Designing high specificity anti-cancer nanocarriers by exploiting non-equilibrium effects

ORAL

Abstract

Although targeting of cancer cells using drug-delivering nanocarriers holds promise for improving therapeutic agent specificity, the strategy of maximizing ligand affinity for receptors overexpressed on cancer cells is suboptimal. To determine design principles that maximize nanocarrier specificity for cancer cells, we studied a generalized kinetics-based theoretical model of nanocarriers with one or more ligands that specifically bind these overexpressed receptors. We show that kinetics inherent to the system play an important role in determining specificity and can in fact be exploited to attain orders of magnitude improvement in specificity. In contrast to the current trend of therapeutic design, we show that these specificity increases can generally be achieved by a combination of low rates of endocytosis and nanocarriers with multiple low-affinity ligands. These results are broadly robust across endocytosis mechanisms and drug-delivery protocols, suggesting the need for a paradigm shift in receptor- targeted drug-delivery design.

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Authors

  • Konstantinos Tsekouras

    Cal Poly

  • Nilgun Sungar

    Department of Physics and Astronomy, University of California, Irvine, University of California, Irvine, California State University, Fresno, Physics Department, University of California, Santa Cruz, CA, 95064, Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Upton, New York 11973, Seogang University, Pohang University of Science \& Technology, UC Santa Cruz, Trinity College, Hartford, Los Alamos National Laboratory, University of Connecticut, Storrs, CSU Long Beach, Physics/Hokkaido University, Japan, Physics/University of California, San Deigo, Physics/California State University, Fresno, CSU Stanislaus, University of California, Santa Barbara, Instituted of Astronomy, University of Cambridge, UK, Max-Planck Institute for Radio Astronomy, Bonn, Germany, Institute of Astronomy, University of Cambridge, UK, California Polytechnic State University, San Luis Obispo, SpaceX, Northrop-Grumman, Cal Poly San Luis Obispo, Department of Physics, University of California at Davis, Davis 95616, United States Department of Agriculture-Agriculture Research Service, Chemistry/California State University Fresno, Physics/California State University Fresno, University of California Santa Barbara, University of California Merced, UC Merced, Stanford University, New Economic School, California Polytechnic State University San Luis Obispo, Indiana University - Purdue University Indianapolis, California Polytechnic State University, San Luis Obispo, Chair of the Physics Department

  • Nilgun Sungar

    Department of Physics and Astronomy, University of California, Irvine, University of California, Irvine, California State University, Fresno, Physics Department, University of California, Santa Cruz, CA, 95064, Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Upton, New York 11973, Seogang University, Pohang University of Science \& Technology, UC Santa Cruz, Trinity College, Hartford, Los Alamos National Laboratory, University of Connecticut, Storrs, CSU Long Beach, Physics/Hokkaido University, Japan, Physics/University of California, San Deigo, Physics/California State University, Fresno, CSU Stanislaus, University of California, Santa Barbara, Instituted of Astronomy, University of Cambridge, UK, Max-Planck Institute for Radio Astronomy, Bonn, Germany, Institute of Astronomy, University of Cambridge, UK, California Polytechnic State University, San Luis Obispo, SpaceX, Northrop-Grumman, Cal Poly San Luis Obispo, Department of Physics, University of California at Davis, Davis 95616, United States Department of Agriculture-Agriculture Research Service, Chemistry/California State University Fresno, Physics/California State University Fresno, University of California Santa Barbara, University of California Merced, UC Merced, Stanford University, New Economic School, California Polytechnic State University San Luis Obispo, Indiana University - Purdue University Indianapolis, California Polytechnic State University, San Luis Obispo, Chair of the Physics Department

  • Nilgun Sungar

    Department of Physics and Astronomy, University of California, Irvine, University of California, Irvine, California State University, Fresno, Physics Department, University of California, Santa Cruz, CA, 95064, Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Upton, New York 11973, Seogang University, Pohang University of Science \& Technology, UC Santa Cruz, Trinity College, Hartford, Los Alamos National Laboratory, University of Connecticut, Storrs, CSU Long Beach, Physics/Hokkaido University, Japan, Physics/University of California, San Deigo, Physics/California State University, Fresno, CSU Stanislaus, University of California, Santa Barbara, Instituted of Astronomy, University of Cambridge, UK, Max-Planck Institute for Radio Astronomy, Bonn, Germany, Institute of Astronomy, University of Cambridge, UK, California Polytechnic State University, San Luis Obispo, SpaceX, Northrop-Grumman, Cal Poly San Luis Obispo, Department of Physics, University of California at Davis, Davis 95616, United States Department of Agriculture-Agriculture Research Service, Chemistry/California State University Fresno, Physics/California State University Fresno, University of California Santa Barbara, University of California Merced, UC Merced, Stanford University, New Economic School, California Polytechnic State University San Luis Obispo, Indiana University - Purdue University Indianapolis, California Polytechnic State University, San Luis Obispo, Chair of the Physics Department

  • Nilgun Sungar

    Department of Physics and Astronomy, University of California, Irvine, University of California, Irvine, California State University, Fresno, Physics Department, University of California, Santa Cruz, CA, 95064, Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Upton, New York 11973, Seogang University, Pohang University of Science \& Technology, UC Santa Cruz, Trinity College, Hartford, Los Alamos National Laboratory, University of Connecticut, Storrs, CSU Long Beach, Physics/Hokkaido University, Japan, Physics/University of California, San Deigo, Physics/California State University, Fresno, CSU Stanislaus, University of California, Santa Barbara, Instituted of Astronomy, University of Cambridge, UK, Max-Planck Institute for Radio Astronomy, Bonn, Germany, Institute of Astronomy, University of Cambridge, UK, California Polytechnic State University, San Luis Obispo, SpaceX, Northrop-Grumman, Cal Poly San Luis Obispo, Department of Physics, University of California at Davis, Davis 95616, United States Department of Agriculture-Agriculture Research Service, Chemistry/California State University Fresno, Physics/California State University Fresno, University of California Santa Barbara, University of California Merced, UC Merced, Stanford University, New Economic School, California Polytechnic State University San Luis Obispo, Indiana University - Purdue University Indianapolis, California Polytechnic State University, San Luis Obispo, Chair of the Physics Department