Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles

Suping Li, Yinlong Zhang, Shih Hsin Ho, Bozhao Li, Meifang Wang, Xiongwei Deng, Na Yang, Guangna Liu, Zefang Lu, Junchao Xu, Quanwei Shi, Jing Yan Han, Lirong Zhang, Yan Wu, Yuliang Zhao, Guangjun Nie

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin–fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.

Original languageEnglish (US)
Pages (from-to)732-742
Number of pages11
JournalNature Biomedical Engineering
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2020

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Fingerprint Dive into the research topics of 'Combination of tumour-infarction therapy and chemotherapy via the co-delivery of doxorubicin and thrombin encapsulated in tumour-targeted nanoparticles'. Together they form a unique fingerprint.

Cite this