Doctoral themes 2023

 Magnetic-propelled nanovehicles for delivery of new cancer multidrug resistance reversing agents 

Supervisors

Carlos Balaizão,  carlos.baleizao@tecnico.ulisboa.pt

Andreia Valente, amvalente@ciencias.ulisboa.pt

Registration Institution

Instituto Superior Técnico

Project description

 Cancer is the second leading cause of death worldwide. A severe limitation of drugs in clinical use for cancer treatment is multidrug resistance (MDR). We have recently developed silver(I) complexes that specifically target a resistant ovarian cancer subtype by inducing a new form of programmed cell death called paraptosis, a possible DISRUPTIVE approach to overcome apoptosis resistance. Yet, despite these promising results, the in vivo administration of these compounds has been challenging due to low solubility in aqueous media.

In this project NEW silver(I) compounds will be developed, using a structure-activity rationale to select the best MDR reversing agents. For efficient and targeted delivery of the new compounds, these will be incorporated in NOVEL enzyme-triggered nanovehicles with magnetic propulsion. These have a superparamagnetic core used to drive the accumulation of the nanovehicles at the tumor site, and a PLGA shell able to carry and protect the hydrophobic cargo. The shell is degraded only intracellularly, by enzymes over-expressed in cancer cells.

This multidisciplinary project offers excellent advanced training in organic/inorganic synthesis and polymer/nanomaterials preparation, using a wide range of characterization techniques, such as FTIR, NMR, MS, UV-Vis., Fluorescence Spectroscopy, Light scattering, Electronic Microscopy, and Confocal Microscopy. The project includes a six-month mission at the University of Alcalá de Henares (Spain) for the preparation and characterization of superparamagnetic nanoparticles.

This challenging project offers the opportunity for a major contribution to the field of cancer MDR, both in fundamental science, and as a real possibility to fight several untreatable cancers.

Keywords

Silver(I) complexes

Cancer multidrug resistance

Enzyme-triggered nanovehicles

Magnetic propulsion