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Updated: May 6, 2026

Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
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Idasanutlin-ionizable lipid nanocomplex for enhanced solubility, stability, and anticancer activity in p53 sensitive

Bhoomi Dholariya1, Akanksha Patel1, Rhema Khairnar1

  • 1College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11432, USA.

Colloids and Surfaces. B, Biointerfaces
|August 23, 2025
PubMed

Insights

This study developed a novel Idasanutlin loaded lipid Nanocomplex (IDLIN) to improve treatment for non-small cell lung cancer (NSCLC). IDLIN effectively delivered Idasanutlin, restoring p53 activity and showing significant anti-cancer effects in NSCLC models.

Area of Science:

  • Nanotechnology
  • Oncology
  • Drug Delivery

Background:

  • Lung cancer remains a leading cause of cancer mortality globally, often linked to p53 tumor suppressor gene dysfunction.
  • Idasanutlin (IDA) is an MDM2 inhibitor that can restore p53 activity in wild-type p53 cancers, but its clinical application is limited by poor solubility and stability.

Purpose of the Study:

  • To develop a novel Idasanutlin-loaded lipid Nanocomplex (IDLIN) to enhance solubility, stability, and loading efficiency of IDA.
  • To evaluate the therapeutic potential of IDLIN in non-small cell lung cancer (NSCLC) models.

Main Methods:

  • Formulation of IDLIN using a self-nanoemulsifying drug delivery system (SNEDDS) with a hydrophobic ion-pairing agent (DLin-DMA).
  • Characterization of IDLIN's physical properties (size, PDI, zeta potential) at different pH values.
  • In vitro evaluation of IDLIN's anti-cancer activity in NSCLC cell lines (A549, H460, PC9) and 3D tumor spheroid models.
  • Assessment of IDLIN's in vivo tolerability (hemolysis) and mechanism of action (Western blot analysis for p53 and MDM2).

Main Results:

  • IDLIN demonstrated significantly improved physical stability and loading efficiency compared to IDA alone.
  • IDLIN exhibited potent anti-cancer activity in NSCLC cell lines, inhibiting colony formation and tumor growth in 3D models.
  • Western blot analysis confirmed p53 and MDM2 upregulation in IDLIN-treated cells, indicating restored p53 pathway activity.
  • IDLIN showed good tolerability for intravenous administration with negligible hemolysis.

Conclusions:

  • IDLIN represents a promising nanoformulation for Idasanutlin delivery, enhancing its therapeutic potential in NSCLC.
  • The developed nano-delivery system effectively overcomes IDA's limitations, offering a viable strategy for NSCLC treatment.
Keywords:
DLin-DMAHydrophobic ion-pairing complexIdasanutlinMDM2 inhibitorNon-small cell lung cancerP53

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