Self-Targeted, Shape-Assisted, and Controlled-Release Self-Delivery Nanodrug for Synergistic Targeting/Anticancer Effect of Cytoplasm and Nucleus of Cancer Cells

ACS Appl Mater Interfaces. 2015 Nov 25;7(46):25553-9. doi: 10.1021/acsami.5b07348. Epub 2015 Nov 10.

Abstract

We constructed 10-hydroxycamptothecin (CPT) "nanodrugs" with functionalization of lipid-PEG-methotrexate (MTX) to prepare high-drug-loaded, and sustained/controlled-release MTX-PEG-CPT nanorods (NRs), in which MTX drug itself can serve as a specific "targeting ligand". The self-targeted nanodrug can codeliver both CPT and MTX drugs with distinct anticancer mechanisms. Furthermore, MTX-PEG-CPT NRs significantly reduced burst release, improved blood circulation and tumor accumulation, enhanced cellular uptake, and synergistically increased anticancer effect against tumor cells compared with MTX-PEG-CPT nanospheres (NSs) and either both free drugs or individual free drug. Therefore, the synergistic targeting/therapeuticy nano-multi-drug codelivery assisted by shape design may advantageously offer a promising new strategy for nanomedicine.

Keywords: DSPE-PEG-MTX; nanodrug; self-targeted drug delivery; sustain/controlled drug release; synergistic anticancer activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • Cell Survival / drug effects
  • Delayed-Action Preparations
  • Drug Synergism
  • Endocytosis / drug effects
  • Fluorescence
  • Methotrexate / pharmacology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanospheres / chemistry
  • Nanospheres / ultrastructure
  • Nanotubes / chemistry*
  • Nanotubes / ultrastructure
  • Particle Size
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • 10-hydroxycamptothecin
  • Camptothecin
  • Methotrexate