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Stimulating antitumor immunity with nanoparticles

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A variety of strategies, have been applied to cancer treatment and the most recent one to become prominent is immunotherapy. This interest has been fostered by the demonstration that the immune system does recognize and often eliminate small tumors but tumors that become clinical problems block antitumor immune responses with immunosuppression orchestrated by the tumor cells. Methods to reverse this tumor‐mediated immunosuppression will improve cancer immunotherapy outcomes. The immunostimulatory potential of nanoparticles (NPs), holds promise for cancer treatment. Phagocytes of various types are an important component of both immunosuppression and immunostimulation and phagocytes actively take up NPs of various sorts, so NPs are a natural system to manipulate these key immune regulatory cells. NPs can be engineered with multiple useful therapeutic features, such as various payloads such as antigens and/or immunomodulatory agents including cytokines, ligands for immunostimulatory receptors or antagonists for immunosuppressive receptors. As more is learned about how tumors suppress antitumor immune responses the payload options expand further. Here we review multiple approaches of NP‐based cancer therapies to modify the tumor microenvironment and stimulate innate and adaptive immune systems to obtain effective antitumor immune responses.

Advantages of NPs used as therapeutic regimens for cancer therapy. Use of NPs with potent adjuvant activity or TLR ligand‐encapsulated NPs as a platform to efficiently deliver tumor antigen to APCs can generate optimal delivery of tumor antigen and full activation of APCs that result in an effective adaptive immune response. The immunostimulatory activity of NPs is capable of inducing secretion of inflammatory cytokines, such as TNF‐α, IL‐12, and IFN‐γ, which are crucial for stimulation of T cells and recruitment of NK cells. Inclusion of targeting ligands on the surface of NPs can cause selective destruction of tumor cells. NP‐mediated delivery of chemotherapeutic drugs can offer effective drug delivery and controlled release, leading to enhanced safety and improved chemotherapy efficacy for tumor treatment. NP, nanoparticle; DC, dendritic cell; APC, antigen‐presenting cell; NK, natural killer; TLR, toll‐like receptor.
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Schematic diagram of structure of NP platforms for therapeutic applications including surface modification, toll‐like receptor (TLR) ligands, targeting ligands, tumor antigen load, and payload composed of therapeutic entities. NP, nanoparticle; TLR, toll‐like receptor.
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Schematic overview of the immune response elicited by a therapeutic NP. NP uptake by immature APCs after encounter with NPs or TLR ligand‐conjugated NPs entrapped with tumor antigens induces efficient delivery of antigen to APCs. Maturation and upregulation of co‐ stimulatory molecules CD80, CD86, and CD40 following antigen uptake and processing within APCs promotes their migration to lymph nodes where they can activate T cells. Cross presentation of tumor antigens through MHC class I and class II on APCs to CD8+ or CD4+ T cells, respectively, stimulates T cells. CD8+ T cells undergo proliferation and differentiate into CTLs whereas CD4+ T cells differentiate into T‐helper 1 (Th1) cells that can enhance antitumor CTL immune response at the tumor site. CTLs can cause tumor destruction by direct lysis of tumor cells. NP, nanoparticle; APC, antigen‐presenting cell; TLR, toll‐like receptor; DC, dendritic cell; ER, endoplasmic reticulum; MHC, major histocompatibility complex; TCR, T cell receptor; CTL, cytotoxic T lymphocyte; Th1, T‐helper 1.
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Mauro Ferrari

Mauro Ferrari

started out in mechanical engineering and became interested in nanotechnology with his studies on nanomechanics and nanofluidics. His research work and involvement with setting up some of the premier nano centers and alliances in the world, bringing together universities, hospitals, and federal agencies, showcases interdisciplinarity at work.

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