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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
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Tumor specific delivery and therapy by double-targeted nanostructured lipid carriers with anti-VEGFR-2 antibody

Donghua Liu1, Fengxi Liu, Zhihong Liu

  • 1School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Ji'nan 250012, China.

Molecular Pharmaceutics
|September 20, 2011
PubMed

Insights

This study developed antibody-modified nanostructured lipid carriers (tNLC) to target vascular endothelial growth factor receptors (VEGFRs) on tumors. The tNLC effectively delivered docetaxel (DTX), showing superior antitumor efficacy and tumor vascular targeting in vivo.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Vascular endothelial growth factor receptors (VEGFRs) are overexpressed on tumor cells and neovasculature, presenting a target for dual-action cancer therapy.
  • Targeted drug delivery systems can enhance chemotherapeutic efficacy and reduce side effects.

Purpose of the Study:

  • To develop a VEGFR-mediated drug delivery system using antibody-modified docetaxel-loaded nanostructured lipid carriers (tNLC).
  • To evaluate the in vitro and in vivo efficacy of tNLC for targeting VEGFR-overexpressing tumor cells and neovasculature.

Main Methods:

  • Antibody-modified docetaxel-loaded targeted nanostructured lipid carriers (tNLC) were prepared using DSPE-PEG-NH(2) as a linker.
  • Evaluated tNLC's particle size, encapsulation efficiency, drug loading, and ligand coupling efficiency.
  • Assessed cellular cytotoxicity, cellular uptake, in vivo therapeutic effect, and biodistribution in a murine tumor model.

Main Results:

  • tNLC exhibited a particle size of ~168 nm with high encapsulation efficiency (>95%) and drug loading (5.55%).
  • tNLC demonstrated superior cytotoxicity against tumor cell lines compared to Duopafei and non-targeted NLC (nNLC).
  • In vivo studies showed enhanced antitumor efficacy, better tolerance, and increased drug accumulation in tumor and vasculature for tNLC.

Conclusions:

  • The developed tNLC effectively targets VEGFR-2, delivering docetaxel to both tumor cells and tumor vasculature.
  • tNLC shows significant potential as a targeted therapy for inhibiting tumor growth by exploiting VEGFR overexpression.

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