Design of Dual-Targeted pH-Sensitive Hybrid Polymer Micelles for Breast Cancer Treatment: Three Birds with One Stone

Abstract

Breast cancer has a high prevalence in the world and creates a substantial socio-economic impact. Polymer micelles used as nano-sized polymer therapeutics have shown great advantages in treating breast cancer. Here, we aim to develop a dual-targeted pH-sensitive hybrid polymer (HPPF) micelles for improving the stability, controlled-release ability and targeting ability of the breast cancer treatment options. The HPPF micelles were constructed using the hyaluronic acid modified polyhistidine (HA-PHis) and folic acid modified Plannick (PF127-FA), which were characterized via 1H NMR. The optimized mixing ratio (HA-PHis:PF127-FA) was 8:2 according to the change of particle size and zeta potential. The stability of HPPF micelles were enhanced with the higher zeta potential and lower critical micelle concentration compared with HA-PHis and PF127-FA. The drug release percents significantly increased from 45% to 90% with the decrease in pH, which illustrated that HPPF micelles were pH-sensitive owing to the protonation of PHis. The cytotoxicity, in vitro cellular uptake and in vivo fluorescence imaging experiments showed that HPPF micelles had the highest targeting ability utilizing FA and HA, compared with HA-PHis and PF127-FA. Thus, this study constructs an innovative nano-scaled drug delivery system, which provides a new strategy for the treatment of breast cancer.

Package delivered: folate receptor-mediated transporters in cancer therapy and diagnosis

“…Very recently, Yang and Liu et al designed dual-targeted pH-sensitive polymeric micelles constructed using the hyaluronic acid-modified poly-histidine (HA-PHis) and FA-conjugated F127. 110 Interestingly, the effect of FA-conjugated DTX-loaded micelles on the cell survival rate (IC 50 ) in HepG2 and MCF-7 cells was reported about 2.5 and 10 μg mL −1 , respectively.…”

Multi‐responsive co‐assembled polyurethane nanomicelles as anticancer drug delivery carriers

“…At present, chemotherapy is an important method to treat cancer, but its clinical application is restricted due to poor water solubility, fast metabolism, and serious systemic toxicity of chemotherapy drugs 3–8 . Amphiphilic polymers can self‐assemble in water to form nanomicelles, which can encapsulate insoluble drugs to improve their solubility, prolong their circulation time in the blood and then deliver them into tumor cells through the enhanced permeability and retention (EPR) effect 9–14 . Therefore, nanomicelles from amphiphilic polymers as drug carriers have been attracted much attentions during the past several decades 15–18 …”