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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.
Abstract:
Therapeutic efficacy of nanoparticle-drug formulations for cancer applications is significantly impacted by the extent of intra-tumoral accumulation and tumor tissue penetration. We advanced the application of surface plasmon resonance to examine interfacial properties of various clinical and emerging nanoparticles related to tumor tissue penetration. We observed that amine-terminated or positively-charged dendrimers and liposomes bound strongly to tumor extracellular matrix (ECM) proteins, whereas hydroxyl/carboxyl-terminated dendrimers and PEGylated/neutrally-charged liposomes did not bind. In addition, poly(lactic-co-glycolic acid) (PLGA) nanoparticles formulated with cholic acid or F127 surfactants bound strongly to tumor ECM proteins, whereas nanoparticles formulated with poly(vinyl alcohol) did not bind. Unexpectedly, following blood serum incubation, this binding increased and particle transport in ex vivo tumor tissues reduced markedly. Finally, we characterized the protein corona on PLGA nanoparticles using quantitative proteomics. Through these studies, we identified valuable criteria for particle surface characteristics that are likely to mediate their tissue binding and tumor penetration.
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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