Encapsulated Rose Bengal Enhances the Photodynamic Treatment of Triple-Negative Breast Cancer Cells.

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

Rose bengal-encapsulated chitosan nanoparticles for the photodynamic treatment of Trichophyton species.

Rose bengal (RB) solutions coupled with a green laser have proven to be efficient in clearing resilient nail infections caused by Trichophyton rubrum in a human pilot study and in extensive in vitro experiments. Nonetheless, the RB solution can become diluted or dispersed over the tissue and prevented from penetrating the nail plate to reach the subungual area where fungal infection proliferates. Nanoparticles carrying RB can mitigate the problem of dilution and are reported to effectively penetrate through the nail. For this reason, we have synthesized RB-encapsulated chitosan nanoparticles with a peak distribution size of ~200 nm and high reactive oxygen species (ROS) production. The RB-encapsulated chitosan nanoparticles aPDT were shown to kill more than 99% of T. rubrum, T. mentagrophytes, and T. interdigitale spores, which are the common clinically relevant pathogens in onychomycosis. These nanoparticles are not cytotoxic against human fibroblasts, which promotes their safe application in clinical translation.

Photodynamic Treatment of Human Breast and Prostate Cancer Cells Using Rose Bengal-Encapsulated Nanoparticles.

Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94-98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 µg/mL RB-nanoparticles, fluence ~126 J/cm2, and irradiance ~0.21 W/cm2). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications.

Fabrication and characterization of chitosan nanoparticles using the coffee-ring effect for photodynamic therapy.

BACKGROUND AND OBJECTIVES: Biocompatible nanoparticles have been increasingly used in a variety of medical applications, including photodynamic therapy. Although the impact of synthesis parameters and purification methods is reported in previous studies, it is still challenging to produce a reliable protocol for the fabrication, purification, and characterization of nanoparticles in the 200-300 nm range that are highly monodisperse for biomedical applications. STUDY DESIGN/MATERIALS AND METHODS: We investigated the synthesis of chitosan nanoparticles in the 200-300 nm range by evaluating the chitosan to sodium tripolyphosphate (TPP) mass ratio and acetic acid concentration of the chitosan solution. Chitosan nanoparticles were also crosslinked to rose bengal and incubated with human breast cancer cells (MCF-7) to test photodynamic activity using a green laser (λ = 532 nm, power = 90 mW). RESULTS: We established a simple protocol to fabricate and purify biocompatible nanoparticles with the most frequent size occurring between 200 and 300 nm. This was achieved using a chitosan to TPP mass ratio of 5:1 in 1% v/v acetic acid at a pH of 5.5. The protocol involved the formation of nanoparticle coffee rings that showed the particle shape to be spherical in the first approximation. Photodynamic treatment with rose bengal-nanoparticles killed ~98% of cancer cells. CONCLUSION: A simple protocol was established to prepare and purify spherical and biocompatible chitosan nanoparticles with a peak size of ~200 nm. These have remarkable antitumor activity when coupled with photodynamic treatment.

Effective photodynamic treatment of Trichophyton species with Rose Bengal.

Photodynamic therapy (PDT) with Rose Bengal has previously achieved eradication of Trichophyton rubrum infections causing toenail onychomycosis; however, its antifungal activity against other clinically relevant dermatophytes has yet to be studied. Here, we test the efficacy of PDT using Rose Bengal (140 µM) and 532 nm irradiation (101 J/cm2 ) against Trichophyton mentagrophytes and Trichophyton interdigitale spores, in comparison to T. rubrum. A significant reduction (>99%) of T. mentagrophytes and T. interdigitale was observed, while actual eradication of viable T. rubrum was achieved (99.99%). Laser irradiation alone inhibited growth of T. rubrum (55.2%) and T. mentagrophytes (45.2%) significantly more than T. interdigitale (25.5%) (P = .0086), which may indicate an increased presence of fungal pigments, xanthomegnin and melanin. The findings suggest that Rose Bengal-PDT can act against a broader spectrum of fungal pathogens, and with continued development may be employed in a wider range of clinical antifungal applications.

Photodynamic therapy with nanoparticles to combat microbial infection and resistance.

Infections caused by drug-resistant pathogens are rapidly increasing in incidence and pose an urgent global health concern. New treatments are needed to address this critical situation while preventing further resistance acquired by the pathogens. One promising approach is antimicrobial photodynamic therapy (PDT), a technique that selectively damages pathogenic cells through reactive oxygen species (ROS) that have been deliberately produced by light-activated chemical reactions via a photosensitiser. There are currently some limitations to its wider deployment, including aggregation, hydrophobicity, and sub-optimal penetration capabilities of the photosensitiser, all of which decrease the production of ROS and lead to reduced therapeutic performance. In combination with nanoparticles, however, these challenges may be overcome. Their small size, functionalisable structure, and large contact surface allow a high degree of internalization by cellular membranes and tissue barriers. In this review, we first summarise the mechanism of PDT action and the interaction between nanoparticles and the cell membrane. We then introduce the categorisation of nanoparticles in PDT, acting as nanocarriers, photosensitising molecules, and transducers, in which we highlight their use against a range of bacterial and fungal pathogens. We also compare the antimicrobial efficiency of nanoparticles to unbound photosensitisers and examine the relevant safety considerations. Finally, we discuss the use of nanoparticulate drug delivery systems in clinical applications of antimicrobial PDT.