AIE Supramolecular Assembly with FRET Effect for Visualizing Drug Delivery

Abstract

Here, we constructed a nanostructured pH/redox dual-responsive supramolecular drug carrier with both aggregation-induced emission (AIE) and Forster resonance energy transfer (FRET) effects, which enabled selective drug release and monitoring drug delivery and release processes. Taking the hyperbranched polyamide amine (H-PAMAM) with intrinsic AIE effects as the core, poly­(ethylene glycol) (PEG) was bridged on its periphery by dithiodipropionic acid. Then, through the host–guest interaction of PEG and α-cyclodextrin, the supramolecular nanoparticles with AIE effects were constructed to load the anticancer drug doxorubicin (DOX). The supramolecular assembly has sufficiently large DOX loading due to the abundant cavities formed by branched structures. The hyperbranched core H-PAMAM has strong fluorescence, and the dynamic track of drug carriers and the dynamic drug release process can be monitored by the AIE and FRET effects between H-PAMAM and DOX, respectively. Furthermore, the introduction of disulfide bonds and the pH sensitivity of H-PAMAM enable the achievement of rapid selective release of loaded DOX at the tumor while remaining stable under normal physiological conditions. In vitro cytotoxicity indicates that the drug-loaded supramolecular assembly has a good therapeutic effect on cancer. In addition, the H-PAMAM core is different from the traditional AIE functional group, which has no conjugated structure, such as a benzene ring, thereby providing better biocompatibility. This technology will have broad applications as a new drug delivery system.

Binding interactions and FRET between bovine serum albumin and various phenothiazine-/anthracene-based dyes: a structure–property relationship

“…15,16 C5-PTZCN, C5-PTZDCA, and ANTDCA are the compounds that were newly synthesized. Their structures were veried by FT-IR, LCMS (Liquid Chromatography Mass Spectrometry)/HRMS (High-Resolution Mass Spectrometry), and 1 H and 13 C NMR data (see ESI; pages (3)(4)(5)(6) and Fig. (S11-S16) †). PTZ, ANT, ANTA, and BSA were procured from Alfa-Aesar and Sigma Aldrich.…”

“…3 Since the discovery of the FRET, researchers have been actively utilizing this potential non-radiative tool to unveil numerous facts related to the eld of supramolecular materials and biomedical research and development. 4,5 There is a rapid growth in the invention of donor-acceptor combinations for the FRET applications. However, constructing an appropriate donor-acceptor pair for the FRET is still a challenge because it needs to meet primary inuencing criteria such as distance, spectral overlap, and dipole orientation between donors and acceptors.…”

Aggregation‐enhanced theranostics: AIE sparkles in biomedical field

“…AIE-active supramolecular nanomaterials for drug/gene delivery and bioimaging have been fabricated, with which the drug delivery process can be monitored and the therapeutic functions can be regulated upon the external stimuli. [150] Besides, theranostic prodrugs and hybrid materials based on the hostguest interactions of CDs and AIEgens can realize the multifunctional and synergistic therapies with the guidance of FLI, which can satisfied the different clinical demands. [151,152] Recently, Ding et al reported the supramolecular AIE nanomaterials based on the host-guest interaction of α-CDs and PEG, which exhibited high performance for imaging-guided orthotopic pancreatic cancer therapy.…”

Nanomaterials with Supramolecular Assembly Based on AIE Luminogens for Theranostic Applications

“…Wang et al reported a pH-and redox-responsive supramolecular drug nanocarrier with both AIE and FRET effects. [96] DOX-loaded nanocarriers can be constructed by hyperbranched polyamide amine (H-PAMAM), PEG, and α-CD via hostguest interaction. The strong fluorescence of hyperbranched core H-PAMAM enabled the supramolecular nanocarrier to monitor the dynamic drug release process.…”