#02477Stimuli-responsive platforms for in vitro cell growth and cancer therapy: towards precision medicine

J. Design and scaling up of theranostic nanoplatforms for health: towards translational studies
S. Forciniti 1, V. Onesto 1, F. Serio 1, N. Silvestri 2, C. Camargo De Oliveira 3, T. Pellegrino 2, L.L. Del Mercato 1.
1Institute Of Nanotechnology, National Research Council (cnr‐nanotec), 73100 Italy - Lecce (Italy), 2Istituto Italiano Di Tecnologia, Via Morego 30, 16163 Genoa, Italy. - Genova (Italy), 3Laboratory Of Inflammatory And Neoplastic Cells, Cell Biology Department, Section Of Biological Sciences, Universidade Federal Do Parana ́, Av Cel Francisco H Dos Santos, S/n, Cep 81530-980 Curitiba, Pr, Brazil - Curitiba (Brazil)

Abstract

The design of powerful in vitro cell culture platforms employed in the precision medicine field can contribute to predict patient’s response to cancer treatment [1]. Polymeric electrospun nanofibers manufactured in a controlled manner possess a dual ability to support in vitro cell growth by mimicking the extracellular matrix (ECM)  and to control drug release [2]. For this purpose, we established an electrospinning method to produce biocompatible blended polyvinyl-alcohol (PVA)/ gum arabic (GA) ECM-like nanofibers for in vitro cell cultures capable of delivering nanocomposites for biomedical application [3]. After the development and the characterization of the PVA/GA ECM-like nanofibers, heat treatment was used to crosslink the nanofibers and biocompatibility was evaluated, demonstrating the ability of the developed platform to provide a cell culture-friendly environment. As GA-gold nanoparticles (GA-AuNPs) in non-cytotoxic concentrations can reduce invasion and colony formation of metastatic melanoma cells [4], the crosslinked nanofibers were functionalized with GA-AuNPs and its cellular delivery was evaluated. GA-AuNPs were efficiently adsorbed onto the PVA/GA nanofibers surface and the system effectively delivered the nanocomposites to metastatic melanoma cells. In addition, we produced biocompatible nanofibers of polycaprolactone loaded with iron magnetic nanoparticles as heat mediators to introduce a multi-therapeutic approach based on the combination of the magnetic hyperthermia with the chemotherapeutic effects of doxorubicin [5]. The drug-free magnetic fibers showed high biocompatibility when used as substrates for growing fibroblast cells with no adverse effects on cell adhesion and viability in absence of magnetic hyperthermia exposure. On the contrary, the fibers containing both magnetic nanocubes and doxorubicin showed significant cytotoxic effects on cervical cancer cells following the exposure to magnetic hyperthermia. Notably, the magnetic hyperthermia field conditions are those of clinical use and the combination of heat damage by magnetic hyperthermia with enhanced diffusion of doxorubicin at therapeutic temperature are responsible for a more effective oncotherapy. The research leading to these results was supported from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No 759959, ERC-StG “INTERCELLMED”).

References

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2. Jin L et al, Macromol. Mater. Eng, 2017; 302, 1–9;

3. Serio F. et al, Int J Biol Macromol. 2021; 188:764-773;

4. Gonçalves P. et al, Eur J Pharm Biopharm 2020; 157:221-232;

5. Serio F. et al, J Colloid Interface Sci. 2022; 607 (Pt 1):34-44.