Cross‐Linking of Thiolated Paclitaxel–Oligo(p‐phenylene vinylene) Conjugates Aggregates inside Tumor Cells Leads to “Chemical Locks” That Increase Drug Efficacy

Abstract

How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and related taxoid anticancer drugs is a major challenge for improving cure rates. An oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX), which enhances drug efficacy and reverses resistance is thus designed. The mechanism involves diffusion of OPV-S-PTX into the cell, where π-π interactions lead to aggregation. Cross-linking of the aggregates via oxidation of thiol groups is favored in tumor cells because of the higher reactive oxygen species (ROS) concentration. Cross-linked aggregates "chemically lock" the multichromophore particle for a more persistent effect. The IC of OPV-S-PTX for tumor cell line A549 is reduced down to 0.33 × 10 m from that observed for PTX itself (41 × 10 m). Enhanced efficacy by OPV-S-PTX is proposed to proceed via acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice experiments reveal suppression of tumor growth upon OPV-S-PTX treatment. Altogether, these results show that the internal cross-linking of OPV-S-PTX through ROS provides a means to discriminate between tumor and healthy cells and the formation of the chemically locked particles enhances drug efficacy and helps in reducing resistance.

Poly(N-isopropylacrylamide)-Based Thermoresponsive Composite Hydrogels for Biomedical Applications

“…With the development of modern biomedicine, targeted therapy and sustained drug release have become very attractive strategies due to their advantages in reducing cytotoxicity, shortening drug cycling period, improving curative effect and so on [16,[80][81][82][83][84][85][86]. PNIPAM hydrogel is a promising material for drug delivery that can encapsulate drugs easily and give a temperature-dependent drug release in a slow and linear profile [9,[87][88][89].…”

Fluorescent and Biocompatible Ruthenium‐Coordinated Oligo(p‐phenylenevinylene) Nanocatalysts for Transfer Hydrogenation in the Mitochondria of Living Cells

“…As oligo( p‐ phenylenevinylene) (OPV) and its derivatives are easy to assemble in water through π–π stacking and hydrophobic interaction, it will contribute to amplifying the function of functional groups through improving local concentration . Also due to their good biocompatibility, OPV derivatives have been widely applied in biological field such as imaging and cancer therapy …”

“…As oligo(p-phenylenevinylene) (OPV) and its derivatives are easy to assemble in water through p-p stacking and hydrophobic interaction, it will contribute to amplifying the function of functionalg roups through improving local concentration. [14] Also due to their good biocompatibility,O PV derivatives have been widely applied in biological fields uch as imaging and cancert herapy. [15][16] In view of this, it is exciting to know whetheri ti spossible to enhance the catalytic activity inside living cells by linking am etal actives ite to an OPV backbone.…”

Tumour microenvironment-responsive semiconducting polymer-based self-assembling nanotheranostics

“…25,26 Semiconducting organic molecule based nanomaterials have been employed as promising carriers for biomedical applications owing to numerous advantages over other nanomaterials. [27][28][29] Perylene diimide (PDI) has attracted great interest as a scaffold material for encapsulation or covalent conjugation of therapeutic agents, aiming to achieve robust stability, excellent photothermal efficiency, and good biocompatibility for cancer theranostics. 30,31 In addition, the coordination chemistry between metal and polyphenols has been exploited for various biomedical applications.…”