Combination Of Photodynamic Therapy Research Articles

Heavy-Atom-Free Nanoparticles Based on Boron Dipyrromethene Derivatives for Combined Photothermal and Photodynamic Cancer Therapy

Boron dipyrromethenes (BODIPYs) have been extensively studied in phototherapy against cancer. However, heavy-atom-free BODIPYs have been relatively less explored, and some of them are only used for photothermal therapy. Here, four heavy-atom-free BODIPYs with phenyl, naphthyl, anthracyl, or pyrenyl were synthesized and named B-mPh, B-mNa, B-mAn, and B-mPy, respectively. Stable nanoparticles (NPs) of the BODIPYs were prepared via the assembly with pluronic F127, which were named B-mPh NPs, B-mNa NPs, B-mAn NPs, and B-mPy NPs. The spin–orbit charge transfer (SOCT) of the anthracene group enhances the intersystem crossing (ISC) effect and improves the ability of B-mAn to generate singlet oxygen. Compared with other NPs, B-mAn NPs showed enhanced cytotoxicity upon irradiation. This kind of heavy-atom-free nanomaterials based on BODIPY, which promotes ISC by SOCT and enhances the generation of reactive oxygen species, plays an active part in the realization of combined photothermal and photodynamic therapy.

Cage-modified hypocrellin against multidrug-resistant Candida spp. with unprecedented activity in light-triggered combinational photodynamic therapy.

Infections caused by multidrug-resistant fungi pose a devastating threat to human health worldwide, making new antifungal strategies urgently desired. Antimicrobial photodynamic therapy (aPDT) has gained increasing attention due to its potential in fighting against fungal infection. However, the preparation of highly efficient and water-soluble photosensitizers (PSs) for this purpose remains a challenge. Herein, we present a new strategy to prepare powerful PSs for efficient aPDT by introducing a porous cage compound, which could facilitate the transportation of O2 and reactive oxygen species (ROS). Specifically, the natural PS hypocrellin A (HA) was attached to a novel organic cage compound (covalent organic polyhedra 1 tied, COP1T) with polyethylene glycol (PEG) chains to improve its water solubility. It was found that the resulting COP1T-HA exhibited in vitro antifungal efficiency several folds higher compared to the free HA in fighting against four types of multidrug-resistant fungal planktonic cells and biofilms, including the "super fungus" Candida auris. Interestingly, the red-shift of COP1T-HA adsorption led to the realization of phototheranostic aPDT for cage-modified HA or derivatives. Additionally, COP1T-HA exhibited good biocompatibility, excellent disinfection capacity and wound healing efficiency without obvious toxic effects in vivo of rat model. With further development and optimization, COP1T-HA has great potential to become a new class of antifungal agent to fight against drug-resistant pathogens.

A self-cascaded unimolecular prodrug for pH-responsive chemotherapy and tumor-detained photodynamic-immunotherapy of triple-negative breast cancer

Despite the success of immune checkpoint blockade (ICB) therapy in cancer management, ICB-based immunotherapy of triple-negative breast cancer (TNBC) still suffers from immunosuppressive tumor microenvironment (ITM). To break through the bottleneck of TNBC immunotherapy, a self-cascaded unimolecular prodrug consisting of an acidic pH-activatable doxorubicin and an aggregation-induced emission luminogen (AIEgen) photosensitizer coupled to a caspase-3-responsive peptide was engineered. The generated prodrug, could not only release doxorubicin initiatively in acidic tumor microenvironment, but also activate apoptosis-related caspase-3. The activated caspase-3 could in turn trigger release and in situ aggregation of photosensitizers. Importantly, the unimolecular prodrug exhibits a renal clearance pathway similar to small molecules in vivo, while the aggregated AIEgens prolong tumor retention for long-term fluorescence imaging and repeatable photodynamic therapy (PDT) by only one single-dose injection. Furthermore, the tumor-detained PDT boosts both immunogenic cell death of TNBC cells and maturation of dendritic cells. Finally, the combination of repeatable PDT with ICB therapy further promotes the proliferation and intratumoral infiltration of cytotoxic T lymphocytes, and effectively suppresses tumor growth and pulmonary metastasis. This prodrug is a proof-of-concept that confirms the first self-cascaded chemo-PDT strategy to reverse the ITM and boost the ICB-mediated TNBC immunotherapy.

297 Role of TGFβ1 in combination with N-acetyl cysteine in the response of squamous cell carcinoma to photodynamic therapy

In the present study, we aim to understand the implications of transforming growth factor β1 secreted by cancer-associated fibroblasts (CAFs) in the resistance of cutaneous squamous cell carcinoma (cSCC) cells to photodynamic therapy (PDT), as well as the effects of the combination of PDT with N-acetyl cysteine (NAC). PDT is widely used for the treatment of cSCC, and it involves the combination of visible light, molecular oxygen and a photoactive compound (photosensitizer), leading to cell death owing to the generation of reactive oxygen species.

Modern aspects of photodynamic therapy of basal cell skin cancer

Photodynamic therapy (PDT) is one of the most effective treatments for basal cell skin cancer (BCC). As the incidence rate of BCC is increasing worldwide, interest in developing new methods for diagnosing and treating this disease, taking into account long-term cosmetic results, is growing. The review article presents the results of domestic and foreign studies on the treatment of BCC with PDT. The presented results of studies from various domestic and foreign clinics indicate the high efficiency of independent PDT and a combination of PDT with other treatment methods. PDT is proposed to be used in combination with surgical methods and radiation therapy, immunomodulating and chemotherapeutic agents, and inhibitors of molecules involved in the carcinogenic process. These new strategies open the way to increasing the effectiveness of treatment and prevention of BCC. Moreover, in all studies, the safety of this non-invasive treatment, a low level of adverse reactions during therapy, good tolerance for the patient and excellent cosmetic treatment results are noted. The guidelines currently being developed in Europe and the United States provide consistent expert advice that reflects current published evidence of treatment outcomes for BCC using PDT. Moreover, the recommendations emphasize that the treatment plan for patients with “difficult to treat” BCC should be discussed at an interdisciplinary oncological council.

W18O49@EP nanoparticles improve the anti-tumor effect of radiotherapy and photodynamic therapy by avoiding the limitation of hypoxia.

Insufficient oxygen supply at the tumor site and hypoxia caused during tumor treatment lead to a poor therapeutic effect and poor prognosis. Therefore, effectively overcoming the problem of hypoxia in tumors and avoiding hypoxia that compromises the efficacy of the treatment could improve the anti-tumor therapeutic effect. Thus, this study reports the ability of W18O49@EP nanoparticles to release reactive oxygen species (ROS) during the combined tumor radiotherapy (RT) and photodynamic therapy (PDT). The release of ROS by the nanoparticles during near infrared light (NIR) irradiation was demonstrated by in vitro and in vivo experiments, realizing an effective PDT without inducing hypoxia. Indeed, the ROS did not derive from the oxygen in the tumor microenvironment but they were released by the nanoparticles. Thus, ROS could improve the therapeutic effect of RT avoiding the problem of hypoxia after RT. Hence, W18O49@EP nanoparticles greatly improved the anti-tumor effect due to their effectiveness despite the insufficient oxygen supply and hypoxia caused by traditional RT and PDT.

Multifunctional Mesoporous Hollow Cobalt Sulfide Nanoreactors for Synergistic Chemodynamic/Photodynamic/Photothermal Therapy with Enhanced Efficacy.

The unique tumor microenvironment (TME) characteristic of severe hypoxia, overexpressed intracellular glutathione (GSH), and elevated hydrogen peroxide (H2O2) concentration limit the anticancer effect by monotherapy. In this report, glucose oxidase (GOx)-encapsulated mesoporous hollow Co9S8 nanoreactors are constructed with the coverage of polyphenol diblock polymers containing poly(oligo(ethylene glycol) methacrylate) and dopamine moieties containing methacrylate polymeric block, which are termed as GOx@PCoS. After intravenous injection, tumor accumulation, and cellular uptake, GOx@PCoS deplete GSH by Co3+ ions. GOx inside the nanoreactors produce H2O2 via oxidation of glucose to enhance •OH-based chemodynamic therapy (CDT) through the Fenton-like reaction under the catalysis of Co2+. Moreover, Co3+ ions possess catalase activity to catalyze production of O2 from H2O2 to relieve tumor hypoxia. Upon 808 nm laser irradiation, GOx@PCoS exhibit photothermal and photodynamic effects with a high photothermal conversion efficiency (45.06%) and generation capacity of the toxic superoxide anion (•O2-) for photothermal therapy (PTT) and photodynamic therapy (PDT). The synergetic antitumor effects can be realized by GSH depletion, starvation, and combined CDT, PTT, and PDT with enhanced efficacy. Notably, GOx@PCoS can also be used as a magnetic resonance imaging (MRI) contrast agent to monitor the antitumor performance. Thus, GOx@PCoS show great potentials to effectively modulate TME and perform synergistic multimodal therapy.

Insight into the Prospects for Tumor Therapy Based on Photodynamic Immunotherapy.

Malignancy is one of the common diseases with high mortality worldwide and the most important obstacle to improving the overall life expectancy of the population in the 21st century. Currently, single or combined treatments, including surgery, chemotherapy, and radiotherapy, are still the mainstream regimens for tumor treatment, but they all present significant side effects on normal tissues and organs, such as organ hypofunction, energy metabolism disorders, and various concurrent diseases. Based on this, theranostic measures for the highly selective killing of tumor cells have always been a hot area in cancer-related fields, among which photodynamic therapy (PDT) is expected to be an ideal candidate for practical clinical application due to its precise targeting and excellent safety performance, so-called PDT refers to a therapeutic method mainly composed of photosensitizers (PSs), laser light, and reactive oxygen species (ROS). Photoimmunotherapy (PIT), a combination of PDT and immunotherapy, can induce systemic antitumor immune responses and inhibit continuing growth and distant metastasis of residual tumor cells, demonstrating a promising application prospect. This article reviews the types of immune responses that occur in the host after PDT treatment, including innate and adaptive immunity. To further help PIT-related drugs improve their pharmacokinetic properties and bioavailability, we highlight the potential improvement of photodynamic immunotherapy from three aspects: immunostimulatory agents, tumor-associated antigens (TAAs) as well as different immune cells. Finally, we focus on recent advances in various strategies and shed light on their corresponding mechanisms of immune activation and possible clinical applications such as cancer vaccines. Having discovered the inherent potential of PDT and the mechanisms that PDT triggers host immune responses, a variety of immunotherapeutic strategies have been investigated in parallel with approaches to improve PDT efficiency. However, it remains to be further elucidated under what conditions the immune effect induced by PDT can achieve tumor immunosuppression and to what extent PDT-induced antitumor immunity will lead to complete tumor rejection. Currently, PIT presents several outstanding intractable challenges, such as the aggregation ability of PSs locally in tumors, deep tissue penetration ability of laser light, immune escape, and biological toxicity, and it is hoped that these issues raised will help to point out the direction of preclinical research on PIT and accelerate its transition to clinical practice.

Aza-BODIPY based carbonic anhydrase IX: Strategy to overcome hypoxia limitation in photodynamic therapy.

Hypoxia caused by photodynamic therapy (PDT) is a major hurdle to cancer treatment since it can promote recurrence and progression by activating angiogenic factors, lowering therapeutic efficacy dramatically. In this work, AZB-I-CAIX2 was developed as a carbonic anhydrase IX (CAIX)-targeting NIR photosensitizer that can overcome the challenge by utilizing a combination of CAIX knockdown and PDT. AZB-I-CAIX2 showed a specific affinity to CAIX-expressed cancer cells and enhanced photocytotoxicity compared to AZB-I-control (the molecule without acetazolamide). Moreover, selective detection and effective cell cytotoxicity of AZB-I-CAIX2 by PDT in hypoxic CAIX-expressed murine cancer cells were achieved. Essentially, AZB-I-CAIX2 could minimize tumor size in the tumor-bearing mice compared to that in the control groups. The results suggested that AZB-I-CAIX2 can improve therapeutic efficiency by preventing PDT-induced hypoxia through CAIX inhibition.

Synthesis of Photosensitizers Based on Tetrapyrrolic Macrocycles for Combination with Antibiotics: Dual Inactivation of Bacteria.

The combination of photodynamic therapy with antibiotics or antimicrobial peptides for inactivation of bacteria is an area of growing interest due to the synergistic effect already observed by many authors. It has been shown that the efficiency of this dual antimicrobial therapy is highly dependent on the structure of the photosensitizer, being tetrapyrrolic macrocycles the ones with most promising results. There are a few review articles in the recent literature describing the main microbiological results concerning this dual inactivation of bacteria, but none of them focus on the synthetic processes of these photosensitizers and their remarkable chemical versatility. Therefore, herein we present an overview on synthetic methodologies for preparation of tetrapyrrolic macrocycles and their conjugates with antibiotics or antimicrobial peptides, for use in dual inactivation of bacteria. This review will be divided in two sections concerning the physical or covalent combinations of PS with antibiotic/cationic peptides, followed by brief critical analysis on their corresponding antimicrobial outcomes.

Phthalocyanine-Based Nanoassembly with Switchable Fluorescence and Photoactivities for Tumor Imaging and Phototherapy.

Switchable theranostics are of great interest for accurate tumor imaging and targeted therapy. Here, we develop smart engineering to construct nanostructured phthalocyanines self-assembled by amphiphilic zinc phthalocyanines (ZnPcs) and hydrophobic copper phthalocyanines (CuPcs) (ZnPc(PEG)5:CuPc-N, where ZnPc(PEG)5 is monosubstituted ZnPcs with pentaethylene glycol as the substituent). The fluorescence and reactive oxygen species generation of ZnPc(PEG)5:CuPc-N can be triggered depending on the membrane of the tumor cells for the imaging and photoactivities. Concerning the stability in blood circulation, the surface of the nanocomplex is coated with polydopamine, which responds to the tumor acidic microenvironment. ZnPc(PEG)5 and CuPc focus on photodynamic and photothermal properties, respectively, and can be stimulated by a single laser beam, endowing ZnPc(PEG)5:CuPc-N a combined antitumor effect from evaluations both in vitro and in vivo. In our study, the mechanism of switchable theranostics, the strategy of combined photodynamic and photothermal therapy, and the smart nanoengineering technology of phthalocyanines with poor water solubility can be applied to other phthalocyanines or phthalocyanine-like phototherapy agents.

Recent progress in cancer therapy based on the combination of ferroptosis with photodynamic therapy

Current anticancer treatments have many limitations to achieving high efficacy. Hence, novel strategies that broaden therapeutic prospects must urgently be developed. Ferroptosis is an iron-dependent form of non-apoptotic programmed cell death that is induced by cellular antioxidative system inhibition. Photodynamic therapy (PDT) uses photosensitizers to generate reactive oxygen species and aggravate oxidative stress in tumor cells. Combining ferroptosis with PDT cooperatively regulates intracellular redox homeostasis, thus increasing cancer cell susceptibility to oxidative stress and yielding synergistic anticancer effects. In this review, various strategies for combining ferroptosis with PDT are comprehensively summarized and discussed, including mono-PDT and PDT-induced ferroptosis, combining PDT with small-molecule ferroptosis inducers, and combining PDT with metal-ion-induced ferroptosis. Additionally, the possibility of combining ferroptosis and PDT with other anti-tumor therapies is discussed. Finally, the prospects and challenges of combining ferroptosis with PDT in clinical cancer treatment are addressed. With increased understanding of the superiority of combination PDT with ferroptosis for cancer treatment, we hope that drug delivery systems based on this strategy will be further developed to increase anticancer efficiency and achieve successful clinical translation.

Fractional CO2 laser - assisted methylene blue photodynamic therapy is a potential alternative therapy for onychomycosis in the era of antifungal resistance

BackgroundTreatment of onychomycosis is challenging by virtue of the impact of nail disfigurement, the location of the fungi within the nail and reported antifungal resistance worldwide. Light-based technologies are promising primary or adjunctive therapeutic modalities. We aimed to compare the efficacy of photodynamic therapy and fractional CO2 laser monotherapy either alone or in combination for onychomycosis. Patients and methodsThis prospective randomized comparative study was conducted on 51 onychomycosis patients divided into three groups. In group A, patients were treated using 6 photodynamic therapy sessions using methylene blue and IPL (560 to 700 nm, fluence 12 J/cm2). Group B patients were treated using 6 bimonthly fractional CO2 laser sessions (10,600 nm, 1.600 mj energy and 0.6 mm density) and group C patients were treated using 6 combined fractional CO2 laser and photodynamic therapy sessions. Patients were evaluated mycologically, dermoscopically and clinically by calculation of proximal nail diameter percentage at baseline, monthly, at the end of treatment and after a 6‐month follow‐up period post-treatment. ResultsCandida was the most commonly isolated organismin in 64.7%, 70.6% and 70.6% of the pateints in groups A, B and C, respectively. The dermoscopic findings in the total dystrophic onychomycosis was subungual hyperkeratosis in 6 patients (100%), longitudinal streaks and striae in 1 patient (16.7%). In dorsolateral subungual onychomycosis, jagged proximal edge in 31 patients (70.5%), and pigmentation in 30 patients (68.2%) were noted. In proximal subungual onychomycosis irregular matt patches were seen in 1 patient (100%). Proximal nail diameter percentage showed statistically significant improvement after treatment and 6 months follow up in the 3 studied groups. Mean increase of proximal nail diameter after treatment was highest in group C (52.94 ± 20.24), followed by group B (43.82 ± 21.03) and least in group A (35.29 ± 17.0). This difference was statistically significant (p = 0.044). Reported side effects were mild-moderate pain, discoloration and paronychia. ConclusionWe conclude that fractional CO2 laser and photodynamic monotherapy, and their combination achieve high success rates, good patient satisfaction and safety profile. Fractional CO2-assisted photodynamic therapy is associated with the highest improvement over either fractional CO2 or photodynamic therapy alone.

Superficial shaving combined with photodynamic therapy is effective as a treatment for condyloma acuminatum

AbstractCondyloma acuminatum is a common sexually transmitted disease caused by human papillomavirus. Its prevalence and recurrence rates are high. While there are multiple treatment options for condyloma acuminatum, no single therapy form is effective in achieving complete remission. Photodynamic therapy (PDT) was shown to be very promising as a treatment option for condyloma acuminatum. However, for some patients the therapeutic result after a single PDT session is not satisfactory. Thus, it is necessary to develop an effective treatment method for recalcitrant condyloma acuminatum.We hypothesize that suboptimal therapeutic results after a single PDT may be caused by an insufficient penetration of the photosensitizer into the tissue. Here, we applied a combination of superficial shaving and PDT to address this issue. All patients were satisfied with the effect of the treatment, and their quality of life improved significantly. Pain was the major adverse event during treatment but was acceptable to all patients. Therefore, superficial shaving in combination with PDT is safe and effective.

Comprehensive treatment of patients with autoimmune thyroiditis using laser technologies

Background. The frequency of autoimmune thyroiditis reaches up to 40% among all thyroid gland diseases and ranks second among endocrinological diseases.
 Aim. Carrying out a comparative evaluation of the effectiveness of laser photodynamic therapy and traditional conservative treatment in diffuse form of autoimmune thyroiditis.
 Material and methods. The work is based on the examination and treatment data of 235 patients hospitalized in the Scientific Center of Surgery named after M.A. Topchubashov for the period from 2008 to 2021. Patients were divided into two groups based on the applied methods of treatment. Patients of the main group (106 people, 45.1%) received sessions of laser photodynamic therapy in combination with intravenous laser blood irradiation with low-intensity laser radiation. Patients in the control group (129 people, 54.9%) received a course of conservative therapy in combination with sessions of intravenous laser blood irradiation with low-intensity laser radiation. To test the statistical significance of differences in the concentrations of thyroid hormones, pituitary gland and antibodies to thyroid tissues in the blood serum of patients before and on the 15th day after treatment, Pearson's 2 test was used. In each group, the mean values of the analyzed clinical parameters, their mean error (m), 95% confidence interval, and the significance of intergroup differences were calculated according to Pearson's 2, MannWhitney U, and Student's t criteria. Differences were considered statistically significant at p 0.050.
 Results. In the main group on the 5th day of treatment, normalization of the main indicators of the inflammatory response occurred in 26 (24.5%) patients, in the control group in 16 (12.4%) patients (2=5.9, p=0.010). In patients of the main group, the levels of antibodies to thyroperoxidase on the 15th day after treatment, compared with their values before treatment, decreased by 5.65 times (t=8.4, p 0.001), the content of thyroid-stimulating hormone decreased by 2.18 times (t=6.9, p 0.001), free thyroxine increased 2 times (t=3.4, p 0.01), free triiodothyronine increased 1.71 times (t=1.4, p 0.05). The average values of antibodies to thyroperoxidase in the main group after treatment were within the normal range (31.575.75 IU/ml).
 Conclusion. The use of laser photodynamic therapy provides the best results in the treatment of patients with diffuse autoimmune thyroiditis.

Radiofrequency thermal balloon angioplasty of vulnerable atherosclerotic plaque accompanied by delta-aminolevulinic acid photodynamic therapy and catheter-based samarium-153 brachytherapy

Abstract Background The balloon angioplasty methods that are currently in use, cause to inflammation and subsequent neoatherosclerosis. Purpose The aim of this study was to evaluate the effect of combined photodynamic therapy and brachytherapy on inflammation and intimal hyperplasia reduction after radiofrequency thermal balloon angioplasty of carotid artery in an animal model of thin fibrous cap atheromatous plaque, wherein a high resolution diagnostic ultrasound is adjuncted with angioplasty and combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits were submitted to carotid artery vulnerable atherosclerotic plaque by primary intravascular balloon injury followed by a 1.5% cholesterol-rich diet for eight weeks. Histopathology results showed the formation of advanced atherosclerosis with a foam cell-rich atheromatous plaque, resulted in severe stenosis (>70%) in all of the rabbits' arteries. Then treatment group underwent B-mode ultrasound-guided radiofrequency thermal balloon angioplasty followed by catheter-based samarium-153 brachytherapy (153Sm, 18 Gy, β particles) and photosensitizer delta-aminolevulinic acid (delta-ALA)-mediated fiber optic catheter-based polarized light-emitting diodes (LEDs) violet light (λ±Δλ = 405±5 nm, E/A = 120 J/cm2) photodynamic therapy. Results Results from ultrasonography and histopathology showed a significant reduction in the mean value for macrophages, lymphocytes, mast cells, foam cells and hyperplastic vascular smooth muscle cells density after angioplasty in the treatment group compared with the other groups (p<0.05). Conclusion Apoptotic effect of brachytherapy in combination with cytotoxic and anti-inflammatory effect of delta-ALA photodynamic therapy on immune cells and hyperplastic vascular smooth muscle cells, can cause to reduce the neoatherosclerosis in the intimal layer. These findings provide the basis for developing of combined brachytherapy and photodynamic therapy for a successful clinical application in the inhibition of neoatherosclerosis after radiofrequency thermal balloon angioplasty. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab

Combination of 5-Fluorouracil with Photodynamic Therapy: Enhancement of Innate and Adaptive Immune Responses in a Murine Model of Actinic Keratosis†.

We previously showed that a combination of differentiation-inducing agents (5-fluorouracil [5FU], vitamin D3 or methotrexate) and aminolevulinate-based photodynamic therapy (PDT) improves clinical responses by enhancing protoporphyrin IX (PpIX) photosensitizer levels and cell death. Here, we show that in addition to its previously known effects, 5FU enhances PDT-induced tumor-regressing immunity. Murine actinic keratoses were treated with topical 5FU or vehicle for 3 days prior to aminolevulinic acid application, followed by blue light illumination (~417 nm). Lesions were harvested for time-course analyses of innate immune cell recruitment into lesions, i.e. neutrophils (Ly6G+) and macrophages (F4/80+), which peaked at 72 h and 1 week post-PDT, respectively, and were greater in 5FU-treated lesions. Enhanced infiltration of activated T cells (CD3+) throughout the time course, and of cytotoxic T cells (CD8+) at 1-2 weeks post-PDT, also occurred in 5FU-treated lesions. 5FU pretreatment reduced the presence of cells expressing the immune checkpoint marker PD-1 at ~72 h post-PDT, favoring cytotoxic T cell activity. A combination of 5FU and PDT, each individually known to induce long-term tumor-targeting immune responses in addition to their more immediate effects on cancer cells, may synergize to provide better management of squamous precancers.

Overview of Nanoparticle-Based Approaches for the Combination of Photodynamic Therapy (PDT) and Chemotherapy at the Preclinical Stage.

The widespread diffusion of photodynamic therapy (PDT) as a clinical treatment for solid tumors is mainly limited by the patient's adverse reaction (skin photosensivity), insufficient light penetration in deeply seated neoplastic lesions, unfavorable photosensitizers (PSs) biodistribution, and photokilling efficiency due to PS aggregation in biological environments. Despite this, recent preclinical studies reported on successful combinatorial regimes of PSs with chemotherapeutics obtained through the drugs encapsulation in multifunctional nanometric delivery systems. The aim of the present review deals with the punctual description of several nanosystems designed not only with the objective of co-transporting a PS and a chemodrug for combination therapy, but also with the goal of improving the therapeutic efficacy by facing the main critical issues of both therapies (side effects, scarce tumor oxygenation and light penetration, premature drug clearance, unspecific biodistribution, etc.). Therefore, particular attention is paid to the description of bio-responsive drugs and nanoparticles (NPs), targeted nanosystems, biomimetic approaches, and upconverting NPs, including analyzing the therapeutic efficacy of the proposed photo-chemotherapeutic regimens in in vitro and in vivo cancer models.

34071 Combination of photodynamic therapy and oral antifungals for the treatment of onichomycosis

Background: Onychomycosis (OM) represents 50% of nail pathology, making it one of the most prevalent fungal diseases and a therapeutic challenge. Photodynamic therapy (PDT) could be a therapeutic alternative due to its good adherence, low probability of resistance, no interaction with drugs, and acceptable risk-benefit. Patients and methods: Retrospective observational study that included all patients with a microbiological diagnosis of OM treated with PDT in our service (2013-2021). The protocol used was 16% methyl-aminolevulinate (MAL) as a photosensitizer and red light (37 J/cm2), every 1 or 2 weeks. Antifungal intake was recorded and whether a previous treatment with 40% urea was performed. Results: Twenty patients were included, 55% men, with a mean age of 59 ± 17 years. The most frequent microorganism was T rubrum (55%) and the most frequent location was the feet (90%), half associated with tinea pedis. The mean number of sessions was 6.3. Fifty percent required treatment with terbinafine 250 mg/day, although the majority (8) only for 1 month, and 3 patients with topical terbinafine achieving a resolution of 60%. Discussion: Studies support the efficacy of PDT alone or in combination with urea or different photosensitizers (methylene-blue, ALA and MAL), associated or not with keratolytics. However, there is only 1 study of PDT as adjuvant therapy demonstrating its ability to accelerate its resolution. We conclude that PDT is an alternative to the treatment of OM either in monotherapy or adjuvant, reducing the dose of antifungal agents, thus avoiding the comorbidity that it entails and achieving even higher cure rates.

Combining Radiotherapy (RT) and Photodynamic Therapy (PDT): Clinical Studies on Conventional RT-PDT Approaches and Novel Nanoparticle-Based RT-PDT Approaches under Preclinical Evaluation.

Radiotherapy (RT) is the primary standard of care for many locally advanced cancers. Often times, however, the efficacy of RT is limited due to radio-resistance that cancer cells develop. Photodynamic therapy (PDT) has gained importance as an alternative local therapy. Because its mechanism involves minimal acquired resistance, PDT is a useful adjunct to RT. This review discusses recent advances in combining RT with PDT for cancer treatment. In the first part of this review, we will discuss clinical trials on RT + PDT combination therapies. All these approaches suffer from the same inherent limitations as any current PDT methods; (i) visible light has a short penetration depth in human tissue (<∼10 mm), and (ii) it is difficult to illuminate the entire tumor homogeneously by external/interstitial laser irradiation. To address these limitations, scintillating nanoparticle-mediated RT-PDT approaches have been explored in which nanoparticles convert X-rays (RT) into visible light (PDT); high-energy X-rays can reach deep into the body to irradiate cancers uniformly and precisely. The second part of this review will discuss recent efforts in developing and applying nanoparticles for RT-PDT applications.