Why drug resistance is important?
Resistance to drugs is a major challenge that significantly reduces therapeutic efficacy, induces recurrence of disease and generates cross-resistance to a wide spectrum of drugs, resulting in multidrug resistance (MDR). The most recent threat is the extreme case known as extensive drug resistance (XDR). This is an even more ominous condition that can appear as a ‘Diagnose for Death’, if the resistance remains unsolved.
What is the problem?
Among others, unintentional exposure to drugs to normal healthy cells and tissues at sub-threshold dose help them to become resistant to a broad range of drugs. The steady rise in the number and types of drug resistance has increased suffering, therapeutic expense, organ disability and death. Drug resistance phenomena is not restricted to the disease host cells only. In Europe, patients with HIV show even more alarming figure where one in ten HIV case is drug-resistant. From the molecular point of view, a single signalling pathway does not govern MDR. Rather, it is a complex phenomenon with various defence mechanisms that collectively defuse the drug actions including pumping out the drug from the cells. Huge efforts have been made to stop such drug efflux pump but their translation into clinics failed due to high toxicity, lack of specificity, limited efficacy and their ability to alter pharmacokinetic and bio-distribution profiles of the actual parent drugs. Thus a fresh therapeutic protocol is required, which can be custom-tuned to individual resistance type.
Overall objectives of the project
During this fellowship I aimed to develop a novel class of biomimetic remotely responding theranostic (combined diagnosis and therapeutic) molecular “zipper” enabled nanoarchitectures that can respond to stop the drug resistance mechanisms.
I sought to develop nanosystems that are biocompatible, immunologically safe, and compatible to blood and will allow to design its surface with cargo drugs. I envisaged a zipper like molecular architecture using polymeric donor and respective acceptor branches to insulate the cargo drugs, nucleic acids while transported.
I intended to test the NinZA module with a three dimensional multi-cellular spheroid model for a comparative study on the cells resistance to drug response on a real time basis. Thus the nano-architecture platform will probe drug resistance through a controllable on/off switchable model. Furthermore, I sought a series of complementary career skills training that will enhance my research management, leadership, and presentation and teaching skills and make me an exciting EU candidate with translational research goals. This Fellowship helped to gain new scientific and career skills to position me to become a leading independent academic in the interface of chemistry and biology for translational Nanomedicine.
