Submitter withdrawn post acceptance 21st International Conference on Biological Inorganic Chemistry 2025

Metal-involving anticancer nanoformulations for theranostic applications (#579)

Alessia Sambugaro 1 2 , Riccardo Po 1 2 , Irina Ivanova 3 , Marco Giarola 1 4 , Emiliano cazzola 5 , giacomo Martinelli 2 , Erik Murador 1 2 , Tatyana Pleshakova 3 , Marina Scarpa 6 , Valentina oliveri 7 , Chiara Nardon 1 2
  1. University of Verona, Verona, ITALY, Italy
  2. Biotechnology, University of Verona, verona, Italia
  3. Laboratory of Single Biomacromolecules Research, IBMC, Moscow
  4. Centro Piattaforme Tecnologiche, University of Verona, verona, Italia
  5. Radiopharmacy, IRCCS Sacro Cuore Hospital, Negrar (Verona), Italy
  6. Physics, University of Trento, Povo (trento), Italy
  7. Chemical sciences, University of Catania, Catania

AIMS

Nanosystems offer benefits in terms of permeability and retention, drug stability, superior pharmacokinetics, and the possibility of achieving controlled/targeted drug release.1 Among all nano-sized delivery platforms, biocompatible cellulose nanocrystals (CNCs) emerged as candidates whose applications range from tissue regeneration to wound healing.2 Their distinctive rod-like shape (able to enhance circulation time and cellular uptake compared to spherical alternatives)3 makes them particularly attractive not only as therapeutics but also as novel diagnostic tools. To explore their potential, we investigated the binding of different endogenous/exogenous metals and, subsequently, the interaction with the clinically-established model drug Doxorubicin (DOX). The obtained results paved the way to the study of the combination with Doxycycline (DC), followed by its interaction with copper. Preliminary tests were performed on CNCs for the coordination of some radionuclides, like 61Cu and 89Zr.

METHODS

Carboxylate groups were introduced on CNCs surface by a TEMPO-catalyzed oxidation which allowed the electrostatic binding of DOX/DC. The nanoformulations were characterized by different techniques and drug release studies were performed over time at different pH values, mimicking physiological/pathophysiological conditions. Furthermore, the antiproliferative activity was tested in vitro on selected human cancer cell lines. The binding of different metals (chloride salts of Na, K, Cu, Zn, Tb) was studied in MOPS buffer changing metal concentrations and temperature.

RESULTS

The negative surface charge of CNCs allowed the binding of large amounts of organic drugs while leading to aggregation phenomena under certain experimental conditions during the interaction with different metals. XRD investigations underlined the importance of sample preparation steps and allowed a deeper understanding of the nanorod behavior layer-after-layer.

Drug release kinetic profiles proved promising for future oncological applications in vivo and the in-depth studies of the interesting properties of the nanoformulation involving copper are ongoing. The antiproliferative effects were checked on lung, prostate and triple-negative breast cancer cells.

CONCLUSIONS

The binding of therapeutics combined with improved antiproliferative effects on cancer cells due to the presence of the metal center highlighted the bio-inorganic drug-delivery platform potential. This work, at the interface between inorganic chemistry/radiochemistry and biology, paves the way to future applications in the theragnostic field.

  1. 1. Yao, Y. et al. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front Mol Biosci 7, 193 (2020).
  2. 2. Luo, H. et al. Advances in tissue engineering of nanocellulose-based scaffolds: A review. Carbohydrate Polymers 224, 115144 (2019).
  3. 3. Albanese, A., Tang, P. S. & Chan, W. C. W. The Effect of Nanoparticle Size, Shape, and Surface Chemistry on Biological Systems. Annual Review of Biomedical Engineering 14, 1–16 (2012).