CAREER: Self-Assembly of Anti-Cancer Drugs into Well-Defined Supramolecular Nanostructures

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This Career Award by the Biomaterials Program in the Division of Materials Research to Johns Hopkins University will support the development of new strategies to direct the self-assembly of anticancer drugs into supramolecular nanostructures with well-defined structural features for increased drug loading capacities. Current approaches for the delivery of cancer chemotherapeutics in using nanoscale carriers through encapsulation within liposomes or polymeric nanoparticles, or by conjugation to hydrophilic polymers tend to modify the drug's pharmacokinetic properties and biodistribution. Additionally, there are inherent difficulties in achieving a high and quantitative drug loading per carrier. This project explores the potential molecular interactions that drug molecules can offer for self-assembly into a variety of nanostructures, and seeks to understand how these supramolecular nanostructures affect the ability of the system to release their therapeutic payloads. The quantitative drug loading in the prepared nanostructures would be ensured by the very nature of themolecular design features. Notably, the proposed drug delivery system does not require any additional carriers, easing potential concerns associated with the long term toxicity of synthetic drug carriers. Since targeted drug delivery and controlled release are the foundations in the development of effective chemotherapies for tumor treatments, the fundamental knowledge developed from the proposed research activities will open new avenues for cancer chemotherapies. The proposed education plan aims to promote training, learning, and teaching of students at all levels, and broadening the participation of students from underrepresented groups in the Baltimore City Public School system. For K-12 students in particular, the provision of an experiential learning opportunity in drug delivery research would spark their interest in science, and helps in creating the next generation of young scientists.Chemotherapy is currently the most effective method available for the treatment of metastatic cancers, producing the highest survival and cure rates. The toxicity of anticancer drugs to healthy cells, however, requires the development of methodologies that can deliver these drugs exclusively to the tumor sites at higher doses. A successful delivery strategy promises immense benefits through both the reduction of side-effects and a greater treatment efficacy. Accordingly, the creation of nano-sized vehicles for the effective delivery of hydrophobic anticancer drugs to tumor sites has garnered justifiable attention in cancer chemotherapy research for several decades. A fundamental limitation of this strategy, however, is the difficulty in achieving a high and quantitative drug loading content per carrier. Also, concerns regarding the short-term and long-term toxicities of the synthetic nanomaterial carriers other than the drugs to be delivered often lead to exhaustive preclinical evaluation, representing a difficult hurdle for the drug's translation into clinical use.The proposed work aims to address these challenges though the development of delivery vehicles made of anticancer drugs themselves. Such drug nanostructures would contain a specific drug content, and do not require the use of additional drug carriers.The multidisciplinary nature of drug delivery research provides ample opportunities for education and outreach.The proposed educational plan is expected to have a significant impact on the interests and STEM careers of participating students. With programs designed to educate and provide hands-on research experience, the plan aims to increase interest in the pursuit of higher education and doctoral studies of STEM for high school and undergraduate students respectively. These experiences will reinforce their interests in the various science related disciplines and boost confidence in their abilities through programs that focus on creative problem solving and teamwork, such as the proposed Engineering Innovation initiative.