Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

Yi Cao ¹Xiaojiao Ge ²Yuanyuan Wei ²Lulu He ²Aiguo Wu ²Juan Li²

扫码查看

作者信息

1. Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology,Zhejiang International Cooperation Base of Biomedical Materials Technology and Application,Chinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and Devices,Ningbo Cixi Institute of Biomedical Engineering,Zhejiang Engineering Research Center for Biomedical Materials,Ningbo Institute of Materials Technology and Engineering,Chinese Academy of Sciences,Ningbo 315201,China;University of Chinese Academy of Sciences,Beijing
2. Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology,Zhejiang International Cooperation Base of Biomedical Materials Technology and Application,Chinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and Devices,Ningbo Cixi Institute of Biomedical Engineering,Zhejiang Engineering Research Center for Biomedical Materials,Ningbo Institute of Materials Technology and Engineering,Chinese Academy of Sciences,Ningbo 315201,China;Advanced Energy Science and Technology Guangdong L
折叠

Abstract

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs.Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors.However,active regulation of calcium level through signal transduction of bioactive substances has not been reported yet.In this study,novel neuropeptide-doxorubicin conju-gates(NP-DOX)with lysosome-specific acid response were described for neuropeptide Y1 receptor(Y1R)-overexpressed triple-negative breast cancer.The delivery mechanism of NP-DOX was clarified that diverse pathways were involved,including intracellular and intercellular transport.Importantly,up-regulation of Y1R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells.In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y1R-mediated calcium deposition,compared with free DOX.This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great po-tential for further applications in tumor chemotherapy.

Key words

Neuropeptide-drug conjugate/Tumor penetration/Calcium deposition/Tumor inhibition/Triple-negative breast cancer

引用本文复制引用

基金项目

Key Research and Development Pro-gram of Zhejiang Province(2020C03110)

国家自然科学基金(T2222021)

国家自然科学基金(32011530115)

国家自然科学基金(32025021)

Science and Technology Bureau of Ningbo City(2020Z094)

Science and Technology Bureau of Ningbo City(2021Z072)

Excellent Member of Youth Innovation Promotion Association Foundation of CAS(Y2021079)

出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

参考文献量1

段落导航