Nanoparticle-Based Therapies of Skin and Lung Cancers with Laser Hyperthermia and Photodynamic Therapy

Abstract

Nanoparticle-based therapies have emerged as a promising approach in oncology, offering innovative solutions for enhancing cancer treatment. This study explores advanced nanoparticle technologies integrating laser hyperthermia, targeted drug delivery, and photodynamic therapy (PDT) to improve therapeutic outcomes.  By combining these modalities, nanoparticle-based therapies hold the potential to revolutionize cancer treatment, offering enhanced efficacy, reduced side effects, and improved patient outcomes.

Firstly, the study focuses on the intricate heat transport dynamics associated with laser hyperthermia therapy for skin cancer. Two laser beams different in shape with a wavelength of 980 nm in the near-infrared (NIR) range were used to study temperature changes inside tumours using Pennes’ bioheat transfer equation. The investigation focuses on the utilisation of Ytterbium nanoparticles (Yb NPs), which are selected for their distinct optical characteristics. These include a significant absorption cross-section at wavelengths of about 980 nm and a simple two-energy level system. Theoretical analysis demonstrates that the use of YbNPs greatly improves the efficiency of heat generation. Using a Gaussian laser beam shape, YbNPs generate a maximum temperature increase of 5°C inside the tumour, while a flat-top beam shape leads to a 3°C rise. These temperature increases are in comparison to cases where nanoparticles are not present. The results emphasise the capability of YbNPs to enhance the accuracy and effectiveness of laser hyperthermia in the treatment of skin cancer.

This study expanded the experimental part by incorporating YbNPs into synthesising upconversion nanoparticles (UCNPs) for targeted drug delivery and PDT in lung cancer treatment. UCNPs were synthesized via a Polyol method and surface-modified with polyethylene glycol (PEG) to enhance biocompatibility. Further functionalization with folic acid (FA) facilitated targeted delivery to MRC-5 (normal) and A549 (lung cancer) cell lines. The UCNPs were loaded with the chemotherapeutic drug paclitaxel (PTX), which inhibits microtubule polymerization, forming UCNPs-PEG-FA-PTX complexes. Furthermore, tetraphenylporphyrin (TPP), a dye used as a photosensitizer, was incorporated into the study to facilitate PDT. Transmission Electron Microscopy (TEM) characterization revealed nanoparticles with an average size of 22.5 ± 8.67 nm, exhibiting arbitrary shapes and a degree of variability in size and morphology. Zeta potential analysis confirmed a shift from +24.5 mV for UCNPs to -14 mV for UCNPs-PEG-FA/PVA-PTX, indicating successful drug loading and surface modification. Dynamic Light Scattering (DLS) showed a larger particle size for drug-loaded UCNPs, with a mean diameter of 117 nm. Cell viability and apoptosis were evaluated using MTT and Flow cytometry assays. The UCNPs-PEG-FA/PVA-PTX complex demonstrated a significantly reduced A549 cell viability, with an IC50 of 11.15 µg/ml at 72 hours, compared to 22.8 µg/ml in MRC-5 cells, and increased apoptosis in cancer cells more than in normal cells. Importantly, the combination of laser treatment (980 nm) and drug delivery demonstrated the most pronounced effect, reducing cancer cell viability with minimal impact on normal cells. In contrast, UCNPs-PEG-FA and UCNPs exhibited minimal cytotoxicity, underscoring their biocompatibility. This study examines nanoparticle-based treatments, highlights their potential applications, and establishes a robust foundation for future investigations in this promising field. The results contribute to the expanding understanding of cancer treatment and offer significant insights for future studies.

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