Leveraging Rational Nanoparticle Design for Improved Treatment of Pediatric and Adolescent Cancers
Abstract
Career goals in cancer research: My long-term research interests as an independent investigator are centered around improving the fundamental understanding of nanomaterial systems to rationally address unmet needs in cancer treatment. Specifically, I am focusing on using nanoparticles for the improved treatment of pediatric and adolescent cancers that often do not receive the same attention and resources as more common types of cancer. My undergraduate and graduate work focused on using chemistry tools to design and manipulate complex synthetic systems for biological applications, providing me with the necessary knowledge and tools for rigorous materials synthesis, characterization, and testing. I chose to carry out postdoctoral studies with Prof. Paula Hammond as a Marble Postdoctoral Fellow to systematically explore how modulating chemical properties of nanoparticles affects their fate in vitro and in vivo in order to rationally design a more effective cancer therapy delivery platform. While my training has allowed me to gain the necessary tools to apply my expertise to the development and systematic study of drug delivery systems, these experiences have ultimately highlighted the lack of nanotechnologies being developed for pediatric and adolescent cancers, due to their rarity, and the lack of reliable or established models for testing. The Department of Defense (DoD) BCRP Horizon Award will provide me the opportunity to begin developing therapeutic nanoparticles for the improved treatment of these underexplored cancers and will serve as the springboard needed to continue pursuing these studies in my future independent career. Objective: The objective of this proposal is to utilize a high-throughput pan-cancer screening approach to identify effective therapeutic nanoparticle formulations for the treatment of cancers found in children, adolescents, and young adults. First, a library of nanoparticles (NPs) with diverse surface chemistry families will be generated. Second, the structure–function relationship of NP surface chemistry on particle uptake will be examined and the uptake trends across pediatric, adolescent, and adult cancer cell lines will be analyzed, compared, and contrasted. Third, a cytotoxic agent (cisplatin) will be packaged inside the NP formulations with the highest uptake across the cell lines of interest to examine the therapeutic efficacy as a function of particle surface chemistry and to identify promising therapeutic NP formulations effective in these underexplored cancer cell lines Rationale: According to a 2014 report by the DoD, there are 1.82 million military children, aging from birth to 22 years in age. The odds of being diagnosed with cancer before the age of 20 are 1 in 285. These statistics, when considered in combination, suggest close to 10,000 of these military children may face the challenge of fighting cancer. It is not only the patient who is affected by cancer; friends and family, often comprising active military members as well as Veterans, also bear significant emotional and financial burdens surrounding a child’s cancer treatment. Moreover, successful treatment of cancer often comes at a great cost: greater than 95% of childhood cancer survivors will face significant health issues by the time they reach 45 years of age. And, for the majority of these patients, the adverse health effects are the result of treatment side effects, underscoring the dire need to develop safer, targeted drug delivery platforms for these pediatric and adolescent cancers. Developing such drug delivery systems to advance the treatment of cancers that affect children, adolescents, and young adults is challenging due to the rarity of these cancers, resulting in a lack of patient samples and screening platforms for testing. Therefore, there is a need to look to alternative screening platforms that are able to assess treatment efficacy while capturing the unique nature and heterogeneity of the patient and th
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910257
Entities
People
- Natalie Boehnke
Organizations
- Massachusetts Institute of Technology
- United States Army