Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl2 Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation

Liu, Xinghan; Xu, Yujun; Yin, Liangyu; Hou, Yinglong; Zhao, Shuli

doi:10.2147/ijn.s318363

Cited by 18 publications

(10 citation statements)

References 63 publications

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“…Moreover, in patients with advanced metastatic solid tumors who failed in standard anticancer treatments such as chemotherapies, radiotherapy, and immunotherapies, Mn 2+ administration exhibits a notably improved therapeutic efficacy with 45.5% objective response and 90.9% disease control ( Lv et al., 2020 ). Significantly, similar enhanced antitumor effects by Mn 2+ -promoted cGAS–STING activation in various antitumor immunotherapies have been reported ( Hou et al., 2020 ; Chen et al., 2021 ; Gao et al., 2021 ; Li et al., 2021a ; Liu et al., 2021 ; Song et al., 2021 ; Sun et al., 2021a ; Wang et al., 2021a ; Yang et al., 2021 ; Yi et al., 2021 ). Considering the component simplicity and steadiness of Mn 2+ , Mn 2+ treatment or combined antitumor therapies including immunotherapies may have promising clinical potential.…”

Section: Applications Of Mn 2+ -Activated Cgas–sti...supporting

confidence: 74%

Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation

Zhao

Jiang

2022

Journal of Molecular Cell Biology

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The cGAS-STING pathway, comprising the DNA sensor cyclic GMP-AMP synthetase (cGAS), the second messenger cyclic GMP-AMP (cGAMP), and the endoplasmic reticulum (ER) adaptor protein stimulator of interferon genes (STING), detects cytoplasmic double-stranded DNA (dsDNA) to trigger type I-interferon responses for host defense against pathogens. Previous studies defined a model for the allosteric activation of cGAS by DNA-binding, but recent work reveals other layers of mechanisms to regulate cGAS activation such as the phase condensation and metal ions, especially the discovery of Mn2+ as a cGAS activator. Activation of the 2’3’-cGAMP sensor STING requires translocating from ER to the Golgi apparatus. The sulfated glycosaminoglycans (sGAGs) at the Golgi are found to be the second STING ligands promoting STING oligomerization and activation in addition to 2’3’-cGAMP, while surpassed levels of 2’3’-cGAMP induce ER-located STING to form a highly organized ER membranous condensate named STING phase-separator to restrain STING activation. Here, we summarize recent advances in the regulation of cGAS-STING activation and their implications in physiological or pathological conditions, particularly focusing on the emerging complexity of the regulation.

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Section: Applications Of Mn 2+ -Activated Cgas–sti...supporting

confidence: 74%

Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation

Zhao

Jiang

2022

Journal of Molecular Cell Biology

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“…NPs can suppress tumor growth through targeted immunomodulation. Studies have demonstrated NPs altering macrophage polarization towards an M1-like phenotype and increasing CH8+ T cell density [ 24 , 25 ]. Among them, one study utilized nanosized membrane vesicles, known as extracellular vesicles (EVs), which were isolated and purified from the ginseng root, known for their anticancer properties [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…GDNP treatment significantly suppressed melanoma growth in tumor-bearing mice by increasing the presence of M1 macrophages detected in tumor tissue [ 26 ]. A separate study found that chitosan-poly(acrylic acid) NPs (CS-PAA), loaded with R848 and MnCl 2 (R-M@CS-PAA NPs), can also exert an anti-tumor effect by promoting the M1 phenotype [ 24 ]. R848 is a toll-like receptor (TLR)7/8 agonist that is known to effectively drive the M1 polarization of tumor-associated macrophages [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…A separate study found that chitosan-poly(acrylic acid) NPs (CS-PAA), loaded with R848 and MnCl 2 (R-M@CS-PAA NPs), can also exert an anti-tumor effect by promoting the M1 phenotype [ 24 ]. R848 is a toll-like receptor (TLR)7/8 agonist that is known to effectively drive the M1 polarization of tumor-associated macrophages [ 24 ]. Administration of R848 alone, however, can cause adverse side effects.…”

Section: Resultsmentioning

confidence: 99%

“…Administration of R848 alone, however, can cause adverse side effects. Mn 2+ can also enhance the activation of CD8+ T cells and natural killer cells [ 24 ]. R-M@CS-PAA NPs enhanced the polarization of macrophages into the M1 phenotype, and they inhibited the proliferation of B16F10 cells [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

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et al. 2023

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Nanoparticles have shown marked promise as both antineoplastic agents and drug carriers. Despite strides made in immunomodulation, low success rates and toxicity remain limitations within the clinical oncology setting. In the present review, we assess advances in drug delivery nanoparticles, for systemic and topical use, in skin cancer treatment. A systematic review of controlled trials, meta-analyses, and Cochrane review articles was conducted. Eligibility criteria included: (1) a primary focus on nanoparticle utility for skin cancer; (2) available metrics on prevention and treatment outcomes; (3) detailed subject population; (4) English language; (5) archived as full-text journal articles. A total of 43 articles were selected for review. Qualitative analysis revealed that nanoscale systems demonstrate significant antineoplastic and anti-metastasis properties: increased drug bioavailability, reduced toxicity, enhanced permeability and retention effect, as well as tumor growth inhibition, among others. Nanoformulations for skin cancers have largely lagged behind those tested in other cancers–several of which have commercialized formulae. However, emerging evidence has indicated a powerful role for these carriers in targeting primary and metastatic skin cancers.

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Photothermal Propelling and Pyroelectric Potential‐Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy

Wei

Liu

et al. 2023

Adv Healthcare Materials

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Cancer phototherapy experiences limitations in tissue diffusion and cell internalization of phototherapeutic agents and dose‐dependent side effects. Herein, Janus pyroelectric nanoparticles (NPs) are designed to generate self‐powered motion and built‐in electric fields to overcome the delivery barriers. Polydopamine (PDA) layers are partially coated on tetragonal BaTiO3 (tBT) NPs to prepare Janus tBT@PDA, and Au NPs are deposited on the PDA caps to obtain Janus tBT@PDA‐Au NPs. Near‐infrared (NIR) illumination of tBT@PDA‐Au builds in situ pyroelectric potentials on NPs, which selectively affect the membrane potential of tumor cells rather than normal cells to enhance tumor cell internalization and produce reactive oxygen species (ROS) for pyroelectric dynamic therapy (PEDT). The asymmetric photothermal effect of the Janus NPs creates thermophoretic force to propel NP motion, which enhances tumor diffusion and cellular uptake of NPs and boosts cytotoxicity and intracellular ROS levels. The inoculation of Au NPs increases the photothermal effect, exhibits larger motion velocities, produces higher pyroelectric potentials, and elevates cellular uptake rates, resulting in significant induction of tumor cell apoptosis, suppression of tumor growth, and extension of animal survival. Thus, the concise design of tBT@PDA‐Au/NIR treatment has achieved thermophoretic motion‐promoted tissue diffusion, built‐in electric field‐enhanced cell internalization, and photothermal/PEDT‐synergized antitumor efficacy.

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Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl2 Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation

Cited by 18 publications

References 63 publications

Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation

Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation

Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review

Photothermal Propelling and Pyroelectric Potential‐Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy

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