SDS as an emulsifer.The obtained nanogels?P?NIPAM-SGO?,PSG NGs?had a size of¹45 nm with a sphere shape and a narrow size distribution.The obtained nanogels have higher content of GO.The comparison of photothermal effects between modified and unmodified carrier was evaluated.Meanwhile,the hydrodynamic size,Zeta potential and the drug-loading capacity of PSG NGs were also investigated.DOX was encapsulated by PSG NGs via a facile solution blending in the darkness to obtain PSGD NGs.The intelligent release behaviors,cytotoxicity,cellular uptake were studied.The results showed that the photothermal effect as well as the drug-loading capacity of PSG NGs was enhanced sharply compared with PG?S-S?NGs.Moreover,PSG NGs presented an enhanced intelligent drug release behavior.Importantly,in the intracellular study,PSGD NGs displayed incredible enhanced photothermal properties compared with PGD?S-S?NGs.