Logo de 22nd International Symposium on Bioluminescence and Chemiluminescence & 20th International Symposium on Luminescence Spectroscopy
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Logo 22nd ISBC & 20th ISLS


Analytical, clinical and medical applications of luminescence

Enhancing Targeted Drug Delivery Systems through the Integration of BODIPY Fluorescent Probes in Nanocomposites for Theranostic Applications in Lung Cancer

Norma L. Zuluaga1, Beatriz S. Cugnasca2, Alcindo A. dos Santos2, Yuli Y. Serna1, Henning Ulrich1, Sérgio H. Toma2, Koiti Araki2, Iolanda M. Cuccovia1

1University of São Paulo, Department of Biochemistry, Brazil., 2University of São Paulo, Department of Chemistry, Brazil.

E-mail: luciabz@icb.usp.br

Introduction: BODIPY (boron-dipyrromethene) fluorescent dyes represent a versatile class of molecules that have significantly impacted various fields, including biotechnology, materials science, and chemical biology. In drug delivery systems, conjugating BODIPY dyes to carriers enables the monitoring of drug release kinetics, intracellular transport, and enhances the overall efficiency and specificity of drug delivery. Objective: Improve a nanocomposite with fluorescent probe BODIPY as a theranostic tool for lung cancer. Materials and Methods: The synthesis of the BODIPY nucleus starts with an aldehyde precursor. Following three reaction steps involving oxidation and complexation, the BODIPY nucleus is achieved with an overall yield ranging from 40% to 45%. Large unilamellar vesicles (LUV), composed of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), a negatively charged lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (POPG), and cholesterol (Chol) were prepared by extrusion through polycarbonate filters. Dynamic Light Scattering Measured LUVs diameter and zeta potential in a Zetasizer Nano 317. The iron oxide nanoparticles, and the aptamers were prepared using standard procedures. Fluorescence was measured in a Hitachi F 7000 fluorimeter. internalization of bodipy in cells was observed using an EVOS FLoid Imaging System. The toxicity of the compounds was determined by MTT assay in HL60 cells. Results: The integration of BODIPY fluorescent into liposomes was assessed using fluorescence analysis. The fluorescence spectra of BODIPY (excited at 440nm) exhibited a peak at 515nm. Upon addition of LUV (large unilamellar vesicles), the emission intensity increased without altering the peak wavelength. This observation confirmed the interaction between LUV and BODIPY, enabling the generation of binding isotherms for this interaction. The internalization of BODIPY into HL-60 cells was evaluated, demonstrating that both free BODIPY and BODIPY conjugated to liposomes were capable of internalizing into the cells. Liposomes and BODIPY, at concentrations of 20mM and 0.01mM, respectively, did not exhibit toxicity after 48 hours of incubation with cells. Furthermore, when all four components were combined at the same concentrations, no toxicity was observed for HL-60 cells. Conclusion: our work has resulted in the successful development of a stable nanocomposite equipped with an embedded fluorescent probe. This achievement holds great potential as a versatile theranostic tool.

Keywords: Bodipy; Liposome; Theranostic.

Acknowledgments: IMC, BSC, and AAS thank FAPESP (Proc. 2013/08166-5, 2018/21489-1 and 2019/07634-1), KA thanks CNPq 442599/2019-6, IMC thanks CNPq, INCT-FCx, and NAP-FCx. NBZ thanks CNPq 161545/2021-1.

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