Affiliation:
1. The Second Affiliated Hospital of Guangzhou Medical University School of Biomedical Engineering Guangzhou Medical University Guangzhou 511436 P. R. China
2. Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, The NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences and the Fifth Affiliated Hospital Guangzhou Medical University Guangzhou 511436 P. R. China
3. The Second Affiliated Hospital State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology Guangzhou Medical University Guangzhou 510260 P. R. China
Abstract
AbstractThe high heterogeneity of receptor expression and varied chemotherapeutic sensitivity seriously compromise the therapeutic outcome of triple‐negative breast cancer (TNBC)‐targeting nanodrugs. In this work, a TNBC‐targeting nanodrug (designated as CPU) equipped with self‐promoted targeting property through chemotherapeutic upregulation of CD47 is constructed, enabling synergistic chemo/photodynamic therapy. Specifically, the hydrophobic docetaxel (DOC), which can upregulate the expression of CD47 in TNBC cells, is loaded in the nanomicelles (designated as P‐Pep) assembled from a protoporphyrin IX (PPIX)‐labeled amphiphilic chimeric peptide of Fmoc‐K(PPIX)‐AWSATWSNYWRH, obtaining the ca. 196 nm CPU. Aided by the enhanced permeability and retention effect and guidance of CD47‐binding peptide sequence, CPU is verified to prefer to accumulate in CD47 overexpressed TNBC cells, which can recruit more CPU by upregulating CD47 expression post‐treatment of DOC. Both in vitro and in vivo results demonstrate the superior tumor targeting ability, which can extensively amplify chemotherapeutic and photodynamic therapeutic effects while evading obvious adverse effects. The self‐promoted targeting strategy will inspire the design of nanodrugs for the personalized therapy of tumors with high heterogeneity and resistance.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Basic and Applied Basic Research Foundation of Guangdong Province
Subject
Electrochemistry,Condensed Matter Physics,Biomaterials,Electronic, Optical and Magnetic Materials