Injectable Hydrogel Containing TiO Nanosheets for Synergistic Photothermal/Thermodynamic Therapy

Tumorshave become the biggest obstacle to human health,and thereare various treatment methods at present. Photothermal therapy (PTT)is usually ineffective and does not inhibit tumor progression dueto the inability of the lasers to penetrate deeply. Therefore, mostexisting studies chose a 1064 nm laser with stronger penetrating power;meanwhile, studies have shown that the inclusion of harmful free radicalscan significantly improve the antitumor efficacy. Herein, TiO nanosheets(NSs) were creatively prepared and encapsulated with an alkyl radicalgenerator {2,2 & PRIME;-azobis[2-(2-imidazoline-2-yl)propane] dihydrochloride,[AIPH]} in sodium alginate (ALG) hydrogel for effective tumor killingby PTT and pairing with dangerous free radicals. TiO NSs were obtainedby the liquid-phase exfoliation method, together with AIPH, whichwere in situ coencapsulated multifunctional hydrogels formed by thecombination of Ca2+ and ALG. This ALG hydrogel could enrichTiO NSs and AIPH at the tumor site for a long time, and through theexcellent photothermal properties of TiO NSs, AIPH could slowly andeffectively generate alkyl radicals at the tumor site, which, in turn,gave it a better antitumor effect compared with that of TiO NSs inthe deep hypoxic environment of the tumor. The AIPH + TiO + ALG hydrogelhas distinctive anticancer capabilities based on the results of both in vivo and in vitro experiments. Thismaterial also has good biosafety. By combining PTT and free radicaltreatment, this work provides a novel therapeutic method to achieveoxygen-independent free radical production and enhance therapeuticefficacy.

Automated summary

Tumors pose a significant threat to human health, and there are various treatment methods available. Photothermal therapy (PTT) is commonly ineffective due to limited penetration depth of lasers. In this study, TiO nanosheets (NSs) were prepared and encapsulated with an alkyl radical generator (AIPH) in a sodium alginate (ALG) hydrogel for effective tumor killing through PTT and free radicals. The ALG hydrogel allowed prolonged retention of TiO NSs and AIPH at the tumor site, and AIPH slowly generated alkyl radicals in the deep hypoxic tumor environment, leading to enhanced antitumor efficacy. The AIPH+TiO+ALG hydrogel demonstrated promising anticancer capabilities in both in vivo and in vitro experiments.