Manganese-Based Nanoactivator Optimizes Cancer Immunotherapy <i>via</i> Enhancing Innate Immunity

Hou, Lin; Tian, Chunyu; Yan, Yingshan; Zhang, Lewen; Zhang, Huijuan; Zhang, Zhenzhong

doi:10.1021/acsnano.9b06111

Cited by 215 publications

(163 citation statements)

References 50 publications

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“…The fixation cGAMP with Mn 2+ ion not only improved the stability of Mn‐cGAMP NVs, but also potentiated the activation of STING. [ 8 ] After intratumoral injection (i.t.) of Mn‐cGAMP NVs, Mn 2+ ion and cGAMP could be directly delivered into the cytoplasm of monocyte and induced lymph homing.…”

Section: Introductionmentioning

confidence: 99%

Cytosolic Delivery of Thiolated Mn‐cGAMP Nanovaccine to Enhance the Antitumor Immune Responses

Chen

Tong

Zheng

et al. 2021

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As a stimulator of interferon gene (STING), cyclic dinucleotide activates a broad cellular immune response for anti‐cancer immunotherapy (CIT). However, the inherent of instability of 2′ 3′‐cyclic‐GMP‐AMP (cGAMP) with poor cellular targeting, rapid clearance, and inefficient transport to the cytoplasm seriously hinders cGAMP potency. Here, a thiolated and Mn2+ coordinated cyclic dinucleotide nanovaccine (termed as Mn‐cGAMP NVs) to enable direct cytosolic co‐delivery of cGAMP and Mn2+ to potentiate the antitumor immune response is presented. In the NVs, the fixation cGAMP with Mn2+ ions not only improve its stability, but also potentiate the activation of STING. Meanwhile, the presence of polysulfides on the NVs surface allowed direct cytosolic delivery while avoiding degradation. In this way, the production of cytokines for activating T cells immunity is greatly elevated, which in turn suppressed the primary and distal tumors growth through long‐term immune memory and led to long‐term survival of poorly immunogenic B16F10 melanoma mice. Moreover, by further combining with anti‐PD‐L1 monoclonal antibody, synergistic T cells antitumor immune response is elicited. This work offers a promising strategy to enhance the potency of cGAMP, holding a considerable potential for CIT applications.

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Section: Introductionmentioning

confidence: 99%

Cytosolic Delivery of Thiolated Mn‐cGAMP Nanovaccine to Enhance the Antitumor Immune Responses

Chen

Tong

Zheng

et al. 2021

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“…However, it can quickly release DOX and SM in the weakly acidic environment of the tumor once it reaches the tumor tissue, exerting anti-tumor and anti-inflammatory activities. The nanodrug can realize the controllable release of DOX and SM with the help of the pH gradient between the systemic circulation and the tumor microenvironment [ 73 ]. The relationship between inflammation and tumor is mutual.…”

Section: Discussionmentioning

confidence: 99%

Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

et al. 2021

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Background Non-Hodgkin’s lymphoma (NHL) is a malignant disease of lymphoid tissue. At present, chemotherapy is still the main method for the treatment of NHL. R-CHOP can significantly improve the survival rate of patients. Unfortunately, DOX is the main cytotoxic drug in R-CHOP and it can lead to adverse reactions. Therefore, it is particularly important to uncover new treatment options for NHL. Results In this study, a novel anti-tumor nanoparticle complex Nm@MSNs-DOX/SM was designed and constructed in this study. Mesoporous silica nanoparticles (MSNs) loaded with Doxorubicin (DOX) and anti-inflammatory drugs Shanzhiside methylester (SM) were used as the core of nanoparticles. Neutrophil membrane (Nm) can be coated with multiple nanonuclei as a shell. DOX combined with SM can enhance the anti-tumor effect, and induce apoptosis of lymphoma cells and inhibit the expression of inflammatory factors related to tumorigenesis depending on the regulation of Bcl-2 family-mediated mitochondrial pathways, such as TNF-α and IL-1β. Consequently, the tumor microenvironment (TME) was reshaped, and the anti-tumor effect of DOX was amplified. Besides, Nm has good biocompatibility and can enhance the EPR effect of Nm@MSNs-DOX/SM and increase the effect of active targeting tumors. Conclusions This suggests that the Nm-modified drug delivery system Nm@MSNs-DOX/SM is a promising targeted chemotherapy and anti-inflammatory therapy nanocomplex, and may be employed as a specific and efficient anti-Lymphoma therapy.

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“…Reproduced with permission. [ 79 ] Copyright 2020, American Chemical Society. D) PD‐L1‐leuckocyte‐labeled iron oxide NP with TGF‐ b induces ferroptosis‐mediated ICD, thus modulating tumor microenvironments with tumor‐suppressive mode.…”

Section: Biomaterial‐based Immunogenic Cell Death (Icd) Inductionmentioning

confidence: 99%

Harnessing Innate Immunity Using Biomaterials for Cancer Immunotherapy

et al. 2021

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The discovery of immune checkpoint blockade has revolutionized the field of immuno‐oncology and established the foundation for developing various new therapies that can surpass conventional cancer treatments. Most recent immunotherapeutic strategies have focused on adaptive immune responses by targeting T cell‐activating pathways, genetic engineering of T cells with chimeric antigen receptors, or bispecific antibodies. Despite the unprecedented clinical success, these T cell‐based treatments have only benefited a small proportion of patients. Thus, the need for the next generation of cancer immunotherapy is driven by identifying novel therapeutic molecules or new immunoengineered cells. To maximize the therapeutic potency via innate immunogenicity, the convergence of innate immunity‐based therapy and biomaterials is required to yield an efficient index in clinical trials. This review highlights how biomaterials can efficiently reprogram and recruit innate immune cells in tumors and ultimately initiate activation of T cell immunity against advanced cancers. Moreover, the design and specific biomaterials that improve innate immune cells’ targeting ability to selectively activate immunogenicity with minimal adverse effects are discussed.

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Manganese-Based Nanoactivator Optimizes Cancer Immunotherapy via Enhancing Innate Immunity

Cited by 215 publications

References 50 publications

Cytosolic Delivery of Thiolated Mn‐cGAMP Nanovaccine to Enhance the Antitumor Immune Responses

Cytosolic Delivery of Thiolated Mn‐cGAMP Nanovaccine to Enhance the Antitumor Immune Responses

Biomimetic nanotherapy: core–shell structured nanocomplexes based on the neutrophil membrane for targeted therapy of lymphoma

Harnessing Innate Immunity Using Biomaterials for Cancer Immunotherapy

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