Cationic Polymeric Nanoparticle Delivering CCR2 siRNA to Inflammatory Monocytes for Tumor Microenvironment Modification and Cancer Therapy

Shen, Song; Zhang, Yue; Chen, Kai-Ge; Luo, Ying-Li; Wang, Jun

doi:10.1021/acs.molpharmaceut.7b00997

Cited by 71 publications

(41 citation statements)

References 50 publications

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“…These NPs led to a decrease in macrophage number in tumors, reduced tumor size, IL-10, and TGF-β, while an increase in CD8 + T cells [ 165 ]. A similar result was observed for siCCR2-NPs intravenously injected in orthotopic models of breast cancer [ 166 ]. These NPs may act on the monocyte precursors of TAMs, as the CCL2/CCR2 axis is the main responsible of monocyte recruitment towards tumors [ 3 ].…”

Section: Genetic and Epigenetic Intervention To Reprogram Tamssupporting

confidence: 84%

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Belgiovine

Digifico

Anfray

et al. 2020

JCM

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In the last decade, it has been well-established that tumor-infiltrating myeloid cells fuel not only the process of carcinogenesis through cancer-related inflammation mechanisms, but also tumor progression, invasion, and metastasis. In particular, tumor-associated macrophages (TAMs) are the most abundant leucocyte subset in many cancers and play a major role in the creation of a protective niche for tumor cells. Their ability to generate an immune-suppressive environment is crucial to escape the immune system and to allow the tumor to proliferate and metastasize to distant sites. Conventional therapies, including chemotherapy and radiotherapy, are often not able to limit cancer growth due to the presence of pro-tumoral TAMs; these are also responsible for the failure of novel immunotherapies based on immune-checkpoint inhibition. Several novel therapeutic strategies have been implemented to deplete TAMs; however, more recent approaches aim to use TAMs themselves as weapons to fight cancer. Exploiting their functional plasticity, the reprogramming of TAMs aims to convert immunosuppressive and pro-tumoral macrophages into immunostimulatory and anti-tumor cytotoxic effector cells. This shift eventually leads to the reconstitution of a reactive immune landscape able to destroy the tumor. In this review, we summarize the current knowledge on strategies able to reprogram TAMs with single as well as combination therapies.

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Section: Genetic and Epigenetic Intervention To Reprogram Tamssupporting

confidence: 84%

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Belgiovine

Digifico

Anfray

et al. 2020

JCM

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“…also used cationic nanoparticles to deliver CCR2 siRNA, which showed remarkable targeting to monocytes in the peripheral blood, bone marrow, and spleen. [ 32 ] This approach enabled efficient inhibition of monocyte recruitment and decreased TAM infiltration, resulting in remodeling of the immunosuppressive tumor microenvironment. Similarly, Qian et al.…”

Section: Engineering Macrophages For Cancer Immunotherapymentioning

confidence: 99%

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

et al. 2020

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was that most nanoparticles do not have a sufficiently long blood half-life and cannot realize deep penetration in tumor tissue. Thus, recent progress in the development of strategies for mimicking or modulating cells offers a highly attractive alternative to drug delivery. [10-17] As natural immune cells and antigenpresenting cells, macrophages [18] have a long blood half-life and can specifically bind to tumor tissue. Therefore, applying macrophages in chemical drug delivery would lead to a significant increase in drug accumulation in tumors. Since macrophages can engulf foreign particles in nature, they can directly phagocytose drugs and then deliver drugs to tumors. [19] Thus, live macrophages may serve as drug carriers. To further increase the tumor-targeting ability of macrophages, they can be engineered with targeting ligands. [20] In addition, learning from red blood cell (RBC) membrane coating technology, [21-23] a macrophage cell membrane coating was developed and it resulted in enhanced tumor uptake of drugs. On the other hand, macrophages play an important role in modulating the tumor immune microenvironment. M1 macrophages inhibit tumor growth, while M2 macrophages promote tumor growth. Inhibition of M2 macrophages and repolarization of M2 macrophages to M1 macrophages are common strategies to treat solid tumors. Furthermore, since these macrophages express SIRPα on their surface, their phagocytic activity against CD47-expressing tumor cells is significantly affected by the CD47-SIRPα pathway. Therefore, blocking the CD47-SIRPα pathway can further enhance the anti-tumor efficacy of macrophages. Herein, to elucidate the importance of macrophages in tumor therapy (Figure 1), we will first discuss the role of macrophages in cancer immunotherapy, including the inhibition, depletion, and repolarization of tumor-associated macrophages (TAMs) and the blocking of the CD47-SIRPα pathway to enhance phagocytosis in tumor therapy. Then, based on the tumor targeting of M1 macrophages, we will discuss the applications of macrophages, macrophage-derived exosomes, and macrophage-coated NPs for drug delivery. We will thus offer a comprehensive understanding of functionalizing macrophages for tumor therapy. Macrophages play an important role in cancer development and metastasis. Proinflammatory M1 macrophages can phagocytose tumor cells, while antiinflammatory M2 macrophages such as tumor-associated macrophages (TAMs) promote tumor growth and invasion. Modulating the tumor immune microenvironment through engineering macrophages is efficacious in tumor therapy. M1 macrophages target cancerous cells and, therefore, can be used as drug carriers for tumor therapy. Herein, the strategies to engineer macrophages for cancer immunotherapy, such as inhibition of macrophage recruitment, depletion of TAMs, reprograming of TAMs, and blocking of the CD47-SIRPα pathway, are discussed. Further, the recent advances in drug delivery using M1 macrophages, macrophage-derived exosomes, and macrophage-membrane-coated nanoparticles are ela...

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“…Peripheral monocytes, TAM predecessors, are recruited into the tumor lesions through the engagement of CSF1/ CSF1R [313] and CCL2/CCR2 [310]; hence, the blockade of these factors might potentially reduce the accumulation of TAMs in tumors, thereby overcoming the TAM-related immunosuppression and enhancing tumor-specific T cell responses. For example, Shen et al generated monocytetargeting cationic nanoparticles to deliver CCR2 siRNA for inhibiting the recruitment of Ly6C hi monocytes by blocking CCL2-CCR2 pathways [314,315]. Furthermore, Ramesh et al developed a CSF1R-and SHP2-inhibitor-loaded nanoparticle for reinforcing cytotoxic activity and phagocytosis of TAMs [316].…”

Section: Tam-targeting Treatmentsmentioning

confidence: 99%

Recent Advancements in Nanomedicine for ‘Cold’ Tumor Immunotherapy

Chen¹,

Sun²

2021

Nano-Micro Lett.

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Although current anticancer immunotherapies using immune checkpoint inhibitors (ICIs) have been reported with a high clinical success rate, numerous patients still bear ‘cold’ tumors with insufficient T cell infiltration and low immunogenicity, responding poorly to ICI therapy. Considering the advancements in precision medicine, in-depth mechanism studies on the tumor immune microenvironment (TIME) among cold tumors are required to improve the treatment for these patients. Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy, activates immune function, modulates the TIME, and has been applied in combination with other anticancer therapeutic strategies. This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies, as well as a brief talk about the feasibility of clinical translation.

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Cationic Polymeric Nanoparticle Delivering CCR2 siRNA to Inflammatory Monocytes for Tumor Microenvironment Modification and Cancer Therapy

Cited by 71 publications

References 50 publications

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Targeting Tumor-Associated Macrophages in Anti-Cancer Therapies: Convincing the Traitors to Do the Right Thing

Engineering Macrophages for Cancer Immunotherapy and Drug Delivery

Recent Advancements in Nanomedicine for ‘Cold’ Tumor Immunotherapy

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