Nanosonosensitizer-Augmented Sonodynamic Therapy Combined with Checkpoint Blockade for Cancer Immunotherapy

Abstract

Introduction Sonodynamic therapy (SDT) has good targeting and non-invasive advantages in the treatment of solid cancers, and checkpoint blockade immunotherapy is also a promising treatment to cure cancer. However, their antitumor effects are not sufficient due to some inherent factors. Some studies that combined SDT with immunotherapy or nanoparticles have managed to enhance its efficiency to treat cancers. Methods In this work, an effective therapeutic strategy that can potentiate the antitumor efficacy of anti-PD-L1 antibody (aPD-L1) is developed by the use of cascade immuno-sonodynamic therapy (immuno-SDT). Titanium dioxide (TiO 2 ), a nanostructured agent for SDT, sonosensitizer Chlorin e6 (Ce6), and immunological adjuvant CpG oligonucleotide (CpG ODN), are used to construct a multifunctional nanosonosensitizer (TiO 2 -Ce6-CpG). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of TiO 2 -Ce6-CpG under ultrasound (US) treatment. Results The characterization tests showed that the nanosonosensitizers are polycrystalline structure with homogeneous sizes, resulting in a good drug loading efficiency. The innovative nanosonosensitizers (TiO 2 -Ce6-CpG) can not only effectively inhibit tumor growth but also stimulate the immune system to activate the adaptive immune responses, using the TiO 2 -Ce6 to augment SDT and the immune adjuvant CpG to enhance the immune response. After combined with the aPD-L1, the synergistic effect could not only efficiently inhibit the primary tumor growth but also lead to an inhibition of the non-irradiated pre-existing distant tumors by inducing a strong tumor-specific immune response. Conclusion In this study, we present an effective strategy for tumor treatment by combining nanosonosensitizer-augmented SDT and aPD-L1 checkpoint blockade. This work provides a promising strategy and offers a new vision for treating malignant tumors.

Combination of Ablation and Immunotherapy for Hepatocellular Carcinoma: Where We Are and Where to Go

“…Moreover, SP94-PB-SF-Cy5.5 and PCN-ACF-CpG@HA, in combination with PD-L1 blockade and an immunologic adjuvant (CpG), enhanced the PTT-and PDT-induced weak immunogenic cell death of cancer cells. Similarly, these strategies for enhanced immune responses also applied sonodynamic immunotherapy as recently reported by Tan et al (149) and Lin et al (150). Moreover, anti-TGF-b antibody modification is an active targeting strategy that enhances cell endocytosis for improved PTT and an immunotherapeutic strategy for immune activation (151).…”

“…( 149 ) and Lin et al. ( 150 ). Moreover, anti-TGF-β antibody modification is an active targeting strategy that enhances cell endocytosis for improved PTT and an immunotherapeutic strategy for immune activation ( 151 ).…”

The crosstalk between sonodynamic therapy and autophagy in cancer

“… Yue et al (2019) combined noninvasive SDT with checkpoint blockade immunotherapy by the nanosonosensitizers HMME/R837@Lip to induce an anti-tumour response, and this combination arrested primary tumor progression and prevented lung metastasis. Other nanocarriers combining SDT with immunotherapy were also developed, such as TIR@FITC-Nrf2-siRNA ( Wan et al, 2021 ), TiO 2 -Ce6-CpG ( Lin et al, 2021 ), PEG-CDM-aPD-L1/Ce6 ( Huang et al, 2021 ) and this combinatorial tumor therapeutics can robust anti-cancer immunity and long-term immune memory ( Table 3 ).…”

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

“…In vitro and in vivo administration activated strong immune responses with TiO 2 -Ce6 augmented SDT and the immune adjuvant CpG to increase the immune response not for only preventing tumor development but also lead to an inhibition of the nonirradiated pre-existing tumors by tempting a strong tumor-specific immune response. TiO 2 -Ce6-CpG super combination directed a new vision for treating malignant tumors . Thereby, SDT combined with the tumor immunotherapy strategy also offers long-term immunological memory function, which can protect against tumor rechallenge after elimination of the initial tumors.…”