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

Abstract

Triple-negative breast cancer (TNBC) has the worst prognosis among all subtypes 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.

Functional Polymer Nanocarriers for Photodynamic Therapy

“…Animal experiments on A549 tumor-bearing model in nude mice showed that the drug delivery system can achieve remarkable tumor inhibition rate while slight side effects in normal organs. Actively targeting polymeric nanoparticles conjugated with a peptide (hTf) ligand were used for against triple-negative breast cancer (TNBC) [111]. The hTf can specifically bind to the transferrin receptor and promote internalization of the nanocarrier.…”

Review: Organic nanoparticle based active targeting for photodynamic therapy treatment of breast cancer cells

“…Within PDT studies on MDA-MB-231 TNBC cells using a 690 nm laser more cytotoxicity was noted in ANP treatments when compared to free BPD PS treatments at a concentration of 100 nM. Furthermore, PDT experiments using higher concentrations of ANP, noted a significant 95% cell death for targeted and passively targeted NPs (PLGA-PEG-BPD or PNP) which confirmed that the encapsulation of BPD into ANP or PNP had great advantages over BPD treatments alone [89].…”

“…Within another study the PDT treatment of TNBC using MDA-MB-231 cells was performed with a transferrin-targeted polymeric NPs [89]. PLGA-PEGmethoxy and PLGA-PEG-maleimide (blend polymer) NPs were used combined with a benzoporphyrin derivative monoacid (BPD) PS and hTf peptides to actively target TNBC transferrin receptors and called ANP.…”

Liposomes Aid Curcumin's Combat with Cancer in a Breast Tumor Model

“…Monodispersity in nanoparticles is necessary to avoid causing an immune response [76][77][78]. The negative zeta potential of both PL and AL indicates that they have better systemic stability, and are less likely to cause immunogenicity in vivo [74,79,80]. Nanoparticles which are close to 100 nm can cross the blood-brain barrier and evade the reticuloendothelial system, resulting in prolonged circulation time, thus making smaller liposomes even more attractive as a biocompatible drug delivery system [5,81].…”