pH-sensitive and folic acid-targeted MPEG-PHIS/FA-PEG-VE mixed micelles for the delivery of PTX-VE and their antitumor activity

Abstract

The aim of this study was to simultaneously introduce pH sensitivity and folic acid (FA) targeting into a micelle system to achieve quick drug release and to enhance its accumulation in tumor cells. Paclitaxel-(+)-α-tocopherol (PTX-VE)-loaded mixed micelles (PHIS/FA/PM) fabricated by poly(ethylene glycol) methyl ether-poly(histidine) (MPEG-PHIS) and folic acid-poly(ethylene glycol)-(+)-α-tocopherol (FA-PEG-VE) were characterized by dynamic light scattering and transmission electron microscopy (TEM). The mixed micelles had a spherical morphology with an average diameter of 137.0±6.70 nm and a zeta potential of −48.7±4.25 mV. The drug encapsulation and loading efficiencies were 91.06%±2.45% and 5.28%±0.30%, respectively. The pH sensitivity was confirmed by changes in particle size, critical micelle concentration, and transmittance as a function of pH. MTT assay showed that PHIS/FA/PM had higher cytotoxicity at pH 6.0 than at pH 7.4, and lower cytotoxicity in the presence of free FA. Confocal laser scanning microscope images demonstrated a time-dependent and FA-inhibited cellular uptake. In vivo imaging confirmed that the mixed micelles targeted accumulation at tumor sites and the tumor inhibition rate was 85.97%. The results proved that the mixed micelle system fabricated by MPEG-PHIS and FA-PEG-VE is a promising approach to improve antitumor efficacy.

Doxorubicin‑loaded dual‑functional hyaluronic acid nanoparticles: Preparation, characterization and antitumor efficacy in�vitro and in�vivo

“…Meanwhile, compared with the free DOX group, the DOX/GHH nanoparticle group showed higher antitumor efficacy. A possible explanation is that GA-receptor-mediated endocytosis inhibits P-glycoprotein-mediated drug efflux, resulting in its high antitumor efficacy (38,39). The in vivo antitumor efficacy of the DOX/GHH nanoparticles was investigated against H22 tumor-bearing mice.…”

Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery

“…These micelles presented high cytotoxicity and destabilisation in the acid environment of endosomes, which caused the release of paclitaxel. The rate of sarcoma tumour inhibition in female Kunming mice was 85.97% [ 19 ]. Recent studies evaluated the drug delivery system encapsulated with doxorubicin, which was composed of Bletilla striata polysaccharide modified with stearic acid (SA) and targeted with folate (FA-BSP-SA).…”

“…Compared to surfactant micelles, block copolymer-based micelles are characterized by higher stability and larger versatility for controlling micellar structure and functionality by choices of polymer composition, architecture, molecular weight and monomer chemistry [ 17 ]. Moreover, surface modification enables enhanced tissue penetration and targeting properties [ 18 , 19 , 20 ].…”

pH-Responsive Zwitterionic Copolymer DHA–PBLG–PCB for Targeted Drug Delivery: A Computer Simulation Study

“…Over the past few decades, the incidence of cancer has been increasing year by year; however, the current state of cancer therapy is still far from satisfactory . Until now, the commonly used treatments for cancer include surgery, radiotherapy, chemotherapy, and gene therapy . Among them, chemotherapy drugs have poor water solubility, chemical instability, low permeability, serious toxicity, and side effects. , The design of novel drug delivery systems (DDS) is emergent.…”

“…Among these stimuli, pH responsiveness is a commonly used strategy to control self-assembly and disassemble for various applications, especially for targeted drug release. It is generally known that the pH in most cancer tissues and cells can reach as low as 4.5 (e.g., endosomes); , however, the physiological pH of blood and normal tissues is ∼7.4. Because of the different pH values in various microenvironments of issues, pH-responsive micelles are attractive to realize the targeted drug delivery.…”