Activatable Cancer Sono‐Immunotherapy using Semiconducting Polymer Nanobodies

Abstract

Despite the great promises of sonodynamic therapy (SDT) in combination cancer therapy, its clinical applications are hindered by the “always‐on” pharmacological activities of therapeutic agents and the lack of efficient sonosensitizers. Herein, the development of semiconducting polymers as efficient sonosensitizers and further development of sono‐immunotherapeutic nanobodies (SPNAb) for activatable cancer sono‐immunotherapy are reported. Conjugation of anti‐CTLA‐4 antibodies onto the polymer nanoparticles through a 1O2‐cleavable linker affords SPNAb with relatively low CTLA‐4 binding affinity. Upon sono‐irradiation, SPNAb generates 1O2 not only to elicit a sonodynamic effect to induce immunogenic cell death, but also to release anti‐CTLA‐4 antibodies and trigger in situ checkpoint blockade. Such a synergistic therapeutic action mediated by SPNAb modulates the tumoricidal function of T‐cell immunity by promoting the proliferation of cytotoxic T lymphocytes and depleting immunosuppressive regulatory T cells, resulting in effective tumor regression, metastasis inhibition, durable immunological memory, and prevention of relapse. Therefore, this study represents a proof‐of‐concept sonodynamic strategy using semiconducting polymers for precise spatiotemporal control over immunotherapy.

Oral Nanomotor‐Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo‐Sono‐Immunotherapy against Colon Cancer

“…1 O 2 has been recognized as a main cause of US-mediated death of tumor cells. [42,43] Accordingly, 2′,7′-dichlorofluorescein diacetate (DCFH-DA) was utilized to determine the intracellular ROS based on the generated green fluorescence signals from 2′,7′-dichlorofluorescein (DCF) converted from DCFH-DA in the presence of ROS. [44,45] Figure S10a, Supporting Information, revealed that the negative green fluorescence signals detected from the control cells (without treatment) were indicative of low concentrations of intracellular ROS.…”

Application of nanosonosensitizer materials in cancer sono-dynamic therapy

“…The combination of SDT with other cancer treatments has shown great potential as a new tumor treatment strategy. 21,109 In this section, we broadly summarize and discuss several SDT-based combination therapy strategies, including chemotherapy, photodynamic therapy (PDT), chemodynamic therapy (CDT), immunotherapy, and photothermal therapy (PTT) (Table 3).…”

NIR‐II Excitation Phototheranostic Platform for Synergistic Photothermal Therapy/Chemotherapy/Chemodynamic Therapy of Breast Cancer Bone Metastases

“…[26] A variety of NIR-II absorption or NIR-II fluorescence agents, such as gold nanomaterials, copper sulfide nanomaterials, and conjugated polymers (CPs), have been developed as NIR-II excitation multifunctional phototheranostic agents. [27] In comparison with metal nanomaterials, organic CPs possess the salient advantages of outstanding biocompatibility and ease of processability, [28] and hence, they have generated tremendous interest among NIR-II PTT/chemotherapy, NIR-II PTT/gas therapy, and NIR-II PTT/CDT researchers. [29] Nevertheless, there are two major challenges for CP-based phototheranostics that compromise their clinical applicability.…”