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Peptide-Functionalized Nanoparticles-Encapsulated Cyclin-Dependent Kinases Inhibitor Seliciclib in Transferrin

Guan Zhen He1, Wen Jen Lin1,2

  • 1School of Pharmacy, College of Medicine, National Taiwan University, Taipei 10050, Taiwan.

Nanomaterials (Basel, Switzerland)
|April 3, 2021
PubMed

Insights

Targeted nanoparticles loaded with seliciclib show enhanced cancer cell uptake and efficacy. T7 peptide decoration improves delivery to transferrin receptor-overexpressing cancer cells, increasing drug sensitivity.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapeutics

Background:

  • Seliciclib is a cyclin-dependent kinases (CDKs) inhibitor with potential in cancer therapy.
  • Cancer cells often overexpress transferrin receptors (TfRs), presenting a target for drug delivery.
  • Targeted delivery systems can enhance nanoparticle internalization and drug efficacy.

Purpose of the Study:

  • To develop T7 peptide-decorated nanoparticles (NPs) for targeted delivery of seliciclib.
  • To evaluate the cellular uptake and anti-cancer efficacy of these targeted NPs.
  • To assess the drug sensitivity of cancer cells treated with seliciclib-loaded NPs.

Main Methods:

  • Synthesized poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-maleimide (PLGA-PEG-maleimide) copolymer.
  • Prepared seliciclib-encapsulated NPs and decorated them with T7 peptide.
  • Assessed cellular uptake in cancer cell lines with varying TfR expression (MDA-MB-231, SKOV-3, U87-MG).
  • Determined the inhibitory concentration 50 (IC50) values for free and encapsulated seliciclib.

Main Results:

  • T7 peptide-modified NPs demonstrated superior cellular uptake in TfR-high expressing cancer cells.
  • Uptake efficiency followed the order: MDA-MB-231 > SKOV-3 > U87-MG.
  • SKOV-3 and U87-MG cells showed increased sensitivity to seliciclib encapsulated in T7-decorated NPs.
  • Encapsulation led to lower IC50 values compared to free seliciclib.

Conclusions:

  • T7 peptide-mediated targeting enhances nanoparticle delivery to TfR-overexpressing cancer cells.
  • Seliciclib-loaded, T7-decorated NPs exhibit improved anti-cancer efficacy.
  • This targeted nanodelivery system holds promise for seliciclib-based cancer therapy.
Keywords:
T7 peptideTfR-overexpressed cancer cellsnanoparticlesseliciclib

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