Brief background of the proposal and its relevance to the CDI’s objectives
Diffuse intrinsic pontine glioma (DIPG) is the single greatest cause of brain tumor-related deaths in children. The location and diffuse nature of the disease prohibit surgical interventions; radiation therapy has proven inadequate for cure; and conventional chemotherapy is ineffective because drug delivery is limited by the intact blood-brain barrier (BBB). This project proposes to develop an innovative strategy for the improved treatment of DIPG using focused ultrasound (FUS)-enabled delivery of dissolvable, 64Cu-doped, chemotherapy-loaded copper nanoclusters (64Cu-CuNCs).
Proposed specific aims
· Optimize the synthesis 64Cu-CuNCs and FUS disruption of the BBB to maximize the delivery of 64Cu-CuNCs to the brain.
· Quantify drug accumulation using FUS-enabled delivery of 64Cu-CuNCs in a murine DIPG model.
· Measure the therapeutic efficacy and safety of 64Cu-CuNCs delivered by FUS in the DIPG model and develop an image-guided drug delivery strategy.
Potential impact on child health
Nanomedicine has shown great potential in cancer diagnosis and therapy. However, the BBB has limited its application. FUS is an effective technique for noninvasive and localized BBB opening. The integration of nanomedicine and FUS provides a therapeutic platform for the treatment of not only DIPG but also other pediatric brain diseases.