Synthesis Of Bi₂Se₃@mSiO₂-PEG Nanoparticles For Thermo-chemo Therapy Of Cancer Cells

Chemotherapy has been clinically accepted as one of the most commonly used and effective methods for antitumor treatments.However,due to the lack of targeting and the poor bioavailability after high-dose systemic administration,traditional chemotherapy can inevitably lead to unsatisfed outcomes with serious side effects.Recently,numerous efforts have been devoted to the development of various nanocarriers,such as liposomes,dendrimers,and silica nanostructures,for targeted drug delivery into tumors.Employing“smart”nanoparticles as drug delivery systems in response to stimuli,e.g.,the acidic pH,temperature or the light stimulation,has become a promising way to improve the effcacy of chemotherapy,thanking the on-demand drug release with spatial and real-time control.Although significantly improved biodistribution and bioavailability have been realized,the developed carriers are to a large extent confned by low drug loading and/or the fact that carriers themselves are not therapeutically active which may cause undesired side effects.Herein,we report the synthesis and biomedical application of a multifunctional drug-delivery nanoplatform for synergistic photothermal?PTT?and chemotherapy with IRT imaging based on mesoporous silica-coated Bi₂Se₃ nanoparticles?Bi₂Se₃@mSiO₂ NPs?.First,we synthesized a typical core–shell structure with the Bi₂Se₃ nanoplates as the core and mesoporous silica as the shell,and then modifed with polyethylene glycol?PEG?.Originated from the core?Bi₂Se₃@m SiO₂-PEG NPs?,the resultant Bi₂Se₃@mSi O₂-PEG NPs show strong NIR absorption,high photothermal conversion capacity,and stability.Upon NIR laser irradiation,the Bi₂Se₃@m SiO₂-PEG NPs can provide high-contrast IRT imaging and effcient photothermal killing effect on cancer cells,as confrmed by both the live-dead cell staining and CCK-8 assay.Compared with the bare Bi₂Se₃ nanoplates,the successful surface coating of m SiO₂ can not only largely improve their storage stability but also endow the NPs high drug loading capacity.Finally,by loading doxorubicin?DOX,a clinical-used chemotherapeutic drug?into the Bi₂Se₃@mSi O₂-PEG NPs via the nanoprecipitation method,the high loading capability of the cargo is demonstrated.The obtained Bi₂Se₃@m SiO₂-PEG/DOX NPs exhibit a bimodal on-demand pH-and NIR-responsive drug release manner,and can realize efficient intracellular drug delivery for chemotherapy.Most importantly a prominent synergistic therapeutic effect on cancer cells is achieved through the combination of PTT and chemotherapy,showing a signifcantly improved effcacy than either monotherapy alone.Therefore,this multifunctional and high-load Bi₂Se₃@mSiO₂-PEG NPs fabricated by the facile method could act as a“smart”drug-delivery nanosystem for multiple therapeutic treatments and diagnose on anticancer treatments.