Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy

Abstract

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

Stimuli-Responsive Polymersomes: Reshaping the Immunosuppressive Tumor Microenvironment

“…To systematically evoke adaptive immunity, nanovaccines need to be drained to lymph nodes along with carrying tumor antigens, which may compromise the needs for intravenous infusion and/or on demand drug release. However, the immunosuppressive TME provides the feasibility for stimuli-responsive nanocarrier to targeted on demand modulation by targeted delivery of immunotherapeutic eliciting both innate and adaptive antitumor immunity. − Similarly, either the passive or active targeting to tumor tissues could significantly improve the therapeutics accumulation in the TME, which provides the feasibility for immunoregulatory therapeutics delivery. − The notable distinctions between the tumor and normal tissue, such as acidic pH, altered redox potential, and upregulated enzymes, can be leveraged as the endogenous-stimuli for the design of nanomedicine. − Polymersomes, also known as polymeric vesicles, are assembled from amphiphilic block or graft copolymers and share features similar to those of liposomes, exhibiting a hollow structure surrounded by bilayer membranes that enable the delivery of nucleic acids and proteins. In addition, the higher molecular weight of polymers compared to lipids significantly enhances the mechanical properties and stability of polymersomes.…”