Relaxin-encapsulated polymeric metformin nanoparticles remodel tumor immune microenvironment by reducing CAFs for efficient triple-negative breast cancer immunotherapy

Zhang, Hongyan; Chen, Liying; Zhao, Yue; Luo, Ningchao; Shi, Jingbin; Xu, Shujun; Ma, Lan; Wang, Menglin; Gu, Mancang; Mu, Chaofeng; Xiong, Yang

doi:10.1016/j.ajps.2023.100796

Cited by 12 publications

(8 citation statements)

References 62 publications

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“…The relaxin expression in 4T1 tumors reduced stromal deposition and diminished CAFs expression and the system showed 2.2-fold increase in cytotoxic T cell infiltration and decreased immunosuppressive cells infiltration. Depletion of CAFs along with blocking of PDL-1 receptors significantly improved anti-tumoral immunity, as was seen by the recruitment of CD8 + and CD4 + T-cells in 4T1 mouse tumor models (Zhang et al, 2023).…”

Section: Cmentioning

confidence: 80%

Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles

Towner,

Dissanayake,

Ahmed

2024

J Pharmacol Exp Ther

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Section: Cmentioning

confidence: 80%

Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles

Towner,

Dissanayake,

Ahmed

2024

J Pharmacol Exp Ther

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“…71 Polymeric metformin nanoparticles are highly positively charged polymer chain for effective delivery of genes, with the advantages of small molecular, excellent tolerability and low toxicity. 115 19 However, because CS is not water-soluble, it has limited biological applications. 128 The structure of CS with free -NH2 and −OH is amenable to chemical modifications that can improve the properties for application.…”

Section: The Biomaterials Science Of Tnbcmentioning

confidence: 99%

“…Zhang et al developed lipid poly(γ-glutamic acid)/polymeric metformin nanoparticles with a plasmid expressing relaxin. These nanoparticles increased T-cell infiltration within tumors and diminished the penetration of immunosuppressive cells in vivo . In the mouse model of TNBC, the nanosystem facilitated the reduction of fibrosis and the infiltration of CD8 + T cells.…”

Section: Reversal Of the Immunosuppressive Microenvironmentmentioning

confidence: 99%

“…These nanoparticles increased T-cell infiltration within tumors and diminished the penetration of immunosuppressive cells in vivo . 115 In the mouse model of TNBC, the nanosystem facilitated the reduction of fibrosis and the infiltration of CD8 + T cells. This shifted the immunosuppressive environment to an immunostimulatory state, resulting in a considerable improvement in the tumor immune microenvironment and the effectiveness of anti-PD-L1 therapy.…”

Section: Reversal Of the Immunosuppressive Microenvironmentmentioning

confidence: 99%

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Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer

Wang,

Huang,

Chen

et al. 2024

ACS Biomater. Sci. Eng.

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Triple-negative breast cancer (TNBC) is an aggressive subtype with the worst prognosis and highest recurrence rates. The treatment choices are limited due to the scarcity of endocrine and HER2 targets, except for chemotherapy. However, the side effects of chemotherapy restrict its long-term usage. Immunotherapy shows potential as a promising therapeutic strategy, such as inducing immunogenic cell death, immune checkpoint therapy, and immune adjuvant therapy. Nanotechnology offers unique advantages in the field of immunotherapy, such as improved delivery and targeted release of immunotherapeutic agents and enhanced bioavailability of immunomodulators. As well as the potential for combination therapy synergistically enhanced by nanocarriers. Nanoparticles-based combined application of multiple immunotherapies is designed to take the tactics of enhancing immunogenicity and reversing immunosuppression. Moreover, the increasing abundance of biomedical materials holds more promise for the development of this field. This review summarizes the advances in the field of nanoparticle-mediated immunotherapy in terms of both immune strategies for treatment and the development of biomaterials and presents challenges and hopes for the future.

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“…188 Lipid poly-γglutamic acid (PGA)/PolyMet-pRLN nanoparticles (LPPR) can rapidly penetrate tumors and weaken the proliferation of CAFs, remodeling the TME, and decreasing the infiltration of immunosuppressive cells to achieve efficient breast cancer immunotherapy. 189 Tumor immunotherapy and radiotherapy are the best partners based on nanosystems governance. Radiotherapy has certain immunostimulatory effects, and the synergistic effect of the two is beneficial for tumor control.…”

Section: Nanoparticle-targeted Cafs Combined With Radiotherapy and Im...mentioning

confidence: 99%

Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer

Wang,

Xue,

Yuan

et al. 2024

IJN

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Currently, pancreatic cancer (PC) is one of the most lethal malignant tumors. PC is typically diagnosed at a late stage, exhibits a poor response to conventional treatment, and has a bleak prognosis. Unfortunately, PC's survival rate has not significantly improved since the 1960s. Cancer-associated fibroblasts (CAFs) are a key component of the pancreatic tumor microenvironment (TME). They play a vital role in maintaining the extracellular matrix and facilitating the intricate communication between cancer cells and infiltrated immune cells. Exploring therapeutic approaches targeting CAFs may reverse the current landscape of PC therapy. In recent years, nano-drug delivery systems have evolved rapidly and have been able to accurately target and precisely release drugs with little or no toxicity to the whole body. In this review, we will comprehensively discuss the origin, heterogeneity, potential targets, and recent advances in the nano-drug delivery system of CAFs in PC. We will also propose a novel integrated treatment regimen that utilizes a nano-drug delivery system to target CAFs in PC, combined with radiotherapy and immunotherapy. Additionally, we will address the challenges that this regimen currently faces.

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Relaxin-encapsulated polymeric metformin nanoparticles remodel tumor immune microenvironment by reducing CAFs for efficient triple-negative breast cancer immunotherapy

Cited by 12 publications

References 62 publications

Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles

Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles

Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer

Nano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer

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