Development of SERS-active, NIR-responsive gold nanourchins (GNUs) for stimuli-triggered theranostic applications against hematological malignancies
Recently, the development of smart nanomaterial-based therapeutics has substantially advanced, mostly due to their capacity to function as alternatives to common approaches. Moreover, the vast array of bio-chemical and physical features like high surface area and interesting optical properties render them useful for multiple purposes such as therapy or improved diagnosis. Among young people, hematological malignancies (HMs) are some of the most common forms of cancer, resulting in unprecedented rates of long-term side-effects such as cognitive and cardio-pulmonary impairments that can greatly reduce their life-quality. The most promising chemotherapeutics employed against HMs at present are Tyrosine Kinase Inhibitors (TKIs), but these molecules still have disadvantages like insufficient solubility, bio-availability and specificity. Hence, with the intention of improving treatment success and reducing side-toxicities, this project aims to design a NIR-responsive urchin-like gold nano-agent (GNU) by encapsulating TKIs in hydrophobic pockets within an amphiphilic polymeric shell surrounding the gold core. By targeting the nanostructures to cancer cells using antibodies specific for an internalizing epitope, the particles are bound for the lysosomal compartment, where they encounter conditions such as hydrolytic enzymes and low pH. The 'smart', stimuli-sensitive polymeric shell developed herein will respond and react to these stimuli, ensuring intracellular drug release exclusively within the target cells. Additionally, the GNU plasmonic cores can confer diagnosis value to the system, due to their exceptional optical properties namely a high SERS-active background signal. Tailoring particle morphology can tune the plasmonic response into the NIR ‘biological window’ domain, a feature that, in combination with the time-effective and non-invasive character of the confocal Raman microscopy technique, offer real potential for implementation of this system in further theranostic applications.
Romanian National Authority for Scientific Research, UEFISCDI
Program from PNIII: Human Resources
Budget: 123.473 RON (~ 25.340 EUR)
Period: 1 September 2020 - 31 August 2021
Contract no.: 159/2020
Institution of implementation: Nanobiophotonics and Laser Microspectroscopy Center; Interdisciplinary Research Institute in Bio-Nano-Sciences; Babes-Bolyai University.
Project Leader: Dr. Andra-Sorina TATAR
Mentor: Dr. Habil. Monica BAIA
The major aim of this project is to develop a ‘smart’ drug-delivery nanosystem with theranostic properties that has the potential to improve the prognosis of patients with hematological malignancies, such as leukemia. More specifically, the therapeutic effect of the nanosystem is based on the release of the TKI drug molecules inside the lysosomes of antibody-targeted cells, based on the stimuli-sensitivity of the polymeric shell developed herein, while its diagnosis value lays in the SERS active properties of the GNU plasmonic cores that have an intrinsic background signal making them highly valuable for potential Raman/SERS microscopy.
Results and Dissemination
Andra-Sorina Tatar, Monica Baia, Klara Magyari, Simion Astilean, Sanda Boca*, Stimuli-Responsive Polymer-Coated Gold Nanourchins for Controlled Delivery of Dasatinib Hydrophobic Tyrosine Kinase Inhibitor, Nanomedicine International Conference and Exhibition NanoMEd 2021, hybrid conference, 20-22 October 2021. Poster.
A.S. Tatar, A. Jurj, A.B. Tigu, A. Florea, I. Berindan-Neagoe, S. Astilean, C. Tomuleasa, S.Boca*, Optimization of tyrosine kinase inhibitor-loaded gold nanoparticles for triggered antileukemic drug release and cytotoxic evaluation, COST Action CA17140, Cancer Nanomedicine - from the bench to the bedside, 25-26 October 2022, Rome, Italy.
manuscript in preparation.
[..under construction.. :) ]