Dopamine Delivery via pH-Sensitive Nanoparticles for Tumor Blood Vessel Normalization and an Improved Effect of Cancer Chemotherapeutic Drugs

Mohammad Taleb, Yanping Ding, Bin Wang, Na Yang, Xuexiang Han, Chong Du, Yingqiu Qi, Yinlong Zhang, Zeinab Farhadi Sabet, Hamideh Rezvani Alanagh, Ayeesha Mujeeb, Khosro Khajeh, Guangjun Nie

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Tumor blood vessels have been reported to be abnormal in both structure and function compared with those in normal tissues, leading to a hostile microenvironment and inadequate antitumor drug delivery. Dopamine, a chemical messenger, is proven to inhibit angiogenesis and improve tumor vessel normalization. Here, a mesoporous silicon nanoparticle (MSN) is constructed that is responsive to the weakly acidic pH of the tumor extracellular matrix for steady delivery and tumor-localized release of dopamine. Then MSNs are functionalized with amine conjugated phenylboronicacid molecules, and dopamine is loaded by reacting with phenylboronic acid. In a weakly acidic environment, MSNs intelligently release dopamine due to the hydrolysis of boronic-ester bond between dopamine and phenylboronic acid, resulting in an evident inhibition of vascular endothelial cell migration and tubule formation. It is shown that loading of dopamine into the functional MSNs significantly prolong the circulatory half-life of this small molecule. After intravenous injection to tumor bearing mice, this nanoformulation induce tumor blood vessel normalization, thereby improving the antitumor chemotherapeutic efficacy of doxorubicin. This study demonstrates that the pH-responsive MSN offers great potential for delivery of dopamine in vivo and the normalization of tumor vessels by dopamine can provide an auxiliary treatment for cancer chemotherapeutic drugs.

Original languageEnglish (US)
Article number1900283
JournalAdvanced Healthcare Materials
Volume8
Issue number18
DOIs
StatePublished - Sep 1 2019

Keywords

  • dopamine
  • mesoporous silicon nanoparticles
  • pH responsiveness
  • tumor vessel normalization

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

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