WRH Student Seminar: Meher Bhalla & Jasmine Liu

Meher Bhalla: Paediatric rhabdomyosarcoma (RMS), a rare and often ultra-rare malignancy, demands more precise and adaptable treatment strategies. This project develops a next-generation bivalent nanobody-drug delivery system, integrating genomic landscape mapping, click chemistry, and nanochemistry. Using nPEG linkers, the platform enables dual-antigen targeting with simultaneous delivery of therapeutic and imaging agents. Designed for high specificity, reduced toxicity, and real-time monitoring, these bivalent constructs represent an evolution toward third-generation therapeutics. By bridging tumour genomics with nanoscale design, this approach advances precision therapy for RMS and establishes a versatile framework for treating other rare paediatric cancers.

Jasmine Liu: Pediatric glioblastoma (p-GBM) is an aggressive, high-grade glioma for which no standardised treatment currently exists. The blood–brain barrier (BBB) significantly limits the delivery efficiency of most chemotherapeutic agents used in the treatment of p-GBM. This study developed two novel platinum-based nanoparticles with distinct core sizes—platinum nanoclusters (PtNCs, ~2 nm) and platinum nanoparticles (PtNPs, ~10 nm)—functionalised with ankyrons and rabies virus glycoprotein (RVG) peptides to facilitate active targeting of p-GBM and enhance drug delivery efficiency. Both Pt-based formulations demonstrated potent anticancer activity and induced DNA damage in p-GBM cells. Notably, only the ultra-small PtNCs were capable of eliciting oxidative stress within tumour cells. The nanoparticles are designed for administration via intranasal inhalation, a route that enhances patient compliance, particularly in pediatric populations. More importantly, this work opens the possibility of using ultra-small nanoclusters to treat various cancer treatment or brain diseases.