Administration Of Photosensitizer Research Articles

Carrier-Free, Amorphous Verteporfin Nanodrug for Enhanced Photodynamic Cancer Therapy and Brain Drug Delivery.

Glioblastoma (GBM) is hard to treat due to cellular invasion into functioning brain tissues, limited drug delivery, and evolved treatment resistance. Recurrence is nearly universal even after surgery, chemotherapy, and radiation. Photodynamic therapy (PDT) involves photosensitizer administration followed by light activation to generate reactive oxygen species at tumor sites, thereby killing cells or inducing biological changes. PDT can ablate unresectable GBM and sensitize tumors to chemotherapy. Verteporfin (VP) is a promising photosensitizer that relies on liposomal carriers for clinical use. While lipids increase VP's solubility, they also reduce intracellular photosensitizer accumulation. Here, a pure-drug nanoformulation of VP, termed "NanoVP", eliminating the need for lipids, excipients, or stabilizers is reported. NanoVP has a tunable size (65-150nm) and 1500-fold higher photosensitizer loading capacity than liposomal VP. NanoVP shows a 2-fold increase in photosensitizer uptake and superior PDT efficacy in GBM cells compared to liposomal VP. In mouse models, NanoVP-PDT improved tumor control and extended animal survival, outperforming liposomal VP and 5-aminolevulinic acid (5-ALA). Moreover, low-dose NanoVP-PDT can safely open the blood-brain barrier, increasing drug accumulation in rat brains by 5.5-fold compared to 5-ALA. NanoVP is a new photosensitizer formulation that has the potential to facilitate PDT for the treatment of GBM.

Enzyme‐Activatable Near‐Infrared Photosensitizer with High Enrichment in Tumor Cells Based on a Multi‐Effect Design

AbstractEnzyme‐activatable near‐infrared (NIR) fluorescent probes and photosensitizers (PSs) have emerged as promising tools for molecular imaging and photodynamic therapy (PDT). However, in living organisms selective retention or even enrichment of these reagents after enzymatic activation at or near sites of interest remains a challenging task. Herein, we integrate non‐covalent and covalent retention approaches to introduce a novel “1‐to‐3” multi‐effect strategy—one enzymatic stimulus leads to three types of effects—for the design of an enzyme‐activatable NIR probe or PS. Using this strategy, we have constructed an alkaline phosphatase (ALP)‐activatable NIR fluorogenic probe and a NIR PS, which proved to be selectively activated by ALP to switch on NIR fluorescence or photosensitizing ability, respectively. Additionally, these reagents showed significant enrichment (over 2000‐fold) in ALP‐overexpressed tumor cells compared to the culture medium, accompanied by massive depletion of intracellular thiols, the major antioxidants in cells. The investigation of this ALP‐activatable NIR PS in an in vivo PDT model resulted in complete suppression of HeLa tumors and full recovery of all tested mice. Encouragingly, even a single administration of this NIR PS was sufficient to completely suppress tumors in mice, demonstrating the high potential of this strategy in biomedical applications.

Switchable adhesive films of pullulan loaded with a deep eutectic solvent-curcumin formulation for the photodynamic treatment of drug-resistant skin infections.

Antimicrobial photodynamic therapy (aPDT) is a potent tool to surpass the global rise of antimicrobial resistance; still, the effective topical administration of photosensitizers remains a challenge. Biopolymer-based adhesive films can safely extend the residence time of photosensitizers. However, their wide application is narrowed by their limited water absorption capacity and gel strength. In this study, pullulan-based films with a switchable character (from a solid film to an adhesive hydrogel) were developed. This was accomplished by the incorporation of a betaine-based deep eutectic solvent (DES) containing curcumin (4.4μg.cm-2) into the pullulan films, which tuned the films' skin moisture absorption ability, and therefore they switch into an adhesive hydrogel capable of delivering the photosensitizer. The obtained transparent films presented higher extensibility (elongation at break up to 338.2%) than the pullulan counterparts (6.08%), when stored at 54% of relative humidity, and the corresponding hydrogels a 4-fold higher adhesiveness than commercial hydrogels. These non-cytotoxic adhesives allowed the inactivation (∼5 log reduction), down to the detection limit of the method, of multiresistant strains of Staphylococcus aureus in ex vivo skin samples. Overall, these materials are promising for aPDT in the treatment of resistant skin infections, while being easily removed from the skin.

New technologies for nephron-sparing surgery in upper urinary tract cancers.

Nephron-sparing surgery (NSS) is the preferred treatment in patients with low-risk upper tract urothelial carcinoma (UTUC). Improving both instruments and topical chemotherapy regimens efficacy is crucial to achieve better outcomes. The purpose of this review is to summarize the most recent evidence on technological advances for the conservative management of UTUC with implications on diagnosis and treatment. Novel diagnostic tools, lasers, and topical chemotherapy systems delivery have been implemented to optimize NSS outcomes for UTUC. Photodynamic ureteroscopy has been reported to improve cancer detection rate as compared with conventional imaging or ureteroscopy, especially in case of carcinoma in situ. However, refinements in photosensitizer administration and dedicated instruments are needed. The armamentarium of lasers for UTUC ablation is composed of several devices with peculiar characteristics. Together with Ho:YAG and Tm:YAG lasers, the Thulium Fiber Laser (TFL) is gaining momentum in UTUC ablation. Strengths and weaknesses of each laser must be considered to maximize oncological and safety outcomes. Several novel endocavitary chemotherapy delivery systems have been tested to reduce tumor recurrence and progression after NSS. Administration of gel-based chemotherapeutic agents has been proven to be effective in humans; conversely, drug-eluting ureteral stent systems are still conceptual.

Systematic Review of Photodynamic Therapy in Gliomas.

Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Being highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard of care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.

Ultrasound-triggered piezocatalytic composite hydrogels for promoting bacterial-infected wound healing.

Wound healing has become one of the basic issues faced by the medical community because of the susceptibility of skin wounds to bacterial infection. As such, it is highly desired to design a nanocomposite hydrogel with excellent antibacterial activity to achieve high wound closure effectiveness. Here, based on ultrasound-triggered piezocatalytic therapy, a multifunctional hydrogel is designed to promote bacteria-infected wound healing. Under ultrasonic vibration, the surface of barium titanate (BaTiO3, BT) nanoparticles embedded in the hydrogel rapidly generate reactive oxygen species (ROS) owing to the established strong built-in electric field, endowing the hydrogel with superior antibacterial efficacy. This modality shows intriguing advantages over conventional photodynamic therapy, such as prominent soft tissue penetration ability and the avoidance of serious skin phototoxicity after systemic administration of photosensitizers. Moreover, the hydrogel based on N-[tris(hydroxymethyl)methyl]acrylamide (THM), N-(3-aminopropyl)methacrylamide hydrochloride (APMH) and oxidized hyaluronic acid (OHA) exhibits outstanding self-healing and bioadhesive properties able to accelerate full-thickness skin wound healing. Notably, compared with the widely reported mussel-inspired adhesive hydrogels, OHA/THM-APMH hydrogel due to the multiple hydrogen bonds from unique tri-hydroxyl structure overcomes the shortage that catechol groups are easily oxidized, giving it long-term and repeatable adhesion performance. Importantly, this hybrid hydrogel confines BT nanoparticles to wound area and locally induced piezoelectric catalysis under ultrasound to eradicate bacteria, markedly improving the therapeutic biosafety and exhibits great potential for harmless treatment of bacteria-infected tissues.

Buccal mucosal application of dissolvable microneedle patch containing photosensitizer provides effective localized delivery and phototherapy against oral carcinoma

The effectiveness of phototherapy using photosensitizers is limited by the challenges in their delivery at the site of irradiation. Here, we demonstrate the localized application of a photosensitizer-loaded microneedle patch for effective photodynamic and photothermal therapy in oral carcinoma. Indocyanine green (ICG) was studied as a photosensitizer for its effect on oral carcinoma, FaDu cells. Different parameters including concentration, near-infrared (NIR) laser irradiation intensity and irradiation time were optimized while measuring temperature increase and reactive oxygen species (ROS) generation in FaDu cells. A dissolvable microneedle (DMN) patch made of sodium carboxymethyl cellulose and sodium alginate was fabricated by the micromolding technique. DMN showed sufficient mechanical strength for insertion in the excised porcine buccal mucosa. DMN dissolved within 30 s in phosphate buffer and 30 min in the excised buccal mucosa. Confocal microscopy studies revealed DMN penetration up to a depth of 300 µm within the buccal mucosa. ICG-DMN applied on the back of the rat was found to be localized at the application site before and after irradiation using an 808 nm NIR laser. ICG-DMN was applied on the FaDu xenografted tumor model in athymic nude mice. The localized temperature increase and ROS generation significantly (P < 0.05) decreased the tumor volume after ICG-DMN application compared with the control group. In conclusion, DMN can be developed for the localized administration of photosensitizers for phototherapy in oral carcinoma.

Combination of Two Photosensitisers in Anticancer, Antimicrobial and Upconversion Photodynamic Therapy.

Photodynamic therapy (PDT) is a special form of phototherapy in which oxygen is needed, in addition to light and a drug called a photosensitiser (PS), to create cytotoxic species that can destroy cancer cells and various pathogens. PDT is often used in combination with other antitumor and antimicrobial therapies to sensitise cells to other agents, minimise the risk of resistance and improve overall outcomes. Furthermore, the aim of combining two photosensitising agents in PDT is to overcome the shortcomings of the monotherapeutic approach and the limitations of individual agents, as well as to achieve synergistic or additive effects, which allows the administration of PSs in lower concentrations, consequently reducing dark toxicity and preventing skin photosensitivity. The most common strategies in anticancer PDT use two PSs to combine the targeting of different organelles and cell-death mechanisms and, in addition to cancer cells, simultaneously target tumour vasculature and induce immune responses. The use of PDT with upconversion nanoparticles is a promising approach to the treatment of deep tissues and the goal of using two PSs is to improve drug loading and singlet oxygen production. In antimicrobial PDT, two PSs are often combined to generate various reactive oxygen species through both Type I and Type II processes.

Efficacy of Photodynamic Therapy with Chlorine-Based Photosensitizer in the Treatment of Basal Cell Carcinomas

The aim of this study is to evaluate a safety and antitumor efficacy of photodynamic therapy (PDT) with chlorine-based photosensitizer (PS) for treatment patients with basal cell skin carcinomas (BCC).&#x0D; Material and Methods: The work was performed on the basis of the Department of hyperthermia and photodynamic therapy. The object of the study were 172 patients with a verified diagnosis of BCC (T1N0M0, I stage), who received treatment from 2007 to 2022. PS «Photolon» (RUE «Belmedpreparaty», Republic of Belarus) was administrated intravenously at a dose of 2.0-2.5 mg/kg. The session of PDT was performed 2.5-3 h after intravenous injection of PS using semiconductor lasers (λ=660±5 nm) with exposure doses 50-250 J/cm² and power density – 0.15-0.5 W/cm². Frequency and severity of side effects after treatment session was assessed based on the criteria CTCAE (Version 4.03; 2010). The antitumor efficacy was evaluated 3 months after treatment. Clinical outcome was evaluated visually and morphologically by cytological or histopathological examination. Performance criteria were as follows (according to WHO, 1979).&#x0D; Results: The phenomenon of skin phototoxicity due to violation of the light regime (hyperemia, burning, slight swelling of the soft tissues of the face; CTCAE, I-II grades) was registered in 5.8% of cases (n=10). Serious adverse reactions (anaphylactic shock, Quincke's edema, severe pain syndrome) after the administration of PS and photoirradiation were not identified. Complete and partial regressions of tumors was observed in 93.0% and 4.7% of patients, respectively. The objective answer was 97.7%. The frequency of local relapses of the disease 1, 2, 3, 4 and 5 years after PDT was 3.1%, 3.1%, 4.6%, 4.6% and 6.9%, respectively.&#x0D; Сonclusion: PDT is a well-tolerated and highly effective therapeutic option in patients with BCC.

Preliminary Toxicity Evaluation of a Porphyrin Photosensitizer in an Alternative Preclinical Model.

In photodynamic therapy (PDT), a photosensitizer (PS) excited with a specific wavelength, and in the presence of oxygen, gives rise to photochemical reactions that lead to cell damage. Over the past few years, larval stages of the G. mellonella moth have proven to be an excellent alternative animal model for in vivo toxicity testing of novel compounds and virulence testing. In this article, we report a series of preliminary studies on G. mellonella larvae to evaluate the photoinduced stress response by a porphyrin (PS) (TPPOH). The tests performed evaluated PS toxicity on larvae and cytotoxicity on hemocytes, both in dark conditions and following PDT. Cellular uptake was also evaluated by fluorescence and flow cytometry. The results obtained demonstrate how the administration of PS and subsequent irradiation of larvae affects not only larvae survival rate, but also immune system cells. It was also possible to verify PS's uptake and uptake kinetics in hemocytes, observing a maximum peak at 8 h. Given the results obtained in these preliminary tests, G. mellonella appears to be a promising model for preclinical PS tests.

Ras-transfected human mammary tumour cells are resistant to photodynamic therapy by mechanisms related to cell adhesion

AimsPhotodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage.Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT. Materials and methodsWe employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs. Key findingsWe found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation.Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions.HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells. SignificanceKnowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.

Modifying aluminum phthalocyanine with quantum dots to promote cellular uptake and enhance the efficacy of anticancer photodynamic therapy

Photodynamic therapy (PDT) is regarded as an alternative anti-tumor therapy which involves the administration of photosensitizers (PSs) and irradiation with specific light. However, conventional PDT therapy has been limited to the efficiency of PS delivery. A nanocarrier system could provide an effective platform for PS delivery and improve the efficiency of antitumor PDT. In this article, we prepared a complex consisting of aluminum phthalocyanine (AlPcS) and CdSe/CdZnS core-shell structure QDs and investigated the interaction between the complex and tumor cells. A more significant internalization of the conjugation was observed compared to free AlPcS via confocal fluorescence imaging. The tumor cells exhibited an obvious apoptotic trend after QD–AlPcS-mediated PDT.

Experience of using photodynamic therapy in early stages of penile cancer

Background. Penile cancer is a rare oncological pathology. Due to the intimate nature of the affected area and high significance of the organ for psycho-emotional state of the patient, at the early stages of the disease organ-sparing operations are preferred allowing to minimize the effect on patient’s quality of life without affecting oncological results.Aim. To evaluate the effectiveness of treatment of early stages penile cancer using photodynamic therapy (PDT) with chlorin E6 derivatives.Materials and methods. Between 2017 and 2021, PDT with chlorin E6 derivatives to treat early-stage penile cancer was performed in 15 patients between the ages of 29 and 84 years (mean age 56.4 years). Tumor stage was Tin situ–1bN0M0. PDT was performed with preliminary administration of Photolon and Photoran photosensitizers. Laser exposure on the tumor lesions was performed 3 hours after photosensitizer administration using laser device Latus-2 (662 nm), light dose 200–300 J/cm2, power density 0.21–0.41 mW/cm2.Results. After 1 PDT session, full regression was observed in 11 (73.3 %) patients, partial regression in 4 (26.7 %) patients who underwent 2nd session 2 months later with full effect. Therefore, in all patients full regression of the tumors was achieved. Follow-up duration was 6–56 months. Recurrence was diagnosed in 1 (6.7 %) patient 36 months after PDT, 14 (93.3 %) patients are under observation without signs of local recurrence, among them for more than 4 years – 3 men, more than 3 years – 1, more than 2 years – 3, more than 1 year – 4 and more than 6 months – 3. During the follow-up, no regional or distant metastases were observed in any of the patients.Conclusion. PDT with chlorin E6 derivatives is an effective organ-sparing treatment method for early-stage penile cancer with satisfactory oncological results without negative effect on patients’ quality of life. In 93.3 % of patients, local recurrence of the disease was not observed; during follow-up no distant metastases were diagnosed. It is necessary to point out satisfactory cosmetic results of the treatment: in all patients, elastic non-deforming scars were formed with full preservation of anatomical structures of the penis, no erectile dysfunction or disruption of urination were observed after PDT.

Photodynamic Therapy for Bladder Cancers, A Focused Review†.

Bladder cancer is the first cancer for which PDT was clinically approved in 1993. Unfortunately, it was unsuccessful due to side effects like bladder contraction. Here, we summarized the recent progress of PDT for bladder cancers, focusing on photosensitizers and formulations. General strategies to minimize side effects are intravesical administration of photosensitizers, use of targeting strategies for photosensitizers and better control of light. Non-muscle invasive bladder cancers are more suitable for PDT than muscle invasive and metastatic bladder cancers. In 2010, the FDA approved blue light cystoscopy, using PpIX fluorescence, for photodynamic diagnosis of non-muscle invasive bladder cancer. PpIX produced from HAL was also used in PDT but was not successful due to low therapeutic efficacy. To enhance the efficacy of PpIX-PDT, we have been working on combining it with singlet oxygen-activatable prodrugs. The use of these prodrugs increases the therapeutic efficacy of the PpIX-PDT. It also improves tumor selectivity of the prodrugs due to the preferential formation of PpIX in cancer cells resulting in decreased off-target toxicity. Future challenges include improving prodrugs and light delivery across the bladder barrier to deeper tumor tissue and generating an effective therapeutic response in an In vivo setting without causing collateral damage to bladder function.

Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Radiodynamic Therapy with Chlorine-Based Photosensitizer on Pliss Lymphosarcoma Solid Tumor: In Vivo Experiment

The aim of this study was to investigate the antitumor efficacy of radiodynamic therapy (RDT) with a chlorin-based photosensitizer (PS) in an in vivo experiment.&#x0D; Material and Methods: The study was performed in 35 white outbred rats weighing 180±30 g. Subcutaneously transplanted Pliss lymphosarcoma (PLS) was used as tumor model. Chlorin-based PS «Photolon» (RUE «Belmedpreparaty», Republic Belarus) was injected intravenously at a dose of 2.5 mg/kg. The radiation therapy sessions (RT) were carried out once 2.5–3 hours after the administration of the PS by the contact method on the device «microSelectron-HDR V3 Digital» (Elekta, Sweden) using γ-radiation (192Ir) in single focal doses (SFD) 2, 4 and 6 Gy. All laboratory animals were subdivided into 7 groups of 5 animals each: intact control, RT 2 Gy, RT 4 Gy, RT 6 Gy, PS + RT 2 Gy, PS + RT 4 Gy and PS + RT 6 Gy. The antitumor effectiveness of exposure was evaluated according to the indicators characterizing the dynamics of volume changes: Vav. (cm3), the coefficient of absolute tumor growth (K, units) and the coefficient of tumor growth inhibition (TGI, %). The frequency of complete regressions (СR) was estimated 60 days after the performed exposures. In each group, the share of animals (%) with no visual and palpatory signs of tumor growth was evaluated. The differences were considered statistically significant at the significance level of p&lt;0.05.&#x0D; Results: On the 16th day from the beginning of the experiment Vav. in groups were 39.07±4.19; 23.06±3.25 (р=0.012); 35.04±2.35 (р=0.419); 25.83±3.06 (р=0.027); 28.36±3.45 (0.074); 25.47±1.88 (р=0.013) and 16.56±3.64 cm3 (р=0,002), respectively. The K coefficients in the experimental groups were 1219.94; 657.86; 1296.78; 716.50; 833.12; 669.26 and 590.43 units, respectively. The TGI coefficients in the experimental groups were 40.98%; 10.31%; 33.89%; 27.41%; 34.81% and 57.61%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 20%, 0%, 0%, 0%, 0% and 40%, respectively.&#x0D; Conclusion: RDT is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of X-rays. Systemic administration of chlorin-based PS before the RT session increases the antitumor efficacy of RT in animals with PLS transplantable tumors. The data obtained indicate that further studies of the radiosensitizing properties of PS are promising.

Recent advances in engineered polymeric materials for efficient photodynamic inactivation of bacterial pathogens.

Nowadays, infectious diseases persist as a global crisis by causing significant destruction to public health and the economic stability of countries worldwide. Especially bacterial infections remain a most severe concern due to the prevalence and emergence of multi-drug resistance (MDR) and limitations with existing therapeutic options. Antibacterial photodynamic therapy (APDT) is a potential therapeutic modality that involves the systematic administration of photosensitizers (PSs), light, and molecular oxygen (O2) for coping with bacterial infections. Although the existing porphyrin and non-porphyrin PSs were effective in APDT, the poor solubility, limited efficacy against Gram-negative bacteria, and non-specific distribution hinder their clinical applications. Accordingly, to promote the efficiency of conventional PSs, various polymer-driven modification and functionalization strategies have been adopted to engineer multifunctional hybrid phototherapeutics. This review assesses recent advancements and state-of-the-art research in polymer-PSs hybrid materials developed for APDT applications. Further, the key research findings of the following aspects are considered in-depth with constructive discussions: i) PSs-integrated/functionalized polymeric composites through various molecular interactions; ii) PSs-deposited coatings on different substrates and devices to eliminate healthcare-associated infections; and iii) PSs-embedded films, scaffolds, and hydrogels for regenerative medicine applications.

Microneedle Patches with O2 Propellant for Deeply and Fast Delivering Photosensitizers: Towards Improved Photodynamic Therapy.

Photodynamic therapy (PDT) is an emerging technique for treating tumors. Especially, topical administration of photosensitizers (PSs) is more favorable for superficial tumor treatments with low systematic phototoxicity. Yet, ineffective migration of PSs to targeted tumor tissues and rapid consumption of O2 during PDT greatly limit their effects. Herein, PS‐loaded microneedle (MN) patches with O2 propellant for a deeper and faster transdermal delivery of PS and improved PDT by embedding sodium percarbonate (SPC) into dissolving poly(vinyl pyrrolidone) MNs are presented. It is shown that SPC in the MNs can react with surrounding fluid to generate gaseous oxygen bubbles, forming vigorous fluid flows and thus greatly enhancing PS of chlorin e6 (Ce6) penetration in both hydrogel models and skin tissues. Reactive oxygen species (ROS) in hypoxic breast cancer cells (4T1 cells) are greatly increased by rapid penetration of PS and relief of hypoxia in vitro, and Ce6‐loaded SPC MNs show an excellent cell‐killing effect. Moreover, lower tumor growth rate and tumor mass after a 20‐d treatment in tumor‐bearing mice model verify the improved PDT in gaseous oxygen‐droved delivery of PS. This study demonstrates a facile yet effective route of MN delivery of PSs for improved PDT in hypoxic tumor treatment.

On the Pathomorphological Pattern of the Efficiency of Photodynamic Therapy of Murine Melanoma B16 Using a New Photosensitizer Based on Chlorin e6 Conjugate with a Prostate-Specific Membrane Antigen.

Photodynamic therapy (PDT) is an effective treatment for a number of solid malignancies. In this work, the antitumor efficacy of photodynamic therapy for murine B16 melanoma with intravenous administration of a new photosensitizer (PS) based on the chlorin e6 conjugate with a prostate-specific membrane antigen (PSMA) was studied in vivo. We have previously published the data obtained in the first part of the study: the dynamics of PS accumulation in the tumor and surrounding tissues and the antitumor efficacy of the photodynamic therapy, which was evaluated by the regression parameters and morphological characteristics of the tumors—including by the complete regression of the tumors, the absolute growth rate of the tumors among the mice with continued tumor growth, and an increase in life expectancy compared to the control. The criterion for a complete cure was the absence of signs of tumor recurrence within 90 days after therapy. The conducted studies demonstrated the high efficiency of the new photosensitizer for the photodynamic therapy of B16 melanoma. This article presents a continuation of this work, including histological studies of the zones exposed to laser irradiation on the 21st day after treatment and an assessment of the therapeutic potential of photodynamic therapy for the destruction of tumor cells. Pathological studies in the zones of photodynamic exposure revealed that the effectiveness of the PDT depended on the PS dose and the laser irradiation parameters.

Photodynamic therapy in vulvar intraepithelial neoplasia (а review)

The authors discuss perspectives for applying photodynamic therapy (PDT) in patients with vulvar intraepithelial neoplasia (VIN); they also analyze domestic and foreign literature sources. Up to now, some experience on the treatment of background, precancerous conditions and vulvar cancer with PDT has been obtained. The authors describe application of various photosensitizers (5-aminolevulinic acid, hematoporphyrin, E6 chloride and others) as well as several techniques for photosensitizer administration and various parameters of photodynamic effect. PDT is a non-invasive modern curative option. This type of therapy has proven to be effective in many directions of medicine; it demonstrates a wide range of its potentials in antitumor, antimicrobial, antimycotic, antiviral, immunostimulating and many other effects. With PDT technique, one can preserve not only the function, but also the integrity of the organ; it gives an excellent cosmetic result as well as rapid recovery after the treatment. However, despite the low traumatic complication rate and low level of adverse reactions, data on PDT effectiveness are contradictory. In literature, there is a signififi cant range of set parameters for treatment and exposure modes from 50 to 350 J/cm2. Literature data demonstrate that PDT effectiveness in VIN treatment ranges from 30 to 95 %, while in some cases it reaches 100 %. So as to reliably assert PDT effectiveness in the discussed pathology, further research work is needed. This review analyzes other curative options, their advantages and disadvantages. The authors underline that effectiveness of other curative modalities is still low with a high rate of relapses.