Fabrication of a Dual‐Stimuli‐Responsive Supramolecular Micelle from a Pillar[5]arene‐Based Supramolecular Diblock Copolymer for Photodynamic Therapy

Abstract

A pH and thermo dual‐responsive supramolecular diblock copolymer is constructed by host–guest recognition of pillar[5]arene and viologen salt. The host polymer, poly(N,N‐dimethylaminoethyl methacrylate) bearing pillar[5]arene as the terminal group (P[5]A‐PDMAEMA) is synthesized by atom transfer radical polymerization (ATRP). Guest polymer, ethyl viologen‐ended poly(N‐isopropylacrylamide) (EV‐PNIPAM) is prepared by reversible addition–fragmentation chain transfer polymerization. The supramolecular diblock copolymer can be self‐assembled into stable supramolecular nanoparticles in aqueous solution at 40 °C, which show excellent pH and thermo responsiveness. The nanoparticles are further applied in the encapsulation of photosensitizers (pyropheophorbide‐a, PhA) for photodynamic therapy (PDT). The dual‐responsive nanoparticles can efficiently release PhA in acidic environment at 25 °C. Based on the result of cell experiments, PhA‐loaded nanomicelles exhibit excellent PDT efficacy and low dark toxicity toward A549 cells. Thus, this supramolecular diblock copolymer enriches the methodology of constructing stimuli‐responsive drug carriers and presents a great potential in PDT.

Recent advances of stimuli-responsive viologen-based nanocomposites

“…Zhang, Cao, Xu, and coworkers prepared a supramolecular nanoparticles with dual response to pH and thermal stimulation using pillar [5]arene and viologen derivatives. 147 The nanoparticles encapsulating the photosensitizer (pyropheophorbide-a, PhA) could effectively release PhA in an acidic environment, achieving good PDT effect on A549 cells.…”

Pillararene-Based Supramolecular Polymers for Cancer Therapy

“…Xu, Cao, Zhang, and co-workers constructed a pH- and temperature-responsive supramolecular diblock copolymer for drug delivery, which was obtained by the host–guest recognition of pillar[5]arene and viologen salts ( Figure 10 I) [ 173 ]. The supramolecular diblock copolymer could self-assemble into supramolecular nanoparticles, which were used for the encapsulation of PSs (pyropheophorbide-a, PhA) for PDT.…”

Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

“…Second-generation PSs have a variety of functional groups including carboxyl, hydroxyl and amine groups in addition to their basic porphyrin structure, allowing hydrophobic modifications via chemical or physical approaches to form amphiphilic PS derivatives. The PS derivatives synthesized to be amphiphilic can form NPs with various nanostructures such as micelles [ 89 , 95 , 96 , 97 , 98 ], PS-drug conjugates [ 82 , 86 , 92 , 99 , 100 ], polymersomes [ 101 ], and nanogels [ 84 , 102 ] through self-assembly. According to the nanostructure, nanoparticles can be generally categorized into three types: 1) NPs with mixed hydrophilic and hydrophobic domains, 2) NPs with a core-shell structure, and 3) NPs with a double-layered capsule structure ( Figure 2 ).…”