PLGA/PFC particles loaded with gold nanoparticles as dual contrast agents for photoacoustic and ultrasound imaging

Abstract

Phase-change contrast agents consisting of a perfluorocarbon (PFC) liquid core stabilized by a lipid, protein, or polymer shell have been proposed for a variety of clinical applications. Previous work has demonstrated that vaporization can be induced by laser irradiation through optical absorbers incorporated inside the droplet. In this study, Poly-lactide-coglycolic acid (PLGA) particles loaded with PFC liquid and silica-coated gold nanoparticles (GNPs) were developed and characterized using photoacoustic (PA) methods. Microsized PLGA particles were loaded with PFC liquid and GNPs (14, 35, 55nm each with a 20nm silica shell) using a double emulsion method. The PA signal intensity and optical vaporization threshold were investigated using a 375 MHz transducer and a focused 532-nm laser (up to 450-nJ per pulse). The laser-induced vaporization threshold energy decreased with increasing GNP size. The vaporization threshold was 850, 690 and 420 mJ/cm 2 for 5µm-sized PLGA particles loaded with 14, 35 and 55 nm GNPs, respectively. The PA signal intensity increased as the laser fluence increased prior to the vaporization event. This trend was observed for all particles sizes. PLGA particles were then incubated with MDA-MB-231 breast cancer cells for 6 hours to investigate passive targeting, and the vaporization of the PLGA particles that were internalized within cells. The PLGA particles passively internalized by MDA cells were visualized via confocal fluorescence imaging. Upon PLGA particle vaporization, bubbles formed inside the cells resulting in cell destruction. This work demonstrates that GNPs-loaded PLGA/PFC particles have potential as PA theranostic agents in PA imaging and optically-triggered drug delivery systems.

Design of triphasic poly(lactic-co-glycolic acid) nanoparticles containing a perfluorocarbon phase for biomedical applications

“…The main parameters, which affect the synthesis of PLGA particles are type and concentration of surfactant, concentration of polymer, and type of solvent for the organic phase (Scheme 1). 3,21,[24][25][26] Loading the particles with PFC alters the properties of miniemulsions, as PFCs form their own phase in solutions. Among different surfactants, polyvinyl alcohol (PVA) with low molecular weight (10 kDa) resulted in nanoparticles with a small hydrodynamic radius (R h ), and high PFCE loading.…”

Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

“…In this study, we used 50 nm gold nanospheres as the optical absorbing material due to their high absorption coefficient around 532 nm, and ease of synthesis [11] . A 20 nm silica coating was chosen to maximize the PA signal strength and the stability of gold nanospheres under laser irradiation [13].…”

“…PLGA particles containing PFH and silica coated GNPs with and without GNPs were prepared using a double emulsion solvent evaporation process [10] [11]. Briefly, PLGA polymer and DiD were dissolved in dichloromethane.…”

The Effect of Laser Power on Photothermoacoustic Imaging of Blood Containing Gold Nanoparticles and Deoxygenation using a Frequency-Domain Phased Array Probe: An In-vitro Assay

“…The medical imaging modality employed for detection of malignant tumors in organs such as breast cancer should provide high-specificity to cancer and high resolution for early In situ detection [18]. Since, the main strength of PAI is its ability to obtain functional, anatomical and molecular information in real-time with a high resolution at clinically relevant depths, therefore either endogenous biomolecules such as hemoglobin, melanin and carotonoids or exogenous contrast agents such as indocyanine green [19], nanoparticles [20,21], nanoshells [22,23], nanorods [24,25], nanocages [26,27], and nanodiamonds [28] can be employed for image enhancement. However, as it will be discussed, for in vivo applications the nanostructures must be active targeted by conjugating them with suitable moieties e.g., antibodies, peptides or folates to prevent from protein adsorption and aggregation.…”