Laser-driven synthesis of nanoparticles for therapeutic applications

Abstract

Recent advancement in medicine, technology and science require implementation of nanotechnology for which nanoparticles (NP) are of interest. Important medical applications utilise NP for therapeutics such as photothermal agents and targeted drug delivery. Conventional NP production such as chemical reduction can synthesise gold nanoparticle (AuNP) colloidal solutions, however such products are expensive and contain impurities. This research investigates the synthesis and development of laser ablation in liquids as a cost effective and universal method of synthesising several species of ultra-pure NP.
This experimental research performed NIR laser ablation of solid gold (Au) or titanium dioxide (TiO2) submerged in deionised water to produce a colloidal solution of AuNP or titanium dioxide nanoparticles (TiO2NP). Ultra-fast lasers with laser fluences ranging from 24-190 J/cm2 ablated Au to produce a colloidal solution of AuNP. A nanosecond (ns) laser performed similar experiments using fluences in the range of 1.2-15 kJ/cm2 producing AuNP and TiO2NP. Cytotoxicity tests were performed with both species of NP up to concentrations of 40 µg/ml which were synthesised via ns laser ablation. Tests were performed on L929 fibroblast, RAW 264.7 macrophages, and antibacterial tests with S. aureus and E. coli bacteria.
The ultra-fast laser demonstrated good size controllability of nanoparticles with modal diameters ranging from 5-8 nm depending on laser fluence, with Gaussian size distributions <0.3 Polydispersity index (PDI). At fluences > 90 J/cm2, a second peak emerging from the size distribution at 10-15 nm. The concentration was estimated around 68-84 µg/ml and zeta-potential (ζ) measured to be -22.2±0.4 mV. Synthesis with the ns laser of AuNP and TiO2NP gave TEM modal diameters at 8 nm and 13 nm, and hydrodynamic diameters around 130 nm and 370 nm respectively, with <0.3 PDI, and ζ around -20 mV. UV-Vis spectroscopy estimated AuNP diameters of 3.6 nm-9 nm. Cytotoxicity tests on L929 fibroblasts proved AuNP cyto-compatibility, and TiO2NP were cytotoxic above 35 µg/ml but cyto-compatible for RAW 264.7 macrophages. Anti-bacterial tests with AuNP had a 3 log reduction with increasing concentration and TiO2NP showed a 3-4 log reduction of CFU/ml from 5-40 µg/ml. Furthermore, a comparative study with commercially produced TiO2NP showed laser synthesised NP with stronger anti-bacterial properties.
Synthesis of NP through laser ablation can reliably produce NP with narrow size distributions and good size controllability was found with ultra-fast laser. ζ around ±20 mV demonstrates a stable solution contrary to coagulation evidence. The cyto-compatibility, particularly AuNP, show promise for implementation into clinical applications. Future work into NP laser synthesis of other nano-shapes, species, and functionalisation will push this research further.

Date of Award	Dec 2022
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Gianluca Sarri (Supervisor), David Riley (Supervisor) & Chi Wai Chan (Supervisor)