Immunosuppressive and anti‐inflammatory properties of engineered nanomaterials

Ilinskaya, Anna; Dobrovolskaia, Marina A.

doi:10.1111/bph.12722

Cited by 94 publications

(67 citation statements)

References 128 publications

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“…In fact, uptake of liposomes by peritoneal macrophage can induce a tolerogenic M2-like phenotype [15]. The production of TGFβ by these tolerogenic myeloid cells can lead to secondary release of CeC motif chemokine ligand 2 (CCL2, also known as monocyte chemotactic protein 1 [MCP-1]) and emigration of immature myeloid cells from the bone marrow into circulation and organs of the MPS such as spleen [60,76] (Fig. 8).…”

Section: Discussionmentioning

confidence: 99%

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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Liposomal nanoparticles are the most commonly used drug nano-delivery platforms. However, recent reports show that certain pegylated liposomal nanoparticles (PLNs) and polymeric nanoparticles have the potential to enhance tumor growth and inhibit antitumor immunity in murine cancer models. We sought herein to identify the mechanisms and determine whether PLN-associated immunosuppression and tumor growth can be reversed using alendronate, an immune modulatory drug. By conducting in vivo and ex vivo experiments with the immunocompetent TC-1 murine tumor model, we found that macrophages were the primary cells that internalized PLN in the tumor microenvironment and that PLN-induced tumor growth was dependent on macrophages. Treatment with PLN increased immunosuppression as evidenced by increased expression of arginase-1 in CD11b+Gr1+ cells, diminished M1 functionality in macrophages, and globally suppressed T-cell cytokine production. Encapsulating alendronate in PLN reversed these effects on myeloid cells and shifted the profile of multi-cytokine producing T-cells towards an IFNγ+ perforin+ response, suggesting increased cytotoxic functionality. Importantly, we also found that PLN-encapsulated alendronate (PLN-alen), but not free alendronate, abrogated PLN-induced tumor growth and increased progression-free survival. In summary, we have identified a novel mechanism of PLN-induced tumor growth through macrophage polarization and immunosuppression that can be targeted and inactivated to improve the anticancer efficacy of PLN-delivered drugs. Importantly, we also determined that PLN-alen not only reversed protumoral effects of the PLN carrier, but also had moderate antitumor activity. Our findings strongly support the inclusion of immune-responsive tumor models and in-depth immune functional studies in the preclinical drug development paradigm for cancer nanomedicines, and the further development of chemo-immunotherapy strategies to co-deliver alendronate and chemotherapy for the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Rajan

Sabnani

Mavinkurve

et al. 2018

Journal of Controlled Release

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“…For example, dexamethasone-loaded PLGA nanoparticles can be combined with siRNA-targeting COX-2 to suppress inflammatory responses (Park et al, 2012). More examples illustrating the benefits of delivering immunosuppressive and anti-inflammatory drugs using nanoparticles have been recently reviewed elsewhere (Ilinskaya and Dobrovolskaia, 2014). …”

Section: Achievementsmentioning

confidence: 99%

Current understanding of interactions between nanoparticles and the immune system

Dobrovolskaia

Shurin

Shvedova

2016

Toxicology and Applied Pharmacology

253

189

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The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other endpoints, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles’ physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials.

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“…Therapeutic NPs for these purposes need to have immunosuppressive or anti-inflammatory properties [77]. Engineered NPs as vehicles are designed to deliver anti-inflammatory compounds to phagocytes, reducing the therapeutic dose and immune based side effects.…”

Section: Therapeutic Immune Modulation By Engineered Nanoparticlesmentioning

confidence: 99%

Effects of engineered nanoparticles on the innate immune system

Liu

Hardie

Zhang

et al. 2017

Seminars in Immunology

222

131

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Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy.

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Immunosuppressive and anti‐inflammatory properties of engineered nanomaterials

Cited by 94 publications

References 128 publications

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Liposome-induced immunosuppression and tumor growth is mediated by macrophages and mitigated by liposome-encapsulated alendronate

Current understanding of interactions between nanoparticles and the immune system

Effects of engineered nanoparticles on the innate immune system

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