Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells.

Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.

Electron-Withdrawing Substituents Enhance the Type I PDT and NIR-II Fluorescence of BODIPY J Aggregates for Bioimaging and Cancer Therapy.

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.

The Latest Look at PDT and Immune Checkpoints.

Photodynamic therapy (PDT) can not only directly eliminate cancer cells, but can also stimulate antitumor immune responses. It also affects the expression of immune checkpoints. The purpose of this review is to collect, analyze, and summarize recent news about PDT and immune checkpoints, along with their inhibitors, and to identify future research directions that may enhance the effectiveness of this approach. A search for research articles published between January 2023 and March 2024 was conducted in PubMed/MEDLINE. Eligibility criteria were as follows: (1) papers describing PDT and immune checkpoints, (2) only original research papers, (3) only papers describing new reports in the field of PDT and immune checkpoints, and (4) both in vitro and in vivo papers. Exclusion criteria included (1) papers written in a language other than Polish or English, (2) review papers, and (3) papers published before January 2023. 24 papers describing new data on PDT and immune checkpoints have been published since January 2023. These included information on the effects of PDT on immune checkpoints, and attempts to associate PDT with ICI and with other molecules to modulate immune checkpoints, improve the immunosuppressive environment of the tumor, and resolve PDT-related problems. They also focused on the development of new nanoparticles that can improve the delivery of photosensitizers and drugs selectively to the tumor. The effect of PDT on the level of immune checkpoints and the associated activity of the immune system has not been fully elucidated further, and reports in this area are divergent, indicating the complexity of the interaction between PDT and the immune system. PDT-based strategies have been shown to have a beneficial effect on the delivery of ICI to the tumor. The utility of PDT in enhancing the induction of the antitumor response by participating in the triggering of immunogenic cell death, the exposure of tumor antigens, and the release of various alarm signals that together promote the activation of dendritic cells and other components of the immune system has also been demonstrated, with the result that PDT can enhance the antitumor immune response induced by ICI therapy. PDT also enables multifaceted regulation of the tumor's immunosuppressive environment, as a result of which ICI therapy has the potential to achieve better antitumor efficacy. The current review has presented evidence of PDT's ability to modulate the level of immune checkpoints and the effectiveness of the association of PDT with ICIs and other molecules in inducing an effective immune response against cancer cells. However, these studies are at an early stage and many more observations need to be made to confirm their efficacy. The new research directions indicated may contribute to the development of further strategies.

Ruthenium complexes bearing nile red chromophore and one of its derivative: Theoretical evaluation of PDT-related properties.

The outcomes of DFT-based calculations are here reported to assess the applicability of two synthesized polypyridyl Ru(II) complexes, bearing ethynyl nile red (NR) on a bpy ligand, and two analogues, bearing modified-NR, in photodynamic therapy. The absorption spectra, together with the non-radiative rate constants for the S1 - Tn intersystem crossing transitions, have been computed for this purpose. Calculations evidence that the structural modification on the chromophore destabilizes the HOMO of the complexes thus reducing the H-L gap and, consequently, red shifting the maximum absorption wavelength within the therapeutic window, up to 620 nm. Moreover, the favored ISC process from the bright state involves the triplet state closest in energy, which is also characterized by the highest SOC value and by the involvement of the whole bpy ligand bearing the chromophore in delocalising the unpaired electrons. These outcomes show that the photophysical behavior of the complexes is dominated by the chromophore.

Mucus-Penetrating Nanoassembly as Potential Oral Phototherapeutic Formulation against Multi-Drug Resistant Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.

RSS and ROS Sequentially Activated Carbon Monoxide Release for Boosting NIR Imaging-Guided On-Demand Photodynamic Therapy.

Carbon monoxide shows great therapeutic potential in anti-cancer. In particular, the construction of multifunctional CO delivery systems can promote the precise delivery of CO and achieve ideal therapeutic effects, but there are still great challenges in design. In this work, a RSS and ROS sequentially activated CO delivery system is developed for boosting NIR imaging-guided on-demand photodynamic therapy. This designed system is composed of a CO releaser (BOD-CO) and a photosensitizer (BOD-I). BOD-CO can be specifically activated by hydrogen sulfide with simultaneous release of CO donor and NIR fluorescence that can identify H2S-rich tumors and guide light therapy, also depleting H2S in the process. Moreover, BOD-I generates 1O2 under long-wavelength light irradiation, enabling both PDT and precise local release of CO via a photooxidation mechanism. Such sequential activation of CO release by RSS and ROS ensured the safety and controllability of CO delivery, and effectively avoided leakage during delivery. Importantly, cytotoxicity and in vivo studies reveal that the release of CO combined with the depletion of endogenous H2S amplified PDT, achieving ideal anticancer results. It is believed that such theranostic nanoplatform can provide a novel strategy for the precise CO delivery and combined therapy involved in gas therapy and PDT.

Self-Oxygenated Hydrogel Enhances Immune Cell Response and Infiltration Via Triggering Dual DNA Damage to Activate cGAS-STING and Inhibiting CAFs.

Immune checkpoint inhibitors (ICIs) offer promise in breaking through the treatment and survival dilemma of triple-negative breast cancer (TNBC), yet only immunomodulatory subtype and ≈5% TNBC patients respond as monotherapy due to lack of effector immune cells (internal problem) and physical barrier (external limitation) formed by cancer-associated fibroblasts (CAFs). A hydrogel drug-delivery platform, ALG@TBP-2/Pt(0)/nintedanib (ALG@TPN), is designed to induce strong immune functions and the dual elimination of the internal and external tumor microenvironment (TME). Activated by white light, through type I and II photodynamic therapy (PDT), TBP-2 generates large amounts of reactive oxygen species (ROS) intracellularly, oxidizing mitochondrial DNA (mtDNA). The unique catalase activity of Pt(0) converts endogenous H2O2 to O2, reducing the anoxia-limiting PDT and enhancing ROS generation efficacy. Abundant ROS can oxidize Pt(0) to cytotoxic Pt(II), damaging the nuclear DNA (nDNA). Dual damage to mtDNA and nDNA might bi-directionally activate the cGAS/STING pathway and enhance the immune cell response. Besides, nintedanib demonstrates a significant inhibitory effect on CAFs, weakening the immune barrier and deepening immune cell infiltration. Overall, the study provides a self-oxygenating hydrogel with the "PDT/chemotherapy/anti-CAFs" effect, triggering the cGAS/STING pathway to reshape the TME. Both internal and external interventions increase anti-TNBC immune responses.

Catalytic and selective red light-triggered photodegradation of a G-quadruplex DNA by a zinc (II) phthalocyanine.

Water-soluble phthalocyanine (Pc) derivatives have been regarded as potential G-quadruplex (G4) nucleic acid-targeting ligands for anticancer therapy and have been extensively studied as effective photosensitizers for photodynamic therapy (PDT). Understanding how photosensitizers interact with nucleic acids and the subsequent photolytic reactions is essential for deciphering the initial steps of PDT, thereby aiding in the development of new photosensitizing agents. In this study, we found that red-light irradiation of a mixture of a Zn(II) Pc derivative and an all-parallel G4 DNA leads to catalytic and selective photodegradation of the DNA by reactive oxygen species (ROS) generated from the Zn(II) Pc derivative bound to DNA through a reaction mechanism similar to that of an enzyme reaction. This finding provides a novel insight into the molecular design of a photosensitizer to enhance its PDT efficacy.

Phototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killing.

Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes showed intense emission with long lifetimes of the excited state. Femtosecond transient absorption experiments established the nature of the lowest excited state as 3IL state. Singlet oxygen generation with good yields (40% for 1 and 82% for 2) was established by detecting 1O2 directly, through its emission at 1270 nm. Photostability studies were also performed to assess the viability of the complexes as photosensitizers (PS) for photodynamic therapy (PDT). Complex 1 was selected as a good candidate to investigate light-activated killing of cells, whilst complex 2 was found to be toxic in the dark and unstable under light. Complex 1 demonstrated high phototoxicity indexes (PI) in the visible region, PI > 250 after irradiation at 405 nm and PI > 150 at 455 nm, in EJ bladder cancer cells.

Application of Mono and Trinuclear Cyclometalated Iridium (III) Complexes in Differential Bacterial Imaging and Antimicrobial Photodynamic Therapy.

The application of transition metal complexes for antimicrobial photodynamic therapy (PDT) has emerged as an attractive alternative in mitigating a broad range of bacterial pathogens, including multidrug-resistant pathogens. In view of their photostability, long excited-state lifetimes, and tunable emission properties, transition metal complexes also contribute as bioimaging agents. In the present work, we designed mono and trinuclear cyclometalated iridium (III) complexes to explore their imaging application and antibacterial potential. For this, we used Methicillin-resistant S. aureus (MRSA), the most prevalent of community-associated (CA) multidrug-resistant (MDR) bacteria (CA MDR) and Lactococcus lactis (L. lactis) as Gram-positive while Campylobacter jejuni (C. jejuni) and E. coli as Gram-negative bacteria. In addition to differential bioimaging of these bacteria, we assessed the antibacterial effects of both mono and trinuclear Ir(III) complexes under exposure to 427 nm LED light. The data presented herein strongly suggest better efficacy of trinuclear Ir(III) complex over the mononuclear complex in imparting photoinduced cell death of MRSA. Based on the safety profile of these complexes, we propose that trinuclear cyclometalated iridium(III) complex holds great promise for selective recognition and targeting MDR bacteria with minimal off-target effect.

Hypericin-mediated photodynamic therapy inhibits metastasis and EMT of colorectal cancer cells by regulating RhoA-ROCK1 signaling pathway.

Colorectal cancer (CRC) is significantly contributed to global cancer mortality rates. Treating CRC is particularly challenging due to metastasis and drug resistance. There is a pressing need for new treatment strategies against metastatic CRC. Photodynamic therapy (PDT) offers a well-established, minimally invasive treatment option for cancer with limited side effects. Hypericin (HYP), a potent photosensitizer for PDT, has been documented to induce cytotoxicity and apoptosis in various types of cancers. However, there are few reports on the inhibitory effects of HYP-mediated PDT on the metastatic ability of CRC cells. Here, we evaluate the inhibitory effects of HYP-mediated PDT against metastatic CRC cells and define its underlying mechanisms. Wound-healing and Transwell assays show that HYP-mediated PDT suppresses migration and invasion of CRC cells. F-actin visualization assays indicate HYP-mediated PDT decreases F-actin formation in CRC cells. TEM assays reveal HYP-mediated PDT disrupts pseudopodia formation of CRC cells. Mechanistically, immunofluorescence and western blotting results show that HYP-mediated PDT upregulates E-cadherin and downregulates N-cadherin and Vimentin. HYP-mediated PDT also suppresses key EMT regulators, including Snail, MMP9, ZEB1 and α-SMA. Additionally, the expressions of RhoA and ROCK1 are downregulated by HYP-mediated PDT. Together, these findings suggest that HYP-mediated PDT inhibits the migration and invasion of HCT116 and SW620 cells by modulating EMT and RhoA-ROCK1 signaling pathway. Thus, HYP-mediated PDT presents a potential therapeutic option for CRC.

Compounding Methylene Blue with Selenium-decorated Graphene Quantum Dots to Improve Singlet Oxygen Production for Photodynamic Therapy Application.

Graphene quantum dots (GQDs) are known as suitable material to be applied in different fields such as photodynamic therapy (PDT). Herein, GQDs were synthesized by the pyrolysis method and then decorated with selenium (Se). Afterward, they were combined with methylene blue (MB) to increase singlet oxygen generation as well as to apply them more effectively in the PDT method. Furthermore, GQDs were investigated by transmission electron microscope (TEM), photoluminescence spectrum (PL), Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscope (FESEM), reactive oxygen species (ROS) measurement, and cytotoxicity measurement. GQDs showed no dependence on the excitation wavelength. The result of ROS measurement proves that the combination of GQD-Se and MB increases singlet oxygen production. Moreover, afterglow measurement approved the beneficial effect of GQD-Se on even deep and near skin tumor treatment. Cytotoxicity measurements under dark conditions, cell viability, and the side effects on human cells were determined by (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay. Our findings show that under dark conditions, even high concentrations of nanoparticles have no significant effect on cell viability. These findings and the high biocompatibility of GQDs indicate the effective application of GQD-Se-MB in PDT.

Facile synthesis of Gd/Ru-doped fluorescent carbon dots for fluorescent/MR bimodal imaging and tumor therapy.

Functional metal doping endows fluorescent carbon dots with richer physical and chemical properties, greatly expanding their potential in the biomedical field. Nonetheless, fabricating carbon dots with integrated functionality for diagnostic and therapeutic modalities remains challenging. Herein, we develop a simple strategy to prepare Gd/Ru bimetallic doped fluorescent carbon dots (Gd/Ru-CDs) via a one-step microwave-assisted method with Ru(dcbpy)3Cl2, citric acid, polyethyleneimine, and GdCl3 as precursors. Multiple techniques were employed to characterize the morphology and properties of the obtained carbon dots. The Gd/Ru-CDs are high mono-dispersity, uniform spherical nanoparticles with an average diameter of 4.2 nm. Moreover, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) confirmed the composition and surface properties of the carbon dots. In particular, the successful doping of Gd/Ru enables the carbon dots not only show considerable magnetic resonance imaging (MRI) performance but also obtain better fluorescence (FL) properties, especially in the red emission area. More impressively, it has low cytotoxicity, excellent biocompatibility, and efficient reactive oxygen species (ROS) generation ability, making it an effective imaging-guided tumor treatment reagent. In vivo experiments have revealed that Gd/Ru-CDs can achieve light-induced tumor suppression and non-invasive fluorescence/magnetic resonance bimodal imaging reagents to monitor the treatment process of mouse tumor models. Thus, this simple and efficient carbon dot manufacturing strategy by doping functional metals has expanded avenues for the development and application of multifunctional all-in-one theranostics.

Comparative efficacy of brolucizumab, half-dose photodynamic therapy, and aflibercept in managing chronic central serous chorioretinopathy.

PURPOSE: To compare the efficacy of brolucizumab, half-dose PDT, and aflibercept in treating chronic central serous chorioretinopathy (CSC). METHODS: A retrospective cohort study with chronic CSC patients who underwent intravitreal injection of one shot of brolucizumab or aflibercept in the first 3 months, followed by pro re nata regimens or a single session of half-dose PDT, was retrospectively reviewed. The primary outcome measure was the proportion of eyes that achieved complete absorption of retinal fluid without requiring any rescue treatment. Secondary outcomes included changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and central choroidal thickness (CCT). RESULTS: A total of 54 consecutive patients were included in this study with 18 patients in each group. At months 1 and 2, the brolucizumab group exhibited the highest rate of complete retinal fluid resolution (61% and 77%), followed by the half-dose PDT group (56% and 72%), and lowest in the aflibercept group (28% and 33%), with statistically significant differences noted at month 2 (P = 0.012). The brolucizumab group also demonstrated the most significant reduction in CCT at months 1 and 2 among the three groups (P = 0.007 and 0.001). Recurrence of retinal fluid in the brolucizumab groups was predominantly observed at month 3. Conversely, the half-dose PDT group exhibited the most favorable anatomical results starting from month 3. Notably, mild vitritis was observed in one case from the brolucizumab group. CONCLUSIONS: Single injection of brolucizumab demonstrates trends of faster regression of persistent residual retinal fluid, greater CCT and CRT decline, and matched BCVA compared to half-dose PDT in the short term.

Effect of photodynamic therapy with 5-aminolevulinic acid and EDTA-2Na against mixed infection of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa.

BACKGROUND: The increasing abundance of drug-resistant bacteria is a global threat. Photodynamic therapy is an entirely new, non-invasive method for treating infections caused by antibiotic-resistant strains. We previously described the bactericidal effect of photodynamic therapy on infections caused by a single type of bacterium. We showed that gram-positive and gram-negative bacteria could be killed with 5-aminolevulic acid and 410 nm light, respectively. However, clinically, mixed infections are common and difficult to treat. OBJECTIVE: We investigated the bactericidal effects of photodynamic therapy on mixed infections of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. METHODS: We compared bacterial growth with and without photodynamic therapy in vitro. Then, in vivo, we studied mixed infections in a mouse skin ulcer model. We evaluated the rates of ulcer area reduction and transitions to healing in treated and untreated mice. In addition, a comparison was made between PDT and existing topical drugs. RESULTS: We found that photodynamic therapy markedly reduced the growth of both methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, in culture, and it reduced the skin ulcer areas in mice. PDT was also more effective than existing topical medicines. CONCLUSION: This study showed that photodynamic therapy had antibacterial effects against a mixed infection of gram-positive and gram-negative bacteria, and it promoted skin ulcer healing. These results suggested that photodynamic therapy could be effective in both single- and mixed-bacterial infections.

Hallmarks of anticancer and antimicrobial activities of corroles.

Corroles provide a remarkable opportunity for the development of cancer theranostic agents among other porphyrinoids. While most transition metal corrole complexes are only therapeutic, post-transition metallocorroles also find their applications in bioimaging. Moreover, corroles exhibit excellent photo-physicochemical properties, which can be harnessed for antitumor and antimicrobial interventions. Nevertheless, these intriguing, yet distinct properties of corroles, have not attained sufficient momentum in cancer research. The current review provides a comprehensive summary of various cancer-relevant features of corroles ranging from their structural and photophysical properties, chelation, protein/corrole interactions, to DNA intercalation. Another aspect of the paper deals with the studies of corroles conducted in vitro and in vivo with an emphasis on medical imaging (optical and magnetic resonance), photo/sonodynamic therapies, and photodynamic inactivation. Special attention is also given to a most recent finding that shows the development of pH-responsive phosphorus corrole as a potent antitumor drug for organelle selective antitumor cytotoxicity in preclinical studies. Another biomedical application of corroles is also highlighted, signifying the application of water-soluble and completely lipophilic corroles in the photodynamic inactivation of microorganisms. We strongly believe that future studies will offer a greater possibility of utilizing advanced corroles for selective tumor targeting and antitumor cytotoxicity. In the line with future developments, an ideal pipeline is envisioned on grounds of cancer targeting nanoparticle systems upon decoration with tumor-specific ligands. Hence, we envision that a bright future lies ahead of corrole anticancer research and therapeutics.

Molecular effects of photodynamic therapy with curcumin on Leishmania major promastigotes.

Leishmaniasis is a neglected disease mainly affecting low-income populations. Conventional treatment involves several side effects, is expensive, and, in addition, protozoa can develop resistance. Photodynamic therapy (PDT) is a promising alternative in treating the disease. PDT involves applying light at a specific wavelength to activate a photosensitive compound (photosensitizer, PS), to produce reactive oxygen species (ROS). Curcumin and its photochemical characteristics make it a good candidate for photodynamic therapy. Studies evaluating gene expression can help to understand the molecular events involved in the cell death caused by PDT. In the present study, RNA was extracted from promastigotes from the control and treated groups after applying PDT. RT-qPCR was performed to verify the expression of the putative ATPase beta subunit (ATPS), ATP synthase subunit A (F0F1), argininosuccinate synthase 1 (ASS), ATP-binding cassette subfamily G member 2 (ABCG2), glycoprotein 63 (GP63), superoxide dismutase (FeSODA), and glucose-6-phosphate dehydrogenase (G6PDH) genes (QR). The results suggest that PDT altered the expression of genes that participate in oxidative stress and cell death pathways, such as ATPS, FeSODA, and G6PD. The ATP-F0F1, ASS, and GP63 genes did not have their expression altered. However, it is essential to highlight that other genes may be involved in the molecular mechanisms of oxidative stress and, consequently, in the death of parasites.

A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy.

Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.

Topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) for lichen sclerosus of face: case report and literature review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis typical of the genital region, with rare involvement of extragenital areas and particularly the face. LS therapeutic management is challenging, and common therapies including topical and systemic corticosteroids, topical calcineurin inhibitors, surgery are often ineffective. Herein, we present a case of LS occurred in a 36-year-old girl with facial involvement resistant to therapy with systemic corticosteroids and topical tacrolimus. Considering the involvement of a sensitive area, the young age of the patient, and the consistent clinical experience in using photodynamic therapy for the treatment of facial skin disease, we started a treatment with topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) with a dosage of 37 J/cm2 once a month. We compared our case with eight other facial LS patients from the literature and treated differently.

Dual-targeting liposomes modified with BTP-7 and pHA for combined delivery of TCPP and TMZ to enhance the anti-tumour effect in glioblastoma cells.

AIM: To construct a novel nano-carrier with dual ligands to achieve superior anti-tumour efficacy and lower toxic side effects. METHODS: Liposomes were prepared by thin film hydration method. Ultraviolet, high performance liquid chromatography, nano-size analyser, ultrafiltration centrifugation, dialysis, transmission electron microscope, flow cytometry, Cell Counting Kit-8, confocal laser scanning microscopy, transwell, and tumorsphere assay were used to study the characterisations, cytotoxicity, and in vitro targeting of dg-Bcan targeting peptide (BTP-7)/pHA-temozolomide (TMZ)/tetra(4-carboxyphenyl)porphyrin (TCPP)-Lip. RESULTS: BTP-7/pHA-TMZ/TCPP-Lip was a spheroid with a mean diameters of 143 ± 3.214 nm, a polydispersity index of 0.203 ± 0.025 and a surface charge of -22.8 ± 0.425 mV. The drug loadings (TMZ and TCPP) are 7.40 ± 0.23% and 2.05 ± 0.03% (mg/mg); and the encapsulation efficiencies are 81.43 ± 0.51% and 84.28 ± 1.64% (mg/mg). The results showed that BTP-7/pHA-TMZ/TCPP-Lip presented enhanced targeting and cytotoxicity. CONCLUSION: BTP-7/pHA-TMZ/TCPP-Lip can specifically target the tumour cells to achieve efficient drug delivery, and improve the anti-tumour efficacy and reduces the systemic toxicity.