Abstract

Chemodynamic therapy (CDT) has been widely used in the treatment of many kinds of tumors, which can effectively induce tumor cell apoptosis by using produced reactive oxygen species (ROS). In this paper, ROS-sensitive multifunctional marine biomaterial natural polysaccharide nanoparticles were designed. Aggregation-induced emission (AIE) molecules tetraphenylethylene (TPE) labeled and caffeic acid (CA) modified fucoidan (FUC) amphiphilic carrier material (CA-FUC-TK-TPE, CFTT) was fabricated, in which the thioketal bond(TK) was used as the linkage arm between TPE and fucoidan chain, giving the CFTT material ROS sensitivity. In addition, amphiphilic carrier material (FUC-TK-VE, FTVE) composed of thioketal-linked vitamin E and fucoidan was synthesized. The mixed carrier material CFTT and FTVE self-assembled in water to form nanoparticles (CFTT – FTVE@PTX-Fe3+) loaded with PTX and Fe3+. The CDT effect was combined with the chemotherapeutic drug PTX to achieve tumor inhibition. In vitro cell studies have proved that CT/PTX nanoparticles have excellent cell permeability and tumor cytotoxicity. In vivo antitumor experiments confirmed effective antitumor activity and reduced side effects.

Highlights

  • Since 2001, a series of luminescent materials with aggregation-induced luminescence (AIE) properties have been developed[1,2,3]

  • The results showed that Fe3+ in CT/PTX nanoparticles could be used as Fenton reaction catalyst-like to produce reactive oxygen species (ROS)

  • We designed and constructed a type of novel ROS-responsive nanomedicine based on marine fucoidan by combining PTX chemotherapy and Chemodynamic therapy (CDT)

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Summary

Introduction

Since 2001, a series of luminescent materials with aggregation-induced luminescence (AIE) properties have been developed[1,2,3]. Compared with the aggregation-caused quenching effect (ACQ), aggregationinduced luminescent fluorophores (AIEgens) have almost no radiation in dilute solution, but have high radiation in the aggregated state due to limited intramolecular motion[4, 5]. High levels of ROS can cause oxidative damage to cellular biomolecules such as lipids, proteins, and nucleic acid molecules, leading to tumor cell death[10]. Chemodynamic therapy (CDT) is a new therapeutic strategy, which uses biochemical reactions (such as Fenton reaction and Fenton-like reaction) to produce ROS for the killing of tumor cells[11,12,13]. Iron-mediated Fenton reaction could convert hydrogen peroxide (H2O2) into highly cytotoxic hydroxyl radicals (OH)[14]

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