CaCO3-assistant synthesis of pH/near-infrared light-responsive and injectable sodium alginate hydrogels for melanoma synergistic treatment

Melanoma is an aggressive tumor located in skin with high rates of recurrence and metastasis. Due to the limited traditional therapies, the development of novel strategies against melanoma is urgently quested. To reduce the side effects of traditional administration ways and amplify the killing effect, an injectable sodium alginate (SA)-based hydrogels were developed, in which CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) were embedded for the synergistic photothermal/calcium ions interference therapy of melanoma. In the study, the formation conditions and mechanical properties of CaCO3/PDA-SA hydro -gels were characterized, and their antitumor efficiency and mechanism against mouse melanoma cells were investigated. When injected intratumorally, CaCO3/PDA-SA fluid was converted into hydrogel in situ through the interaction of pH-sensitive released Ca2+ and alginate chains, which increased the retention time of photothermal agents (CaCO3/PDA NPs) at tumor sites and thereby was more conducive to produce hyperthermia via photothermal conversion to combat melanoma. Moreover, in acidic tumor microenvironment, the residual CaCO3/PDA NPs in hydrogels continuously decomposed and released Ca2+ to destroy the Ca2+ buffering capacity and evoke the mitochondrial Ca2+-overloading, resulting in the inhibition of adenosine triphosphate production to accelerate cell death. Notably, besides the heat eleva-tion, the near-infrared light (NIR) irradiation would further enhance the release of Ca2+ to promote the Ca2'-involved cell death. Therefore, a pH/NIR-responsive and injectable SA-based hydrogels were suc-cessfully established and showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

An injectable sodium alginate (SA)-based hydrogel embedded with CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) was developed for the synergistic photothermal/calcium ions interference therapy of melanoma. The fluid was converted into a hydrogel in situ, increasing the retention time of photothermal agents at tumor sites and promoting hyperthermia. The residual CaCO3/PDA NPs continuously released Ca2+ in the acidic tumor microenvironment, leading to mitochondrial Ca2+-overloading and cell death. This pH/NIR-responsive and injectable SA-based hydrogel showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.