Size-Optimized Ultrasmall Porous Silica Nanoparticles Depict Vasculature-Based Differential Targeting in Triple Negative Breast Cancer

Shreya Goel, Carolina A. Ferreira, Prashant Dogra, Bo Yu, Christopher J. Kutyreff, Cerise M. Siamof, Jonathan W. Engle, Todd E. Barnhart, Vittorio Cristini, Zhihui Wang, Weibo Cai

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Rapid sequestration and prolonged retention of intravenously injected nanoparticles by the liver and spleen (reticuloendothelial system (RES)) presents a major barrier to effective delivery to the target site and hampers clinical translation of nanomedicine. Inspired by biological macromolecular drugs, synthesis of ultrasmall (diameter ≈12–15 nm) porous silica nanoparticles (UPSNs), capable of prolonged plasma half-life, attenuated RES sequestration, and accelerated hepatobiliary clearance, is reported. The study further investigates the effect of tumor vascularization on uptake and retention of UPSNs in two mouse models of triple negative breast cancer with distinctly different microenvironments. A semimechanistic mathematical model is developed to gain mechanistic insights into the interactions between the UPSNs and the biological entities of interest, specifically the RES. Despite similar systemic pharmacokinetic profiles, UPSNs demonstrate strikingly different tumor responses in the two models. Histopathology confirms the differences in vasculature and stromal status of the two models, and corresponding differences in the microscopic distribution of UPSNs within the tumors. The studies demonstrate the successful application of multidisciplinary and complementary approaches, based on laboratory experimentation and mathematical modeling, to concurrently design optimized nanomaterials, and investigate their complex biological interactions, in order to drive innovation and translation.

Original languageEnglish (US)
Article number1903747
JournalSmall
Volume15
Issue number46
DOIs
StatePublished - Nov 1 2019

Keywords

  • mathematical modeling
  • pharmacokinetics
  • positron emission tomography
  • tumor microenvironment
  • ultrasmall porous silica

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Chemistry(all)
  • Materials Science(all)

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