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.

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.

A One Step Procedure toward Conductive Suspensions of Liposome-Polyaniline Complexes.

Interaction of conjugated polymers with liposomes is an attractive approach that benefits from both systems' characteristics such as electroactivity and enhanced interaction with cells. Conjugated polymer-liposome complexes have been investigated for bioimaging, drug delivery, and photothermal therapy. Their fabrication has largely been achieved by multistep procedures that require first the synthesis and processing of the conjugated polymer. Here, a new one step fabrication approach is reported based on in situ polymerization of a conjugated monomer precursor around liposomes. Polyaniline (PANI) doped with phytic acid is synthesized via oxidative polymerization in the presence of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) vesicles to produce a conductive aqueous suspension of Liposome-PANI complexes. PANI interacts with liposomes without disrupting the bilayer as shown using differential scanning calorimetry and fluorescence quenching studies of the hydrophobic Nile red probe. The electronic conductivity of the Liposome-PANI complexes, which stems from the doped PANI accessible on the liposome surface, is confirmed using conductive atomic force microscopy and electrochemical impedance spectroscopy. Further, short-term in vitro cell studies show that the complexes colocalize with the cell membrane without reducing cell proliferation. This study presents a novel fabrication route to conductive suspensions of conjugated polymer-liposome complexes suitable for potential applications at the biointerface.

Porous chitosan adhesives with L-DOPA for enhanced photochemical tissue bonding.

L-3,4-dihydroxyphenylalanine (L-DOPA) is a naturally occurring catechol that is known to increase the adhesive strength of various materials used for tissue repair. With the aim of fortifying a porous and erodible chitosan-based adhesive film, L-DOPA was incorporated in its fabrication for stronger photochemical tissue bonding (PTB), a repair technique that uses light and a photosensitiser to promote tissue adhesion. The results showed that L-DOPA did indeed increase the tissue bonding strength of the films when photoactivated by a green LED, with a maximum strength recorded of approximately 30 kPa, 1.4 times higher than in its absence. The addition of L-DOPA also did not appreciably change the swelling, mechanical and erodible properties of the film. This study showed that strong, porous and erodible adhesive films for PTB made from biocompatible materials can be obtained through a simple inclusion of a natural additive such as L-DOPA, which was simply mixed with chitosan without any chemical modifications. In vitro studies using human fibroblasts showed no negative effect on cell proliferation indicating that these films are biocompatible. The films are convenient for various surgical applications as they can provide strong tissue support and a microporous environment for cellular infusion without the use of sutures. STATEMENT OF SIGNIFICANCE: Tissue adhesives are not as strong as sutures on wounds under stress. Our group has previously demonstrated that strong sutureless tissue repair can be realised with chitosan-based adhesive films that photochemically bond to tissue when irradiated with green light. The advantage of this technique is that films are easier to handle than glues and sutures, and their crosslinking reactions can be controlled with light. However, these films are not optimal for high-tension tissue regenerative applications because of their non-porous structure, which cannot facilitate cell and nutrient exchange at the wound site. The present study resolves this issue, as we obtained a strong and porous photoactivated chitosan-based adhesive film, by simply using freeze drying and adding L-DOPA.

Porous Chitosan Films Support Stem Cells and Facilitate Sutureless Tissue Repair.

Photochemical tissue bonding with chitosan-based adhesive films is an experimental surgical technique that avoids the risk of thermal tissue injuries and the use of sutures to maintain strong tissue connection. This technique is advantageous over other tissue repair methods as it is minimally invasive and does not require mixing of multiple components before or during application. To expand the capability of the film to beyond just a tissue bonding device and promote tissue regeneration, in this study, we designed bioadhesive films that could also support stem cells. The films were modified with oligomeric chitosan to tune their erodibility and made porous through freeze-drying for better tissue integration. Of note, porous adhesive films (pore diameter ∼110 µm), with 10% of the chitosan being oligomeric, could retain similar tissue bonding strengths (13-15 kPa) to that of the nonporous chitosan-based adhesives used in previous studies when photoactivated. When tested in vitro, these films exhibited a mass loss of ∼20% after 7 days, swelling ratios of ∼270-300%, a percentage elongation of ∼90%, and both a tensile strength and Young's modulus of ∼1 MPa. The physical properties of the films were suitable for maintaining the viability and multipotency of bone-marrow-derived human mesenchymal stem cells over the duration of culture. Thus, these biocompatible, photoactivated porous, and erodible adhesive films show promise for applications in controlled cell delivery and regenerative medicine.