Preparation And Anti-Tumor Properties Of Cobalt-Tin Sulphide/Selenide Composite Hydrogels

Photothermal therapy（PTT）is a highly effective,non-invasive treatment and one of the most promising strategies for treating malignant tumors.However,the high temperatures generated during treatment may activate biological immune responses that compromise treatment efficacy.Although the irradiation power of PTT can be reduced,the insufficient temperature may not kill tumor cells completely.In addition,the penetration depth of the near-infrared laser used in PTT is still insufficient due to the extensive scattering by biological tissues,making the treatment less effective,and combining PTT with other therapies may be an ideal direction for development.Sonodynamic therapy（SDT）is a promising cancer therapy that can compensate for the lack of penetration depth of PTT due to its advantages of non-invasiveness,negligible side effects and deep tissue penetration.Gas therapy（GT）is a"green"approach to cancer treatment based on the use of gas carriers to induce cancer cell death.However,if the gas concentration is too low,the therapeutic effect is compromised,while if the gas concentration is too high,the organism is damaged.When a single gas is used for treatment,the inhibitory effect on tumor growth is very limited,and tumor cells can protect themselves from death by activating the anti-death pathway.Therefore,it is important to develop a variety of gas combination strategies while achieving controlled release.In addition,GT significantly enhanced PTT.The combination of PTT,SDT and GT multi-mode therapy not only reduces the dose and radiation power of the therapeutic agent,but also improves the penetration depth of the tumor to realize the enhancement of PTT,thus achieving the purpose of better tumor elimination.On this basis,cobalt hydroxystannate（Co Sn（OH）₆）was used as the a precursor system for the preparation of cobalt-tin sulphide/selenide complex hydrogels.Cobalt-tin sulphide/selenide is a kind of homogeneous perovskite hydroxide nanocube,which has the advantages of stable crystal structure and simple synthesis method,and has a wide application prospect in catalysis and electrochemical sensors.Hydrogels have the advantages of achieving drug release and promoting wound healing.Based on Co Sn（OH）₆ nanomaterials,a cobalt-tin sulphide/selenide composite hydrogel was constructed for the combined treatment of PTT,SDT and GT in tumors.The specific research contents are as follows:（1）Co Sn（OH）₆ nanocubes were obtained by co-precipitation of Co²⁺,Sn⁴⁺and sodium citrate in alkaline solution.Hollow Co Sn（OH）₆ nanoparticles were then synthesised by etching them with sodium hydroxide（Na OH）solutions of different concentrations.Then,S element,Se element and hollow Co Sn（OH）₆ nanoparticles were ground and mixed in a certain ratio and calcined at different temperatures（300℃,450℃,600℃）in a tube furnace to obtain Co Sn S_x and Co Sn Se_x nanoparticles at different calcination temperatures.The results showed that the cobalt-tin sulphide/selenide prepared at 450℃showed strong optical absorption and good photothermal properties under the near-infrared laser irradiation at 808 nm,and could be used as a good photothermal conversion material for tumor treatment.（2）Chitosan（CTS）,carboxymethyl cellulose（CMC）and L-arginine（L-Arg）were added to the Co Sn S_x aqueous solution to construct injectable cobalt-tin sulphide composite hydrogels for the combined treatment of PTT,SDT and double GT.Under the action of ultrasound,Co Sn S_x nanoparticles can generate a large amount of singlet oxygen（¹O₂）to achieve SDT.The S element and L-Arg contained in the composite hydrogel realise the controlled release of H₂S and NO gas under acidic conditions,and can promote GT under the action of near-infrared laser and ultrasound.Taking mouse breast cancer cells as the research object,the cobalt-tin sulphide complex hydrogel has obvious inhibitory effect on mouse breast cancer cells under the double action of near infrared laser and ultrasound.This multifunctional injectable hydrogel system enhances PTT by SDT and double GT,realizing the efficient treatment of tumor.（3）Injectable cobalt-tin selenide complex hydrogels were prepared by adding sodium alginate（SA）,polyacrylamide（PAM）and diallyl trisulfide（DATS）to Co Sn Se_xaqueous solution.The results show that Co Sn Se_x with hollow structure can not only generate a large number of reactive oxygen species（ROS）under ultrasonic irradiation,but also produce H₂Se gas under acidic environment to achieve SDT and GT.Under the stimulation of near-infrared laser and ultrasound,cobalt-tin selenide composite hydrogel can realize the controlled release of H₂S and H₂Se gas,and double GT improves PTT.In addition,cobalt-tin selenide complex hydrogel showed good photothermal conversion performance under 808 nm laser irradiation,and could be used for tumor PTT.For mouse breast cancer cells,injectable cobalt-tin selenide complex hydrogel has great lethal effect on breast cancer cells under the synergistic action of near-infrared laser and ultrasound,and has significant synergistic anti-tumor effect.