Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice

Raimondo, Theresa M.; Mooney, David J.

doi:10.1073/pnas.1806908115

Cited by 125 publications

(121 citation statements)

References 51 publications

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“…Interestingly, these fibres are not blocked in their growth, but they rather undergo a temporary delay, showing, after a longer time period, several fully matured fibres with peripheral nuclei. In line with our results, a recent study showed that IL4‐conjugated gold nanoparticles injected into injured murine skeletal muscle improved muscle histology and performance associated with two‐fold increase of type II macrophages …”

Section: Discussionsupporting

confidence: 92%

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Costamagna¹,

Duelen²,

Penna

et al. 2020

J cachexia sarcopenia muscle

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Background Anorexia, body wasting, inflammation, muscle, and adipose tissue loss are hallmarks of cancer cachexia, a syndrome that affects the majority of cancer patients, impairing their ability to endure chemotherapeutic therapies and reducing their lifespan. In the last 10 years, alterations of protein turnover and impairment of adult myogenesis have been proposed as major contributing factors. Methods Muscle stem cells, including satellite cells, mesoangioblasts, and fibroadipogenic progenitors, were isolated and characterized from C26 colon carcinoma‐bearing (C26) mice. Circulating levels of interleukin‐4/13 (IL4/IL13) were analysed by ELISA, and the effects of IL4 on muscle mass and function, protein synthesis, muscle regeneration, and myogenic progenitor cell number were analysed at both functional (treadmill and grip test) and molecular levels (qRT–PCR, immunofluorescence analysis, surface sensing of translation, and western blot). The Kaplan–Meier test was used to analyse the survival curve of IL4‐treated and IL4‐untreated C26 mice. Results The administration of IL4 to C26 mice rescued muscle mass by increasing protein synthesis. The IL4 treatment improved performances and prolonged survival of C26 mice. IL4 administration re‐established both number and function of satellite cells and fibroadipogenic progenitors without affecting mesoangioblasts in C26 mice, rescuing myogenesis. Upon IL4 treatment, a high number of cytotoxic lymphocytes and type II macrophages were observed with a subsequent increase in necrotic areas of C26 tumours. Conclusions The results here presented shed new light on IL4 signalling during muscle wasting and early stages of muscle regeneration that explain the beneficial effect observed in IL4‐treated C26 mice. These findings might aid to develop therapeutic approaches to improve mobility and quality of life in cachectic patients.

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Section: Discussionsupporting

confidence: 92%

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Costamagna¹,

Duelen²,

Penna

et al. 2020

J cachexia sarcopenia muscle

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“…While the backpacks described here bind to macrophage surfaces, other designs can be conceived to attach to other circulatory cells with higher chemotactic sensitivity (17,18,55). Also, a range of immunomodulatory payloads can be considered, including those that facilitate adaptive immune responses toward a backpack-based vaccine (52) or promote anti-inflammatory phenotypes to aid in tissue regeneration or repair for autoimmune diseases (56,57). PDMS template preparation PDMS templates were prepared by soft lithography using methods similar to those described previously (16).…”

Section: Discussionmentioning

confidence: 99%

Cellular backpacks for macrophage immunotherapy

et al. 2020

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Adoptive cell transfers have emerged as a disruptive approach to treat disease in a manner that is more specific than using small-molecule drugs; however, unlike traditional drugs, cells are living entities that can alter their function in response to environmental cues. In the present study, we report an engineered particle referred to as a “backpack” that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Backpacks evade phagocytosis for several days and release cytokines to continuously guide the polarization of macrophages toward antitumor phenotypes. We demonstrate that these antitumor phenotypes are durable, even in the strongly immunosuppressive environment of a murine breast cancer model. Conserved phenotypes led to reduced metastatic burdens and slowed tumor growths compared with those of mice treated with an equal dose of macrophages with free cytokine. Overall, these studies highlight a new pathway to control and maintain phenotypes of adoptive cellular immunotherapies.

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“…In 2018, the same group conjugated chemotherapeutic agents to the spiky gold nanoparticles to achieve chemo‐photothermal combination therapy, which generated free antigens and induced potent antitumor immunity against disseminated tumors . In the same year, Mooney and co‐workers synthesized IL‐4‐conjugated gold nanoparticles to manipulate macrophage phenotypes for muscle function recovery . The authors showed that infiltrating macrophages can be repolarized from M1 to M2 phenotypes in a superior manner compared to empty vesicles and soluble IL‐4, establishing the utility of gold nanoparticles for inflammatory injuries and diseases.…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice

Cited by 125 publications

References 51 publications

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Interleukin‐4 administration improves muscle function, adult myogenesis, and lifespan of colon carcinoma‐bearing mice

Cellular backpacks for macrophage immunotherapy

Materials for Immunotherapy

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