13ª Semana Integrada do Instituto de Física de São Carlos

Characterization of a dimerized indocyanine green nanoemulsion as a photothermal agent

21 de ago. de 2023 14:00

1h 30m

Salão de Eventos USP

Normal 14h00 - 15h30

Descrição

Photothermal therapy (PTT) has emerged as a promising non-invasive approach for cancer treatment, harnessing the conversion of light energy into heat to selectively destroy cancer cells while minimizing damage to healthy tissues. (1) However, the photostability limitations of light-absorbing agents like Indocyanine green (ICG) and other organic dyes present a significant obstacle to the effectiveness of PTT. (2) To address this challenge, this study explores the utilization of nanotechnology, specifically ICG as a surfactant in a nanoemulsion (Nano-dICG). Nano-dICG engineering promoted the formation of stable ICG dimers in the emulsion shell, resulting in enhanced photostability even during prolonged light exposure. (3) The characterization of Nano-dICG involved multiple techniques. High-performance liquid chromatography (HPLC) was employed to determine its chemical composition, purity, and molecular weight distribution. Transmission electron microscopy (TEM) provided detailed insights into the size, shape, and structural integrity of the Nano-dICG particles, allowing for morphological assessment. UV-Vis spectroscopy was employed to measure absorbance properties across various wavelengths, revealing the light absorption capabilities and spectral characteristics, including the formation of self-assembled J-aggregates. Fluorescence spectroscopy examined the emission of fluorescence signals, indicating a decrease in fluorescence compared to the monomeric counterpart. To evaluate the heat conversion and photostability properties of Nano-dICG, a laser (810 nm, 1 W/cm²) was utilized, and the heat production performance was assessed using a thermocouple and thermographic camera. These measurements facilitated the quantification and visualization of the photothermal conversion efficiency in vitro, which revealed a 2-fold increase in photothermal conversion efficiency and 4-fold slower rate of photodegradation compared to regular ICG. Phantom models demonstrated a substantial improvement in heat production following irradiation, reaching 129 °C for Nano-dICG and only 38°C for ICG. Furthermore, an in vivo experiment was conducted using Balb/c mice with 4T1 orthotopic tumors to compare the PTT efficiency of Nano-dICG with that of free ICG molecules and ICG-loaded liposomes. After the intravenous injection of the compounds and the start of the laser irradiation (825 nm, 0.65 W/cm²), heat production was monitored using a thermographic camera. The results of this experiment showed a 2-fold increase in heat production of Nano-dICG compared to regular ICG or liposome ICG. Overall, the development of Nano-dICG as a stable and efficient light-absorbing agent gives an important insight in overcoming the photostability limitations associated with monomeric cyanine dyes.

Referências

1 WEN, Y.; SCHREIBER, C. L.; SMITH, B. D. Dual-targeted phototherapeutic agents as magic bullets for cancer. Bioconjugate Chemistry, v. 31, n. 3, p. 474-482, Jan. 2020. DOI: https://doi.org/10.1021/acs.bioconjchem.9b00836.

2 PELLE, G. D. et al. Cyanine dyes for photo-thermal therapy : a comparison of synthetic liposomes and natural erythrocyte-based carriers. International Journal of Molecular Sciences, v. 22, n. 13, p. 6914-1-6914-16, July 2021.

3 KWON, N.; JASINEVICIUS, G. O.; KASSAB, G.; DING, L.; BU, J.; MARTINELLI, L. P.; FERREIRA, V. G.; DHALIWAL, A.; CHAN, H. H. L.; MO, Y.; BAGNATO, V. S.; KURACHI, C.; CHEN, J.; ZHENG, G.; BUZZÁ, H. H. Nanostructure-driven indocyanine green dimerization generates ultra-stable phototheranostics nanoparticles. Angewandte Chemie International Edition, v. 62, n. 28, p. e202305564-1-e202305564-11, July 2023. DOI: https://doi.org/10.1002/anie.202305564.