Tumor-microenvironment controlled nanomicelles with AIE property for boosting cancer therapy and apoptosis monitoring

Biomaterials. 2019 Jan:188:96-106. doi: 10.1016/j.biomaterials.2018.10.003. Epub 2018 Oct 9.

Abstract

Mild acidity matrix, rich blood vessels and special biomarkers constitute the primary tumor microenvironment. Nanoparticles could change their physicochemical characteristics by functionalizing a series of moieties which is responsive towards pH or specific markers. So precise regulation of nanocarrier-based drug delivery systems by the tumor microenvironment has showed great potential for theranostics. Herein, we developed a smart nano delivery system STD-NM, showing tumor microenvironment responsive targeting, efficient drug delivery and precise evaluation of therapeutic effect in vivo. STD-NM kept in 'stealth' state in normal environment while 'activated' in the tumor acidic environment, which could show stability in blood circulation while deeply penetrate into tumor tissues. Additionally, STD-NM was designed with aggregation-induced emission (AIE) characteristic, of which the fluorescence 'switch on' when apoptosis taken place. Gene analysis by RNA-seq also confirmed a superior therapeutic effect of drug loaded STD-NM treatment. We envisioned the well-designed smart nano materials for drug delivery could open a new avenue in precisely tumor imaging and specific cancer therapeutics.

Keywords: Drug delivery; Gene analysis; In vivo bioimaging; Microenvironment regulated; Smart materials; VEGFR2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis / drug effects*
  • Delayed-Action Preparations / chemistry*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems
  • Drug Liberation
  • Female
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Neoplasms / drug therapy
  • Tumor Microenvironment* / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Micelles
  • Doxorubicin