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Introduction: Although various therapies have been adopted to treat cancer, metastasis of tumor cells still is a big challenge that compromises therapeutic benefits.Methods: We herein report an injectable drug-loaded hybrid hydrogel that can achieve sonodynamic therapy (SDT) and chemodyanmic therapy (CDT) combined action and suppression of tumor metastasis. This alginate (ALG)-based hydrogel (termed as AMPS) contains manganese dioxide (MnO2) nanoparticles as the CDT agents, an organic polymer as the sonosensitizer, and a SIS3 drug as metastasis inhibitor.Results: AMPS is formed via the chelation of ALG by Ca2+ in tumor microenvironment, in which MnO2 nanoparticles mediate CDT via Fenton-like reaction and the organic polymers enable SDT under ultrasound (US) irradiation by generating singlet oxygen (1O2), allowing for combinational action of CDT and SDT. In addition, SIS3 is released from AMPS hydrogels to inhibit the metastasis of tumor cells. As such, the AMPS enables a combinational action of SDT and CDT to greatly inhibit the growths of subcutaneous tumors in living mice and also completely suppress the tumor metastasis in lungs and livers.Conclusion: This study thus offers a hybrid hydrogel platform for combinational therapy and metastasis suppression simultaneously.

Hepatic carcinoma is one of the most common cancers worldwide, while its treatment remains a great challenge. Traditional therapeutic methods often have disadvantages such as limited therapeutic efficacy and potential side effects. In this study, we report the construction of bovine serum albumin (BSA)–stabilized manganese oxide (MnO2)/semiconducting polymer (SP) nanocomposites to combine photothermal therapy (PTT) and chemodynamic therapy (CDT) for treatment of hepatic carcinoma in living mouse models. Such nanocomposites are composed of BSA, SP, and MnO2 as the stabilizer, PTT, and CDT agent, respectively. SP produced local heat under near-infrared (NIR) laser irradiation for PTT, and MnO2 nanoparticles mediated CDT in the tumor microenvironment, leading to apoptosis of cancer cells. Such nanocomposite-mediated combinational therapy showed a much higher efficacy in inhibiting growth of subcutaneous HepG2 tumors in nude mice than sole treatment. This study thus provides a multifunctional nanoplatform for safe and effective treatment of hepatic carcinoma.

Immunotherapy is a promising therapeutic strategy for cancer, while it has been demonstrated to encounter the issues of low immune responses and underlying immune-related adverse events. The sonodynamic therapy (SDT) that utilizes sonosensitizers to produce reactive oxygen species (ROS) triggered by ultrasound (US) stimulation can be used to ablate tumors, which also leads to the induction of immunogenic cell death (ICD), thus achieving SDT-induced immunotherapy. Further combination of SDT with immunotherapy is able to afford enhanced antitumor immunity for tumor regression. In this mini review, we summarize the recent development of nanosonosensitizers with US-induced ROS generation for cancer SDT immunotherapy. The uses of nanosonosensitizers to achieve SDT-induced immunotherapy, combinational therapy of SDT with immunotherapy, and combinational therapy of SDT with multiple immunotherapies are briefly introduced. Furthermore, the current concerns and perspectives for the development and further clinical applications of these nanosonosensitizers for SDT-combined immunotherapy of cancer are discussed.