Issue 37, 2023

[12]aneN3-modified camptothecin and PEGylated AIEgens co-assembly into core–shell nanoparticles with ROS/NTR dual-response for enhanced cancer therapy

Abstract

A novel dual-responsive nanoparticle (NP) system was aimed to be developed for the co-delivery of camptothecin (CPT) and plasmid encoding TNF-related apoptosis-inducing ligand (pTRAIL) DNA in cancer therapy. The combination of the prodrug CPT and the nucleic acid condensing di-(triazole-[12]aneN3) unit with 4-nitrobenzyl ester through alkyl chains resulted in three nitroreductase (NTR) responsive amphiphiles, CNN1–CNN3 (with 5, 8, and 11 carbon chains, respectively). Among them, CNN2 was the most effective in inhibiting the proliferation of HeLa cells in the presence of fusogenic lipid DOPE. The NPs composed of CNN2, pDNA, and DOPE were further co-assembled with ROS-responsive thioketal-linked amphiphilic polymer (TTP) to afford the core–shell NPs (CNN2-DT/pDNA) with an average size of 118 nm, which exhibited high drug-loading capacity, excellent serum tolerance, and good biocompatibility. In the presence of ROS, NTR, and NADH, the core–shell NPs were decomposed, leading to the efficient release of 80% CPT and abundant pDNA. The self-assembly and delivery process of CNN2-DT NPs and DNA were clearly observed through the AIE fluorescent imaging. In vitro and in vivo results demonstrated that the CNN2-DT/pTRAIL NPs synergistically promoted 68% apoptosis of tumor cells and inhibited tumor growth with negligible toxic side effects. This study showed that the combination of prodrug and nucleic acid through dual-responsive core–shell NPs provide a spatially and temporally-controlled strategy for cancer therapy.

Graphical abstract: [12]aneN3-modified camptothecin and PEGylated AIEgens co-assembly into core–shell nanoparticles with ROS/NTR dual-response for enhanced cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
05 ጁን 2023
Accepted
29 ኦገስ 2023
First published
07 ሴፕቴ 2023

J. Mater. Chem. B, 2023,11, 8943-8955

[12]aneN3-modified camptothecin and PEGylated AIEgens co-assembly into core–shell nanoparticles with ROS/NTR dual-response for enhanced cancer therapy

X. Sun, Y. Liang, Y. Gao, X. Zhang, R. Liu, Q. Tang, Z. Lu and Y. Liu, J. Mater. Chem. B, 2023, 11, 8943 DOI: 10.1039/D3TB01282D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements