An extracellular pH-driven targeted multifunctional manganese arsenite delivery system for tumor imaging and therapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Arsenic trioxide (ATO) shows efficacy in acute promyelocytic leukemia (APL) but has limited use in solid tumors due to poor biocompatibility and toxicity.
• Developing targeted drug delivery systems is crucial for overcoming ATO's limitations in solid tumor treatment.

Purpose of the Study:

• To develop a multifunctional drug delivery system (DDS) based on ATO, modified with pH-low insertion peptide (pHLIP), for targeted solid tumor therapy.
• To investigate the controlled release, targeting ability, and theranostic potential of the novel DDS in vitro and in vivo.

Main Methods:

• Fabrication of a pH-low insertion peptide (pHLIP) modified, silica-coated arsenic trioxide (ATO) and manganese ion (Mn2+) loaded nanoparticle system (MnAs@SiO2-pHLIP).
• Evaluation of the DDS's targeting efficiency in acidic tumor microenvironments and controlled ATO release.
• Assessment of in vitro and in vivo anticancer efficacy, reduced toxicity, and magnetic resonance imaging (MRI) monitoring capabilities.

Main Results:

• MnAs@SiO2-pHLIP demonstrated efficient targeting of acidic tumor microenvironments and enhanced intracellular accumulation.
• The DDS exhibited controlled release of ATO in response to acidic conditions, promoting cancer cell apoptosis.
• In vitro and in vivo studies showed improved anticancer efficacy and reduced toxicity compared to free ATO, with MRI capability for real-time monitoring.

Conclusions:

• The developed MnAs@SiO2-pHLIP system offers a promising platform for targeted arsenic trioxide delivery in solid tumors.
• This multifunctional DDS enhances therapeutic efficacy, minimizes toxicity, and enables theranostic applications through MRI monitoring.
• The findings suggest significant potential for MnAs@SiO2-pHLIP in advancing cancer management strategies.