Stimuli-responsive NO-generating nanoparticles for enhanced EPR effect and intratumoral accumulation of doxorubicin
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초록
내용
Targeted drug delivery and controlled drug release remain challenging. To address this challenge, we synthesized intracellular nitric oxide-generating nanoparticles (NO-NPs) for tumor site-specific generation of vasodilator NO to enhance NP accumulation in tumor tissue, i.e., improve their enhanced permeability and retention (EPR) effect. These NPs are self-assembled from amphiphilic copolymers of poly(ethylene glycol) and nitrated dextran, which possesses inherent NO-releasing properties in the reductive intracellular microenvironment. After systemic administration of NO-NPs, we quantitatively appraised the increased tumor blood flow and enhanced vascular permeability than that achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated substantial therapeutic efficacy over the control groups with improved intratumoral DOX accumulation. Overall, we anticipate NO-NPs being an EPR enhancer to achieve a better anticancer therapeutic efficiency.