Acid‐sensitive reactive oxygen species triggered dual‐drug delivery systems for chemo‐photodynamic therapy to overcome multidrug resistance

Abstract

In clinical treatment, multidrug resistance (MDR) is one of the major obstacles resulting in the failure of chemotherapy. It is still a challenge to overcome MDR. Herein, we fabricated intelligent dextran-based dual-drug delivery systems histidine modified dextran conjugated doxorubicin/zinc porphyrin/paclitaxel (DHTD/Zn-TPP/PTX) via supramolecular metallo-coordination for synergistic chemo-photodynamic therapy to overcome cancer drug resistance. In this designed DHTD/Zn-TPP/PTX, one anticancer drug (doxorubicin, DOX) was conjugated on the dextran backbone through a reactive oxygen species sensitive linker and the other drug PTX was encapsulated into the acid responsive supramolecular micelles formed by the photosensitizer Zn-TPP and histidine grafted on dextran. DHTD/Zn-TPP/PTX with excellent stability could be effectively internalized by tumour cells. In the acidic tumour environment, the loaded PTX and Zn-TPP as photosensitizer could be released; moreover, when irradiated with light the conjugated DOX could be specifically released because the linker broke. As the obtained data indicate, DHTD/Zn-TPP/PTX exhibited not only an enhanced anticancer therapeutic effect but also significant growth inhibition for drug-resistant MCF-7/ADR cells to reverse MDR, having great potential for synergistic treatments of cancer to overcome MDR.

Micelles Based on Lysine, Histidine, or Arginine: Designing Structures for Enhanced Drug Delivery

“…The simplest way to develop micelles containing histidine is to attach hydrophobic histidine to hydrophilic macromolecules, such as hyaluronic acid ( Wu et al, 2016 ), dextran ( Yin et al, 2020 ), and auricularia auricular polysaccharide (AAP) ( Wang et al, 2017 ). In the above micelles, histidine is usually used as a micellar core.…”

Controlled Bioactive Delivery Using Degradable Electroactive Polymers

“…The first examples of degradable EAP-based DDSs were based on electroactive oligomers of aniline combined with nonelectroactive blocks, , and since that time, other examples have been reported in the literature incorporating electroactive oligomers (typically oligoanilines). , The literature precedent on the toxicity of oligoanilines ,, motivates the investigation of biomaterials incorporating other electroactive moieties, for example, oligopyrroles/porphyrins, which are being developed for a multitude of technical and medical applications. − …”