Remotely Phototriggered, Transferrin-Targeted Polymeric Nanoparticles for the Treatment of Breast Cancer

Abstract

Triple Negative Breast Cancer (TNBC) has the worst prognosis amongst all sub-types of breast cancer. Currently no targeted treatment has been approved for TNBC. The goal of this study was to design a remotely triggered, targeted therapy for TNBC using polymeric nanoparticles and light. Active targeting of TNBC was achieved by conjugating the nanoparticles to a peptide (hTf) that binds to the transferrin receptor, which is overexpressed in TNBC. Photodynamic Therapy (PDT) was explored for TNBC treatment by remotely triggering benzoporphyrin derivative monoacid (BPD), a photosensitizer, using near infrared light. In this study, we investigated the use of actively targeting polymeric nanoparticles for PDT against TNBC using in vitro imaging and cytotoxicity studies. Fluorescence imaging confirmed that the BPD loaded nanoparticles showed greater fluorescence in TNBC cells compared to free BPD, but more importantly actively targeted nanoparticles displayed stronger fluorescence compared to passively targeted nanoparticles. Moreover, fluorescence imaging following competition with empty targeted nanoparticles validated the specificity of the targeted nanoparticles for TNBC cells. The PDT killing results were in line with the fluorescence imaging results, where actively targeting nanoparticles exhibited the highest phototriggered cytotoxicity in TNBC cells, making them an attractive nanoplatform for TNBC treatment.

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