As a researcher deeply committed to advancing cancer therapeutics, I am tackling the formidable challenge of malignant mesothelioma-a cancer notorious for its aggressiveness and resistance to conventional treatments. My project centers on the development of next-generation targeted therapies by integrating nanobiotechnology, advanced disease modeling, and innovative chemical biology approaches.

The core of my research is the precise targeting of mesothelioma cells using engineered liposomal carriers encapsulating potent small molecule inhibitors of key oncogenic proteins, BUB1 and RUVBL1. To maximize specificity and therapeutic impact, I am functionalizing these liposomes with mesothelin-targeting moieties, exploiting the overexpression of mesothelin on mesothelioma cells. This targeted delivery is critical for enhancing drug accumulation at the tumor site and minimizing off-target effects.

To rigorously evaluate the efficacy and translational potential of these therapies, I am employing a comprehensive panel of preclinical models. In vitro, I use both established mesothelioma cell lines and patient-derived cancer cells. More importantly, I leverage patient-derived organoid models, which faithfully recapitulate the cellular diversity and microenvironment of human tumors, providing a robust platform for predicting clinical responses. For in vivo validation, I utilize subcutaneous xenograft models, enabling the assessment of therapeutic efficacy and biodistribution in a physiologically relevant context.

A distinguishing feature of my approach is the application of bioorthogonal chemistry to develop advanced antibody-drug conjugates and bispecific antibodies. This strategy allows for the site-specific conjugation of therapeutic payloads and the creation of multifunctional molecules capable of simultaneously engaging multiple tumor targets. By harnessing these cutting-edge techniques, my goal is to pioneer highly selective and potent therapies that can overcome resistance mechanisms and improve outcomes for mesothelioma patients.

Through this integrated and innovative strategy, I aim to contribute transformative solutions to the field of cancer nanomedicine, offering new hope for patients facing this devastating disease.