Tumor pH-triggered PEG detachable nanoparticles for TLR7/8 agonist delivery to improve cancer immunotherapy

Apr 15, 2025Biomaterials science

Nanoparticles that release immune-boosting drugs in acidic tumors to improve cancer treatment

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Abstract

R848-loaded mesoporous silica nanoparticles (R848@MSN-bi-PEG) enhance immune responses by promoting antigen-presenting cell (APC) function in acidic tumor environments.

R848@MSN-bi-PEG facilitates the uptake of the drug by APCs and the release of R848 in acidic conditions.
The treatment promotes the maturation of dendritic cells and the repolarization of macrophages to a pro-inflammatory state.
The study suggests an enhancement of anti-tumor immunity through modulation of the immunosuppressive tumor microenvironment.

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Antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs) are key players in modulating the immune responses of cytotoxic T lymphocytes (CTLs). Resiquimod (R848), a toll-like receptor (TLR) agonist, has demonstrated the capacity to enhance APC function and reprogram the phenotype of macrophages; however, the unfavorableperformance constrains its therapeutic potential. Here, we developed R848-loaded mesoporous silica nanoparticles (denoted as R848@MSN-bi-PEG) with pH-responsive surface polyethylene glycol (PEG) detachment to effectively modulate APCs. The acidic tumor pH triggered PEG detachment when R848@MSN-bi-PEG accumulated at the tumor site, thereby promoting APC uptake and R848 release, which facilitated DCs maturation and macrophage repolarization to a pro-inflammatory phenotype. Theantitumor study indicated that R848@MSN-bi-PEG led to potent anti-tumor immunity by modulating the immunosuppressive tumor microenvironment. This approach offers a novel strategy to improve the effectiveness of cancer immunotherapy. in vivo in vivo

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Tumor pH-triggered PEG detachable nanoparticles for TLR7/8 agonist delivery to improve cancer immunotherapy

Abstract

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