Leveraging Rational Nanoparticle Design for Improved Treatment of Pediatric and Adolescent Cancers

Abstract

The purpose of this proposal is to utilize a high-throughput pan-cancer screening approach (PRISM) to identify effective therapeutic nanoparticle formulations for the treatment of cancers found in children, adolescents, and young adults. The scope of the project reported herein comprised 1) the synthesis and characterization of a library of fluorescently-labeled nanoparticles with diverse surface chemistries, including tumor targeting and penetrating peptide motifs, 2) profiling of nanoparticle-cell associations via flow cytometry in a select number of cell lines, originating from patients classified as children, adolescents, or young adults, and 3)the screening of this nanoparticle library via the PRISM platform to identify comprehensive data on the structurefunction relationship between nanoparticles and specific cell types, elucidate uptake trends across specific lineage sub-analyses, as well as highlight differences in nanoparticle uptake in pediatric, adolescent, and adult cancer cell lines. The major findings resulting from this work include development and validation of the flow-based PRISM screen to sort and analyze nanoparticle-cell interactions through the use of correlative genomics, the identification of the predominant nanoparticle parameters driving particle-cancer cell interactions, evaluation of the effects of cancer cell line lineage and doubling time on nanoparticle uptake, and the identification of a nanoparticle-specific biomarker that can be used to predict the propensity of a cancer cell to take up nanoparticles as well as the extension of these findings to cell lines derived from patients classified as children, adolescents, and young adults, with specific emphasis on nervous system and bone cancers.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2020
Accession Number
AD1110704

Entities

People

  • Natalie Boehnke

Organizations

  • Massachusetts Institute of Technology

Tags

DTIC Thesaurus Topics

  • Biomedical And Dental Materials
  • Biomedical Engineering
  • Biomedical Research
  • Blood-Brain Barrier
  • Bone Cancer
  • Cell Line
  • Cells
  • Central Nervous System
  • Chemistry
  • Data Analysis
  • Health Services
  • Materials Science
  • Medical Personnel
  • Neoplasms
  • Nervous System
  • Students
  • Therapy

Readers

  • Gender and Food Studies
  • Nanocomposite Materials Science
  • Oncology

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech