Experimental and Numerical Investigation of Polydopamine Nanoparticles for Enhanced Photothermal Cancer Therapy

Abstract

Photothermal therapies are considered to be a safe and promising choice for small, localized superficial tumors.

During photothermal therapies, near-infrared light generates heat and selectively destroys the tumorous tissue.

However, achieving precise control over the tissue heating confined only to the localized zone remains a chal-

lenge. Any deviation from the intended heating can lead to over-ablation, resulting in significant damage to the

surrounding healthy tissue and critical structures, or under-ablation, which increases the chances of tumor recur-

rences. To overcome these challenges, administering nanoparticles within a target tumor has been proven to gen-

erate more precise heating and minimize damage to the surrounding healthy tissues, thereby increasing the overall

efficacy of the procedure. The use of metallic nanoparticles (e.g., silver, gold) to enhance photothermal effects

has received significant attention over the past decade. However, this approach introduces concerns regarding

material toxicity and patient risk. Polymer-based nanomaterials, with their biocompatible and biodegradable prop-

erties, offer a promising alternative to address these complications, warranting further exploration. This study

aims to investigate the potential of polymer-based nanoparticles composed of polydopamine (PDA) to enhance

the effectiveness of photothermal therapies for cancer treatment. PDA nanoparticles are melanin-like structures

synthesized through the oxidation of 3,4-dihydroxy-L-phenylalanine (DOPA) in an alkaline aqueous environment

with oxygen, and their size can be easily controlled by adjusting the solution’s pH. In this study, the influence of

various concentrations of spherical PDA nanoparticles (1000, 400, 200, 100, 50, and 25 μg/mL) was explored

through in vitro photothermal experiments. The temperature profile of the samples during 808 nm laser irradiation

with an intensity of 1.4 W/cm2 was captured with a thermal camera. A concentration-dependent relationship was

identified, and the highest PDA concentration of 1000 μg/mL led to the largest temperature change of 19.4 °C.

Furthermore, a finite element-based computational model was developed to quantify spatio-temporal thermal dy-

namics across different PDA nanoparticle concentrations. The absorption cross-sections of individual PDA nano-

particles were derived using Maxwell’s equations and extrapolated to different concentrations. The computational

absorption spectrum was compared to experimental data obtained using a spectrophotometer, highlighting rea-

sonable agreement. Beer-Lambert’s law was then applied to model the heat transfer within the nanoparticle sus-

pension utilizing a Gaussian laser profile across different concentrations. The model was validated against exper-

imental in vitro photothermal data of maximum attained temperature, and a parametric sensitivity analysis was

conducted to assess the impact of laser power and nanoparticle size on the efficacy of nanoparticle-assisted pho-

tothermal therapy. Both experimental and computational results highlight the significance of nanoparticle con-

centration, size, and laser power in improving the photothermal response of polymer-based nanoparticles. The

optimal nanoparticle parameters generating enhanced photothermal effects have also been identified based on

parametric sensitivity analysis. This study offers valuable insights into the future advancements and clinical trans-

lation of precision photothermal therapy, benefiting millions affected by cancer.