Folate‐Conjugated and Dual Stimuli‐Responsive Mixed Micelles Loading Indocyanine Green for Photothermal and Photodynamic Therapy

Abstract

A folic acid targeted mixed micelle system based on co-assembly of poly(ε-caprolactone)-b-poly(methoxytri(ethylene glycol) methacrylate-co-N-(2-methacrylamido)ethyl folatic amide) and poly(ε-caprolactone)-b-poly(diethylene glycol monomethyl ether methacrylate) is developed to encapsulate indocyanine green (ICG) for photothermal therapy and photodynamic therapy. In this study, the use of folic acid is not only for specific cancer cell recognition, but also in virtue of the carboxylic acid on folic acid to regulate the pH-dependent thermal phase transition of polymeric micelles for controlled drug release. The prepared ICG-loaded mixed micelles possess several superior properties such as a preferable thermoresponsive behavior, excellent storage stability, and good local hyperthermia and reactive oxygen species generation under near-infrared (NIR) irradiation. The photototoxicity induced by the ICG-loaded micelles has efficiently suppressed the growth of HeLa cells (folate receptor positive cells) under NIR irradiation compared to that of HT-29, which has low folate receptor expression. Hence, this new type of mixed micelles with excellent features could be a promising delivery system for controlled drug release, effective cancer cell targeting, and photoactivated therapy.

Functional Polymer Nanocarriers for Photodynamic Therapy

“…In this way, active targeting can guarantee the specific accumulation of nanoparticles in tumor tissues and enhance the specificity of PDT. The targeting moieties, such as peptides [66,80,81], aptamers [82], and proteins have been applied to target tumor vasculature [83,84], tumor cells [85], and subcellular organelles [45,46].…”

“…Folic acid is an essential reactant in the synthesis process of nucleotide bases and folate receptors are overexpressed on the surfaces of the malignant cells. The stable, inexpensive, easily conjugated characteristics make folic acid a promise candidate ligands for targeted cancer therapy [85,104,105,106,107]. Cheng et al developed a charge-switchable nanocapsules for FA-targeted chemo/photodynamic therapy [79].…”

Folate-Targeted Curcumin-Encapsulated Micellar Nanosystem for Chemotherapy and Curcumin-Mediated Photodynamic Therapy

“…In this study, a series of folate-conjugated poly(2-methacryloyl-oxyethyl phosphorylcholine)- b - poly(ε-caprolactone) (FA-PMPC- b -PCL, FPM) was prepared via ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), and click reaction according to our previous synthetic procedures and published protocols [ 22 , 23 , 24 ]. The synthetic route is shown in Scheme 1 and the polymer characterizations are given in the Supplementary Material (Table S1 and Figures S1–S3 ).…”

Physically stimulus-responsive nanoparticles for therapy and diagnosis

“…Another system that applies PTT and PDT combination is a mixed micelle based on the co -assembly of PCL- b -poly(methoxytri(ethylene glycol) methacrylate- co - N -(2-methacrylamido)ethyl folate amide) (PCL- b -P(TEGMA- co -NMFA) and PCL- b -poly(diethyleneglycolmonomethylether methacrylate) (PCL- b -PDEGMA), which is targeted with folate receptor and encapsulated ICG. Upon NIR irradiation, the toxicity induction by the micelle@ICG has effectively inhibited the growth of HeLa cells ( Chien et al, 2018 ).…”