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PEG-grafted arsenic trioxide-loaded mesoporous silica nanoparticles endowed with pH-triggered delivery for liver cancer therapy. | LitMetric

AI Article Synopsis

  • Liver cancer (LC) has a poor prognosis and limited treatment options, prompting the exploration of new therapies like Arsenic trioxide (ATO), which has shown effectiveness but suffers from toxicity and poor drug delivery.
  • A new pH-responsive nanoplatform, PEG-MSN@ATO, was developed to enhance ATO's delivery specifically to tumor sites, reducing side effects and improving treatment outcomes by effectively regulating immune responses in the tumor microenvironment.
  • PEG-MSN@ATO was found to promote apoptosis, inhibit tumor growth and metastasis, and activate antitumor immunity, marking it as a promising approach for increased efficacy and reduced toxicity in LC treatment.

Article Abstract

Liver cancer (LC), one of the most common malignant primary tumors, presents a poor prognosis, high morbidity rate, and poor clinical outcomes. Despite conventional treatments have been applied prior to the deterioration, their clinical benefits were still limited. Arsenic trioxide (ATO), a toxic Chinese medicine, has been proven to efficiently inhibit the growth of LC both and . However, its therapeutic effects are hindered by poor pharmacokinetics and dose-limited toxicity. In this study, we developed a pH-responsive nanoplatform (PEG-MSN@ATO) consisting of mesoporous silica nanoparticles (MSN) that were modified with amino groups, loaded with ATO, and grafted with PEG to achieve the pH-triggered release and regulate CD8 T cells and T cells in the tumor microenvironment (TME). PEG-MSN@ATO were characterized by uniform size, good loading efficiency, pH-responsive release features, decreased macrophage uptake, and enhanced dendritic cell activation . Furthermore, studies demonstrated that PEG-MSN@ATO enhanced the antitumor efficacy by inducing apoptosis and ROS production, inhibiting tumor cell proliferation and metastasis, and activating antitumor immunity within the TME. PEG-MSN@ATO also reduced the system toxicity of ATO by controlling the pH-trigger release in the tumor site. These results indicate that the PEG-MSN@ATO represents a promising drug delivery platform for reducing toxicity and enhancing the therapeutic efficacy of ATO against LC.

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Source
http://dx.doi.org/10.1039/d3bm00555kDOI Listing

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