The Landscape of Nanovectors for Modulation in Cancer Immunotherapy

Abstract

Immunotherapy represents a promising strategy for the treatment of cancer, which functions via the reprogramming and activation of antitumor immunity. However, adverse events resulting from immunotherapy that are related to the low specificity of tumor cell-targeting represent a limitation of immunotherapy's efficacy. The potential of nanotechnologies is represented by the possibilities of immunotherapeutical agents being carried by nanoparticles with various material types, shapes, sizes, coated ligands, associated loading methods, hydrophilicities, elasticities, and biocompatibilities. In this review, the principal types of nanovectors (nanopharmaceutics and bioinspired nanoparticles) are summarized along with the shortcomings in nanoparticle delivery and the main factors that modulate efficacy (the EPR effect, protein coronas, and microbiota). The mechanisms by which nanovectors can target cancer cells, the tumor immune microenvironment (TIME), and the peripheral immune system are also presented. A possible mathematical model for the cellular communication mechanisms related to exosomes as nanocarriers is proposed.

Keywords: bioinspired nanovectors; immunotherapy; nanomedicine; nanoparticles; nanopharmaceuticals; nanotechnology.

Figure 1

Process of antigen release by the tumor cell is followed by processing and presentation by APCs and activation of effective immune cells. T cells are trafficking and infiltrating the tumor tissues, being activated the immune cells from the TIME (tumor-infiltrating microenvironment) (created with www.BioRender.com).

Figure 2

Classes of nanopharmaceuticals (created with BioRender—www.BioRender.com).

Figure 3

Bio-inspired nanovectors: A. Tumor destruction by cytokine/chemokine-armed oncolytic viruses. GM-CSF helps in antigen presentation through the recruitment and activation of dendritic cells and macrophages; B. Minicells with bacterial origin encapsulate the chemotherapeutic drugs, shRNA, or toxin protein. Minicells bind to the receptors of the cancer cells via the bi-specific antibody conjugated on the minicell’s surface. Minicells enter the cancer cell, where they release drugs with an anti-cancer effect. Engineered minicells can produce antigen, which activates the anti-tumor immune response; C. EVS deliver antigens to activate the immune cells or can deliver anti-tumor drugs D. VPL are attached to host receptors, inducing the binding of adaptor proteins to clathrin and releasing of the clathrin-mediated vesicles that deliver to early endosomes; E. Bacteriophages can be encapsulated into polymers and stimulate the DCs, triggering an immune response (created with Biorender—www.BioRender.com).