Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 43, Pages 15344-15349Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1411499111
Keywords
nanomedicine; size effect; silica nanoparticle; mathematical model; drug delivery
Categories
Funding
- National Institutes of Health (NIH) Director's New Innovator Award Program [1DP2OD007246-01, 1R21CA152627]
- NIH National Cancer Institute Alliance for Nanotechnology in Cancer Midwest Cancer Nanotechnology Training Centre Grant [R25CA154015A]
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Nanomedicines (NMs) offer new solutions for cancer diagnosis and therapy. However, extension of progression-free interval and overall survival time achieved by Food and Drug Administration-approved NMs remain modest. To develop next generation NMs to achieve superior anticancer activities, it is crucial to investigate and understand the correlation between the physicochemical properties of NMs (particle size in particular) and their interactions with biological systems to establish criteria for NM optimization. Here, we systematically evaluated the size-dependent biological profiles of three monodisperse drug-silica nanoconjugates (NCs; 20, 50, and 200 nm) through both experiments and mathematical modeling and aimed to identify the optimal size for the most effective anticancer drug delivery. Among the three NCs investigated, the 50-nm NC shows the highest tumor tissue retention integrated over time, which is the collective outcome of deep tumor tissue penetration and efficient cancer cell internalization as well as slow tumor clearance, and thus, the highest efficacy against both primary and metastatic tumors in vivo.
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