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Overcoming drug-resistant lung cancer by paclitaxel loaded tetrahedral DNA nanostructures

X Xie1, X Shao1, W Ma1

  • 1State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, P. R. China. yunfenglin@scu.edu.cn.

Nanoscale
|February 28, 2018
PubMed

Insights

Tetrahedral DNA nanostructures loaded with paclitaxel (PTX/TDNs) effectively kill lung cancer cells, including drug-resistant types. This novel nanodelivery system overcomes paclitaxel resistance by inhibiting P-glycoprotein and inducing apoptosis.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Paclitaxel (PTX) is a vital chemotherapy drug, but its efficacy is hindered by multidrug resistance (MDR).
  • Tetrahedral DNA nanostructures (TDNs) present a promising platform for drug delivery applications.
  • Developing effective strategies to overcome PTX resistance is crucial for improving cancer treatment outcomes.

Purpose of the Study:

  • To evaluate the efficacy of PTX-loaded TDNs (PTX/TDNs) in overcoming paclitaxel resistance in non-small cell lung cancer (NSCLC).
  • To investigate the mechanisms by which PTX/TDNs overcome drug resistance.
  • To assess the potential of PTX/TDNs as a nanodelivery system for treating PTX-resistant NSCLC.

Main Methods:

  • Preparation and characterization of PTX/TDNs.
  • Cytotoxicity assessment of PTX/TDNs and free PTX on NSCLC (A549) and PTX-resistant (A549/T) cell lines using CCK-8 assay.
  • Analysis of mdr1 gene and P-glycoprotein (P-gp) expression in A549/T cells.
  • Investigation of apoptosis induction by PTX/TDNs.

Main Results:

  • PTX/TDNs demonstrated significant cytotoxicity against both sensitive (A549) and resistant (A549/T) NSCLC cells.
  • The drug resistance of A549/T cells was effectively overcome by PTX/TDNs.
  • TDNs were found to downregulate the expression of mdr1 gene and P-gp, indicating their role as P-gp inhibitors.
  • PTX/TDNs induced apoptosis in cancer cells.

Conclusions:

  • PTX/TDNs exhibit potent anti-cancer activity and overcome paclitaxel resistance in NSCLC.
  • TDNs function as P-gp inhibitors, contributing to the reversal of multidrug resistance.
  • PTX/TDNs hold significant potential as an effective nanodelivery system for treating paclitaxel-resistant NSCLC.

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