Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors

Jaehong Key, Anna Lisa Palange, Francesco Gentile, Santosh Aryal, Cinzia Stigliano, Daniele Di Mascolo, Enrica De Rosa, Minjung Cho, Yeonju Lee, Jaykrishna Singh, Paolo Decuzzi

Research output: Contribution to journalArticlepeer-review

103 Citations (Scopus)

Abstract

Most nanoparticles for biomedical applications originate from the self-assembling of individual constituents through molecular interactions and possess limited geometry control and stability. Here, 1000 × 400 nm discoidal polymeric nanoconstructs (DPNs) are demonstrated by mixing hydrophobic and hydrophilic polymers with lipid chains and curing the resulting paste directly within silicon templates. By changing the paste composition, soft- and rigid-DPNs (s- and r-DPNs) are synthesized exhibiting the same geometry, a moderately negative surface electrostatic charge (-14 mV), and different mechanical stiffness (∼1.3 and 15 kPa, respectively). Upon injection in mice bearing nonorthotopic brain or skin cancers, s-DPNs exhibit ∼24 h circulation half-life and accumulate up to ∼20% of the injected dose per gram tumor, detecting malignant masses as small as ∼0.1% the animal weight via PET imaging. This unprecedented behavior is ascribed to the unique combination of geometry, surface properties, and mechanical stiffness which minimizes s-DPN sequestration by the mononuclear phagocyte system. Our results could boost the interest in using less conventional delivery systems for cancer theranosis.

Original languageEnglish
Pages (from-to)11628-11641
Number of pages14
JournalACS Nano
Volume9
Issue number12
DOIs
Publication statusPublished - 2015 Oct 21

Bibliographical note

Funding Information:
This work is partially supported by the European Research Council under the European Union''s Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement No. 616695 and the Houston Methodist Research Institute. The authors acknowledge the help of Matt Landry forthe graphical work; the Advanced Cellular & Tissue Imaging Core and the Preclinical Imaging Core at HMRI (Houston, TX); and the Microfabrication Facilities at the Istituto Italiano di Tecnologia (Genova, Italy). J.K. synthesized DPNs and participated in all experiments; A.L.P. helped with the synthesis of DPNs, cell uptake and intravital microscopy experiments; F.G. fabricated the silicon templates for the precise synthesis of DPNs; S.A. synthesized the lipid-DOTA chains, helped with the PET/CT and half-life circulation time experiments; C.S. performedthe nanotoxicological experiments, D.D.M. helped with the flow cytometry analysis; E.D.R. performed the intravital microscopy experiments; M.C. synthesized the iron oxide nanocubes; Y.L. performed the atomic force microscopy experiments; J.S. performed the mathematical analysis; P.D. designed and coordinated the research, analyzed the data, and wrote the manuscript. All authors analyzed and discussed the results.

Publisher Copyright:
© 2015 American Chemical Society.

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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