Liquid Metal Nanoplatform Based Autologous Cancer Vaccines

Abstract

Therapeutic cancer vaccines have been vigorously sought to bolster host adaptive immunity against metastatic cancers, but tumor heterogeneity, ineffective antigen utilization, and immunosuppressive tumor microenvironment hinder their clinical applications. Autologous antigen adsorbability and stimulus-release carrier coupling with immunoadjuvant capacity are urgent for personalized cancer vaccines. Here, we propose a perspective strategy of using a multipotent gallium-based liquid metal (LM) nanoplatform for personalized in situ cancer vaccines (ISCVs). The antigen-capturing and immunostimulatory LM nanoplatform can not only effectively destroy orthotopic tumors to generate multifarious autologous antigens upon external energy stimulation (photothermal/photodynamic effect) but also capture and transport antigens into dendritic cells (DCs) to enhance antigen utilization (adequate DCs uptake, antigen-endo/lysosomal escape) and facilitate DCs activation (mimic alum immunoadjuvant capacity), which ultimately awaken systemic antitumor immunity (expand cytotoxic T lymphocytes and modulate tumor microenvironment). With immune checkpoint blockade (anti-PD-L1) to further relieve the immunosuppressive tumor microenvironment, the positive tumoricidal immunity feedback loop was established to effectively eliminate orthotopic tumors, inhibit abscopal tumor growth, relapse, and metastasis as well as tumor-specific prevention. Collectively, this study demonstrates the potential of a multipotent LM nanoplatform for personalized ISCVs, which will open frontier exploration of LM-based immunostimulatory biomaterials and may encourage further investigation of precise individualized immunotherapy.

Nanocatalytic Anti‐Tumor Immune Regulation

“…[57] These antigens are not or lowly expressed in normal cells and therefore can initiate specific immune responses against tumor cells. [58] The above antigens can be released into the microenvironment by injured tumor cells, phagocytosed by dendritic cells and macrophages, and presented on the cell surface together with MHC molecules. [59] This process transforms the tumor into a "hot tumor" and activates T lymphocytes to initiate subsequent adaptive immunity and immune memory.…”

Nanodelivery Systems as a Novel Strategy to Overcome Treatment Failure of Cancer

“…With immune checkpoint blockade (anti-PD-L1) further alleviating the immunosuppressed tumor microenvironment, a positive tumor-killing immune feedback loop was established to effectively remove tumors in situ, inhibiting distant tumor growth, recurrence, and metastasis, achieving tumor-specific prevention. [202]…”

Radioactive Hydroxyapatite Microspheres Empower Sustainable In Situ Tumor Vaccination

“…Andrew et al proposed utilizing the surface chemical properties of nanoparticles to capture antigens and enhance the antitumor immune response during radiotherapy . Since then, various materials have been designed specifically for antigen capture, which can also serve as adjuvants to enhance antigen effects. , For example, a recent approach involves using cationic polymer-modified flagellate bacteria to capture radiotherapy-released antigens for facilitating ISV . Additionally, some materials with imaging capabilities can track the fate of vaccines in vivo .…”