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Nanoprobe designed to help combine lung cancer treatments

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In a recent study published in the journal LangmuirResearchers have developed a novel photosensitive nanoprobe for efficient targeted drug accumulation, optimal thermal conversion efficiency, and singlet oxygen generation for photodynamic or photothermal therapy during lung cancer treatment.

Study: A new nanoprobe for targeted imaging and photothermal/photodynamic therapy of lung cancer. Image Credit: Create Jobs 51/Shutterstock.com​​​​​​​​

The nanoprobe consists of indocyanine green (ICG) near-infrared (NIR) photosensitive drug, porous ferric oxide (Fe3O4) nanoparticles, and a hyaluronic acid (HA) modifier

It has also been shown to exhibit excellent ICG loading, stability in organic solvents, and specific targeting of lung cancer cells under 808nm laser irradiation.

Photothermal and photodynamic treatment of lung cancer

Currently, ICG is the most commonly used hydrophobic NIR photosensitive reagent in the diagnosis, treatment and early detection of tumors based on photothermal (PTT) and photodynamic (PDT) therapy.

In PTT, ICG efficiently converts light energy into heat, while in PDT, it uses light energy to generate singlet (least excited) oxygen molecules at a specific irradiation wavelength from NIR. However, its nanoprobing and sanative applications are hampered by its several characteristics, such as instability, clumping and decomposition in polar solvents, poor tumor targeting ability and rapid wilting in plasma medium due to its low half-life 2−4 min.

As a solution, Fe3O4 nanoparticles, which are widely used in nuclear magnetic resonance (NMR) as a contrast agent, can be chemically etched to form a porous structure and used as a drug carrier of ICG to affect specific organs, tissues or cells under the effect of a magnetic adscititious domain.

Additionally, a major component of the extracellular matrix, HA, can be used as an ICG modifier and protective agent for the Fe/ICG complex due to its biocompatibility, biodegradability, and nature of binding to overpopulated CD44 receptors. on the surface of the mutated. cells.

About the study

In this study, the researchers synthesized the Fe/[email protected] complex for targeted drug delivery to lung cancer cells. First, the Fe3O4 nanoparticles of uniform size and dispersibility were synthesized from FeCl24H2O, FeCl36H2O, poly(ethylene glycol) (PEG) and dilute ammonia using the co-precipitation method at 50°C.

After that, porous Fe3O4 nanoparticles were synthesized using ammonium acetate as an etchant, followed by ICG loading into the corresponding nanopores. Finally, the Fe/[email protected] The complex was synthesized by suspending Fe/ICG in 10 mL of deionized water containing HA (0.5 mg/mL) for several hours.

Subsequently, the prepared nanoprobe complex was characterized and its biocompatibility, biodegradability, cellular uptake, T2-MR imaging, in vitro and in vivo processing were analyzed against cultured A549 cells.

Fluorescence intensity inside A549 cells was quantitatively analyzed by flow cytometry after several time intervals.

Comments

Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images showed that Fe/[email protected] The complex exhibited a fuzzy microstructure with a clear organic layer after ICG loading and HA modification, indicating successful loading of both materials onto the porous Fe3O4 nanoparticles.

UV−vis analysis revealed an ICG loading of 17.6% and a temperature of 61.5°C on the Fe3O4 nanoparticles. CCK-8 and apoptosis analysis revealed that ICG had no noticeable cytotoxicity in the concentration range of 0-40 μg/mL and less than 2% apoptotic cells at the highest concentration, proving excellent biocompatibility.

Moreover, the internal fluorescence of A549 cells incubated with Fe/[email protected] The complex with 808 nm laser irradiation was stronger than that of the pure ICG complex.

Moreover, the intensity of the fluorescence emission directly depended on the incubation time inside the A549 cells.

Fluorescence intensity after 12 hours of incubation was significantly higher than after 2 hours.

In vitro analysis using cell double staining and a laser confocal microscope revealed a large number of dead cancer cells for Fe/[email protected] complex than pure ICG and pure Fe3O4 nanoparticles.

conclusion

In summary, the researchers in this study synthesized Fe/[email protected] complex for PTT and PDT based diagnosis and treatment of lung cancer cells such as A549 cells.

Under laser irradiation at 808 nm, the Fe/[email protected] The complex exhibited improved incubation time-dependent fluorescence intensity, targeted imaging and killing of cancer cells, excellent biocompatibility, long-lasting drug carryover, satisfactory ICG drug loading of 17.6%, and no cytotoxicity. Thus, Fe/[email protected] The complex nanoprobe is a promising candidate for precision lung cancer phototheranostics.

Read on: Advances in Pulmonary Drug Delivery with Nanoparticles.

Reference

Sun, X., Xu, Y., Guo, Q., Wang, N., Wu, B., Zhu, C., Zhao, W., Qiang, W., Zheng, M., (2022) A novel Nanoprobe for targeted imaging and photothermal/photodynamic therapy of lung cancer, Langmuir. Available at: https://pubs.acs.org/doi/10.1021/acs.langmuir.1c02434

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