Polymersomes for targeted molecular and chemo-therapy of hematological malignancies
Due to the COVID-19 crisis the PhD defence of Wenxing Gu will take place (partly) online.
The PhD defence can be followed by a live stream.
Wenxing Gu is a joint PhD student in the research group Biomolecular NanoTechnology (BNT). His supervisors are prof.dr. Jeroen J.L.M. Cornelissen from the Faculty of Science and Technology, and prof. dr. Zhiyuan Zhong from Soochow University (P.R. China).
The concept of targeted nanomedicines for cancer therapy, inspired by missiles that accurately hit and destroy the aimed objectives, has attracted overwhelming interest from the academia, to healthcare industry and the public. It was hoped that vehicles would carry and specifically deliver anticancer agents into the tumor cells, just like transferrin transporting iron into the needed cells in human being. This vehicle-mediated, enhanced and tumor-selective delivery was anticipated to not only boost the therapeutic efficacy but also minimize the off-target effects, which are often dose-limiting, of highly potent chemo drugs. The immense interest in targeted nanomedicines also stems from the fact that they possibly provide imminent treatments for intractable brain tumors, multi-drug resistant (MDR) tumors, metastatic tumors and relapsed tumors, which constitute the most formidable clinical challenges, by transporting therapeutic agents across the blood-brain barriers, evading the MDR pathways, inhibiting migratory tumor cells, and eliminating the cancer stem cells, respectively. The past decade has witnessed exciting proof-of-concept results using targeted systems in different tumor models.
It has to be noted that the performance of targeted cancer nanomedicines is critically dependent on the vehicles’ properties (size, surface charge, stability, degradability, safety, etc.), ligands (nature, ligation chemistry, density, availability, etc.), therapeutic agents (type, target, loading content and efficiency, release, etc.) and indications (tumor category, volume, stage, receptor density, heterogenicity, accessibility, etc.) that interplay intimately with one another. Among them, the selection of ligands and therapeutic agents are the decisive factors to the specificity of targeted cancer nanomedicines. In addition, the human tumors are very complicated and can vary to a great extent in receptor density, heterogenicity, and accessibility from different tumor types and subtypes, volumes, and stages. Even for the same subtype of tumor, patients may respond differently to the same targeted nanomedicines. Hence, patients have to be screened and only tumors highly expressing target receptors should be selected.
The aim of his thesis is to design advanced, effective and targeted polymersomal nanoformulations for improved cancer therapy. Of particular focus on their use in the targeted molecular and chemo-therapy of hematological malignancies (multiple myeloma and acute myeloid leukemia) and solid tumors (ovarian carcinoma). To achieve this goal, ligands, carriers, drugs and several other aspects should be taken into consideration. In his thesis, a series of targeted (CD44, CXCR4 and HER2) polymersomal nanoformulations based on reduction-sensitive and biocompatible nanomaterials loaded with anticancer drug (epirubicin, vincristine sulfate and quizartinib) were designed for multiple myeloma, acute myeloid leukemia or ovarian carcinoma therapy.
The nanocarriers were developed from a robust and reduction-sensitive polymersomal system based on our proprietary dithiolane trimethylene carbonate (DTC) technology. This system held the features that superb stability in circulation and glutathione-responsive rapid drug release in cells. The results present in his thesis show how to design vary targeted nanomedicines for vary patients from aspects of receptors, ligands, drugs, nanocarriers and tumors, also hopefully give inspirations to more researchers in the development of precision therapy and personalized nanomedicine.