Leveraging Surface Plasmon Resonance to Dissect the Interfacial Properties of Nanoparticles: Implications for Tissue

Aniket S Wadajkar1, Jimena G Dancy1, Christine P Carney2

  • 1Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD; Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD.

Insights

Nanoparticle surface properties critically affect tumor penetration for cancer therapy. Positively charged or certain functionalized nanoparticles bind to tumor matrix proteins, hindering drug delivery and accumulation.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapeutics

Background:

  • Therapeutic efficacy of nanoparticle-drug formulations for cancer is limited by tumor penetration.
  • Understanding nanoparticle-tumor interactions is crucial for optimizing drug delivery.

Purpose of the Study:

  • To investigate how nanoparticle surface characteristics influence tumor tissue penetration.
  • To identify criteria for designing nanoparticles with improved tumor accumulation.

Main Methods:

  • Surface plasmon resonance used to assess nanoparticle-extracellular matrix (ECM) protein binding.
  • Evaluation of various nanoparticle types including dendrimers and liposomes.
  • Analysis of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations.
  • Quantitative proteomics to characterize protein corona formation.

Main Results:

  • Amine-terminated/positively-charged dendrimers and liposomes showed strong binding to tumor ECM proteins.
  • Hydroxyl/carboxyl-terminated dendrimers and PEGylated/neutral liposomes did not bind.
  • Certain PLGA nanoparticle formulations (cholic acid, F127) bound strongly to ECM, unlike poly(vinyl alcohol) formulations.
  • Serum incubation increased ECM binding and reduced ex vivo tumor tissue transport.

Conclusions:

  • Nanoparticle surface charge and functionalization significantly impact binding to tumor ECM proteins.
  • Strong ECM binding, especially after serum incubation, impedes nanoparticle penetration into tumor tissues.
  • Surface characteristics can be optimized to enhance nanoparticle tumor accumulation and therapeutic delivery.

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