Manufacture of biocompatible lead bromide nanocrystals for cancer cell diagnostics


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A recent study published in the Chemical Engineering Journal focuses on the photoluminescence and bioimaging applications of highly biocompatible CsPbBr.3 perovskite nanocrystals enclosed in SiO2 nanocoque.

Study: Application of two-photon photoluminescence and bioimaging of perovskite nanocrystals in monodisperse silica with high biocompatibility. Image Credit: Caleb Foster / Shutterstock.com

Two-photon fluorescent probes composed of synthetic lead can be effectively used for bio-imaging applications such as cancer cell diagnosis, but their low biocompatibility due to the high reactivity and cytotoxicity of lead+2 ions considerably limit their use in the biomedical industry.

Importance of two-photon fluorescence imaging

Early detection and testing are the only effective methods to increase the cancer survival rate. Near infrared (NIR) lasers can be focused on a very small area and have many advantages including excellent spatial accuracy, high penetration, low noise illumination, and minimal oxidative stress to cells. Two-photon luminescence microscopy, using two near infrared (NIR) rays as an excitation signal and resulting in the production of light waves, is considered to be a very effective technique for monitoring cellular activities and detecting early cancer mutations.

Accordingly, the development of high performance, biodegradable and cost effective two-photon fluorescent sensors is of considerable importance in advancing cancer treatment. Biomedical imaging using lanthanide-treated nanocrystals, aggregation-induced luminescence nanomaterials, and II-VI nanoparticles under near infrared laser light has garnered much interest in recent years.

Lead bromide (CsPbBr3) Nanocrystals for bio-imaging applications

Due to their high optical absorption and enhanced photoluminescence, synthetic lead perovskite nanocrystals such as CsPbBr3 have emerged as promising materials for optical and electrical applications. However, due to the inherent instability and cytotoxicity of Pb+2 ions, their applicability in the bio-imaging industry is quite limited.

The silica coating (SiO2) protects lead bromide nanocrystals from reactive species such as moisture, improves photo-stability and reduces dangerous movement of ions, which improves biocompatibility of NCs.

Limitations of the previous methods

Previously, CsPbBr3 Nanocrystals have been embedded inside the silica shells to reduce flicker while improving water resistance and light absorption. However, the nanocrystals produced with this approach are too large for bioimaging applications. Another method uses ultraviolet light to enclose CsPbBr3 nanocrystals less than 3.5 nm thick of SiO2 nano-shells, but UV light has a shallow depth of penetration into human tissue. Therefore, nanocrystals prepared under UV radiation are not suitable for the detection of cancer cells.

A new technique to produce biocompatible CsPbBr3 Nanocrystals

In this work, the researchers developed lead bromide nanocrystals encapsulated in silica nanoshells in a simple one-step nucleation technique and constantly adjusted the thickness of the silica shell between 15 and 60 nm. The surface appearance and crystal architecture of the nanocrystals were examined using a transmission electron microscope. The phase concentration was determined by X-ray diffraction, and the content and oxidation states of NCs were determined by X-ray photoelectron spectroscopy.

Human hepatocellular cancer cells (HepG2) were used to test the cytocompatibility of the lead bromide nanocrystals produced. After washing with a phosphate buffered saline (PBS) solution, the cultured HepG2 cells were transferred to a fresh medium containing lead bromide nanocrystals embedded in SiO.2. CNs entered cancer cells by endocytosis during this process. The cells were rinsed again with PBS solution, and a small amount of PBS solution was added to maintain the moisture content of the cells. Finally, fluorescent images of HepG2 cancer cells were acquired using a laser scanning microscope with an 800 nm laser as the excitation source.

Important research results

The researchers observed that an SiO2 a shell of an appropriate thickness of 30 nm inhibited the agglutination of the nanocrystals and the non-radiative mixing of the charged particles. The produced nanocrystals exhibited high two-photon adsorption and generated peaks of green light at 526nm when excited by an 800nm ​​near infrared laser. The average decay lifetime of lead bromide nanocrystals under two-photon excitation was close to that of single-photon illumination, which is extremely useful for biomedical applications.

After 24 hours of treatment and storage with lead bromide nanocrystals embedded in silica nanoshells, the survival rate of human cancer cells (HepG2) was determined to be 96.21%, confirming the exceptional cytocompatibility of CNs. The cumulative emission intensity of CsPbBr produces3@SiO2 nanocrystals was at least five times that of the control group of nanocrystals.

In short, this research has demonstrated a simple, one-step method for the manufacture of biocompatible lead bromide nanocrystals with useful applications in the field of bio-imaging, in particular the diagnosis of cancer cells.

Continue Reading: An Overview of Thin Films of Gold: From Sensors to Cell Culture.

Reference

Zhong, CY et al. (2021). Application of two-photon photoluminescence and bioimaging of perovskite nanocrystals in monodisperse silica with high biocompatibility. Chemical Engineering Journal. Available at: https://www.sciencedirect.com/science/article/abs/pii/S1385894721056849

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