Advances In Photodynamic Therapy Research Articles

Recent Advances in Photodynamic Therapy for Vascular Abnormalities.

Abstract Background: Photodynamic therapy (PDT) is a minimally invasive therapy that was gradually established as a first-line treatment for vascular abnormalities. Its action depends on the appropriate wavelength of light and photosensitizer to produce toxic oxygen species and cause cell death. Objective: Several new clinical improvements and trends in PDT have been described in recent years. The aim of this review is to provide an overview of the current data from clinical trials. Methods: In this review, we introduce and generalize the wavelength, duration, dose, strength, and photosensitizer of PDT for the treatment of vascular abnormalities, such as circumscribed choroidal hemangiomas (CCH), choroidal neovascularization (CNV) and capillary malformation (CM). Results: The systematic review findings indicate that the application of PDT is a safe effective method to treat CCH, CNV and CM. However, PDT also has early onset side effects and late onset side effects. Conclusions: Based on the discussion of the effectiveness of PDT, we conclude that PDT has great potential for clinical use, although PDT has possible side effects.

The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy.

Lipids, together with lipoprotein particles, are the cause of atherosclerosis, which is a pathology of the cardiovascular system. In addition, it affects inflammatory processes and affects the vessels and heart. In pharmaceutical answer to this, statins are considered a first-stage treatment method to block cholesterol synthesis. Many times, additional drugs are also used with this method to lower lipid concentrations in order to achieve certain values of low-density lipoprotein (LDL) cholesterol. Recent advances in photodynamic therapy (PDT) as a new cancer treatment have gained the therapy much attention as a minimally invasive and highly selective method. Photodynamic therapy has been proven more effective than chemotherapy, radiotherapy, and immunotherapy alone in numerous studies. Consequently, photodynamic therapy research has expanded in many fields of medicine due to its increased therapeutic effects and reduced side effects. Currently, PDT is the most commonly used therapy for treating age-related macular degeneration, as well as inflammatory diseases, and skin infections. The effectiveness of photodynamic therapy against a number of pathogens has also been demonstrated in various studies. Also, PDT has been used in the treatment of cardiovascular diseases, such as atherosclerosis and hyperplasia of the arterial intima. This review evaluates the effectiveness and usefulness of photodynamic therapy in cardiovascular diseases. According to the analysis, photodynamic therapy is a promising approach for treating cardiovascular diseases and may lead to new clinical trials and management standards. Our review addresses the used therapeutic strategies and also describes new therapeutic strategies to reduce the cardiovascular burden that is induced by lipids.

Advances in Photodynamic Therapy for Central-type Lung Cancer: Clinical Outcomes and Adverse Events

Advances in Photodynamic Therapy for Central-type Lung Cancer: Clinical Outcomes and Adverse Events

Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies.

Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous and precancerous cell death after light activation (phototoxicity). The biophysical, bioengineering aspects and its combinations with other strategies are highlighted in this review, both conceptually and as they are currently applied clinically. We further explore the recent advancements of PDT with the use of nanotechnology, including quantum dots as innovative photosensitizers or energy donors as well as the combination of PDT with radiotherapy and immunotherapy as future promising cancer treatments. Finally, we emphasize the potential significance of organoids as physiologically relevant models for PDT.

Hyperbranched Polymers: Recent Advances in Photodynamic Therapy against Cancer.

Hyperbranched polymers are a class of three-dimensional dendritic polymers with highly branched architectures. Their unique structural features endow them with promising physical and chemical properties, such as abundant surface functional groups, intramolecular cavities, and low viscosity. Therefore, hyperbranched-polymer-constructed cargo delivery carriers have drawn increasing interest and are being utilized in many biomedical applications. When applied for photodynamic therapy, photosensitizers are encapsulated in or covalently incorporated into hyperbranched polymers to improve their solubility, stability, and targeting efficiency and promote the therapeutic efficacy. This review will focus on the state-of-the-art studies concerning recent progress in hyperbranched-polymer-fabricated phototherapeutic nanomaterials with emphases on the building-block structures, synthetic strategies, and their combination with the codelivered diagnostics and synergistic therapeutics. We expect to bring our demonstration to the field to increase the understanding of the structure-property relationships and promote the further development of advanced photodynamic-therapy nanosystems.

Photodynamic Therapy in Oral Cancer: A Narrative Review.

Methods: A comprehensive search in PubMed, Scopus, and Google Scholar was performed using relevant keywords to structure this narrative review. Only English articles were included and assessed according to titles, abstracts, and full texts. Background: Photodynamic therapy (PDT) is applied for targeting pre-malignancy and malignancies in the head and neck, skin, lungs, and gastrointestinal tract and has been greatly promising in reducing disfigurement and morbidity. This method includes a light-sensitive medicine known as a photosensitizer and a light source used through a minimally invasive surgical tool. Objective: This study aimed to review the application of PDT in managing head and neck cancers (HNCs) and provide an overview of the most recent advances in PDT and its efficiency in increasing the long-term life quality of patients with HNC. Results: The light source irradiates light at an appropriate wavelength that can be absorbed by the sensitizer and produce cytotoxic free radicals that can kill tumor cells, impair microvasculature in the tumor microenvironment, and stimulate further inflammatory responses of the immune system. Patients with either early lesions or advanced disease conveniently accept to receive PDT in outpatient clinics. Therefore, this simple technique is considered a novel and promising approach that can be used either individually or in association with other methods. However, its application as a management method in oral malignancies has yet to be studied. PDT is also suggested as a promising adjuvant treatment with better functional results. Then, it is possible to conclude that PDT's effectiveness in treating various tumors has been shown to depend on the depth of the lesion location. Its safety is acceptable, but its limited irradiation depth confines its application in the advanced stages of cancer. Conclusions: PDT is critically applicable in the early diagnosed cancers and superficial tumors where many heads and neck lesions settle as an ideal candidate for PDT because of the possibility of accurate evaluation of lesions and providing appropriate irradiation at these sites.

Photodynamically inactive prodrug based-on leuco-BODIPY: In vivo tumor targeting and microenvironment activated photodynamic therapy

• The pro-photosensitizer predominantly keeps photodynamically inactive in the vasculature at pH 7.4. • The pro-photosensitizer transforms into a conjugated BODIPY photosensitizer by tumor-associated acidic extracellular matrix (pH 6.5–6.8) and lysosomes (pH 4.5-5.5). • Pro-photosensitizer with tumor-targeting moieties allows the prodrug to target tumor tissues. • A reversible interconversion between photosensitizer and pro-photosensitizer. Recent advances in photodynamic therapy (PDT) require the selective sensitization of the targeted disease to avoid undesired side effects. The development of photosensitizers that are photodynamically silent until reaching their respective target is one of the most promising strategies to avoid background accumulation in non-target tissue. Here, we report a colorless/nonconjugated leuco-BODIPY pro-1 covalently linked to targeting tumor-associated polyamine substituent. Pro-1 predominantly keeps photodynamically inactive in the vasculature at pH 7.4. After targeting the elevated polyamine transporters in neoplastic cells, pro-1 transforms into a conjugated BODIPY photosensitizer 1 by tumor-associated acidic extracellular matrix (pH 6.5–6.8) and the neoplastic increased abundance of lysosomes (pH 4.5–5.5). The phototoxicity of 1 effectively inhibits the growth of tumors (86% by volume) on tumor-bearing mice. More importantly, during the PDT treatment, photosensitizer 1 remains the leuco-BODIPY form in the vascular system and the extracellular matrix of normal tissues, reducing the side effect of long-lasting photosensitivity.

Advances in Photodynamic Therapy for the Treatment of Actinic Keratosis and Nonmelanoma Skin Cancer: A Narrative Review.

Photodynamic therapy (PDT) with photosensitization using 5-aminolevulinic acid (ALA) [including a nanoemulsion (BF-200 ALA)] is approved in the USA for the treatment of actinic keratoses (AKs); another derivative, methyl aminolevulinate, is not approved in the USA but is used in Europe. For AK treatment, the photosensitizer may be applied to individual AK lesions or, depending on treatment regimen, to broader areas of sun-damaged skin to manage field cancerization, although not all products are approved for field treatment. ALA-PDT and photosensitizers have also been used off-label for the treatment of nonmelanoma skin cancers, primarily basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCC). Advantages of PDT include potentially improved cosmesis and patient satisfaction; disadvantages include pain and duration of treatment. Alternative illumination approaches, including intense pulsed light as well as pulsed-dye lasers, have also been used successfully. Pretreating the affected tissue or warming during incubation can help to increase photosensitizer absorption and improve therapeutic efficacy. Combinations of multiple treatments are also under exploration. Reducing incubation time between photosensitizer application and illumination may significantly reduce pain scores without affecting treatment efficacy. Substituting daylight PDT for a conventional illumination source can also reduce pain without compromising efficacy. The objective of this narrative review is to describe current and ongoing research in the use of topical photosensitizers and modified light delivery regimens to achieve improved therapeutic outcomes with less toxicity in patients with AK, cSCC, BCC, and field cancerization.

Applications of supramolecular assemblies in drug delivery and photodynamic therapy.

One of the world's serious health challenges is cancer. Anti-cancer agents delivered to normal cells and tissues pose several problems and challenges. In this connection, photodynamic therapy (PDT) is a minimally invasive therapeutic technique used for selectively destroying malignant cells while sparing the normal tissues. Development in photosensitisers (PSs) and light sources have to be made for PDT as a first option treatment for patients. In the pursuit of developing new attractive molecules and their formulations for PDT, researchers are working on developing such type of PSs that perform better than those being currently used. For the widespread clinical utilization of PDT, effective PSs are of particular importance. Host-guest interactions based on nanographene assemblies such as functionalized hexa-cata-hexabenzocoronenes, hexa-peri-hexabenzocoronenes and coronene have attracted increasing attention owing to less complicated synthetic steps and purification processes (gel permeation chromatography) during fabrication. Noncovalent interactions provide easy and facile approaches for building supramolecular PSs and enable them to have sensitive and controllable photoactivities, which are important for maximizing photodynamic effects and minimizing side effects. Various versatile supramolecular assemblies based on cyclodextrins, cucurbiturils, calixarenes, porphyrins and pillararenes have been designed in order to make PDT an effective therapeutic technique for curing cancer and tumours. The supramolecular assemblies of porphyrins display efficient electron transfer and fluorescence for use in bioimaging and PDT. The multifunctionalization of supramolecular assemblies is used for designing biomedically active PSs, which are helpful in PDT. It is anticipated that the development of these functionalized supramolecular assemblies will provide more fascinating advances in PDT and will dramatically expand the potential and possibilities in cancer treatments.

Photodynamic therapy in breast cancer treatment.

Breast cancer is a serious public problem in modern society. Photodynamic therapy (PDT) is increasingly used in modern medicine. Currently, PDT is an innovative method of treating breast cancer. Irreversible damage to neoplastic tissues is associated with the use of physicochemical processes. Generating cytotoxic reactive oxygen species [singlet oxygen (1O2)] is leading to tumor cell death. At the same time, valuable information can be extracted from breast cancer cells. Photogenerated 1O2 is the major factor responsible for cell necrosis during PDT. 1O2 can react rapidly intracellularly with all organic substances. The use of photodynamic therapy on tissues in vitro creates conditions for testing various types of solutions and implementing them in in vivo treatment. This article is a review of recent advances in PDT for treatment of breast cancer. PDT is a novel cancer diagnostic and cancer treatment therapy. Therefore, an understanding of the possibility to generate a toxic form of 1O2 is necessary. The knowledge gained from the basics of PDT in vitro can be useful in biomedical applications in vivo. The current literature mentions PDT in the treatment of cancers located very deep within the human body. Therefore, the development of agents used to deliver 1O2 to the deep cancerous tissue is a new challenge which can have an efficient impact on this discipline. This review covers the literature between 2000-2022.

Advances in Photodynamic Therapy Based on Nanotechnology and Its Application in Skin Cancer.

Comprehensive cancer treatments have been widely studied. Traditional treatment methods (e.g., radiotherapy, chemotherapy), despite ablating tumors, inevitably damage normal cells and cause serious complications. Photodynamic therapy (PDT), with its low rate of trauma, accurate targeting, synergism, repeatability, has displayed great advantages in the treatment of tumors. In recent years, nanotech-based PDT has provided a new modality for cancer treatment. Direct modification of PSs by nanotechnology or the delivery of PSs by nanocarriers can improve their targeting, specificity, and PDT efficacy for tumors. In this review, we strive to provide the reader with a comprehensive overview, on various aspects of the types, characteristics, and research progress of photosensitizers and nanomaterials used in PDT. And the application progress and relative limitations of nanotech-PDT in non-melanoma skin cancer and melanoma are also summarized.

Recent Advances in Photodynamic Therapy against Fungal Keratitis.

Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.

Recent Advances in Photodynamic Therapy for Deep-Seated Tumors with the Aid of Nanomedicine.

Photodynamic therapy (PDT) works through photoactivation of a specific photosensitizer (PS) in a tumor in the presence of oxygen. PDT is widely applied in oncology to treat various cancers as it has a minimally invasive procedure and high selectivity, does not interfere with other treatments, and can be repeated as needed. A large amount of reactive oxygen species (ROS) and singlet oxygen is generated in a cancer cell during PDT, which destroys the tumor effectively. However, the efficacy of PDT in treating a deep-seated tumor is limited due to three main reasons: Limited light penetration depth, low oxygen concentration in the hypoxic core, and poor PS accumulation inside a tumor. Thus, PDT treatments are only approved for superficial and thin tumors. With the advancement of nanotechnology, PDT to treat deep-seated or thick tumors is becoming a reachable goal. In this review, we provide an update on the strategies for improving PDT with nanomedicine using different sophisticated-design nanoparticles, including two-photon excitation, X-ray activation, targeting tumor cells with surface modification, alteration of tumor cell metabolism pathways, release of therapeutic gases, improvement of tumor hypoxia, and stimulation of host immunity. We focus on the difficult-to-treat pancreatic cancer as a model to demonstrate the influence of advanced nanomedicine in PDT. A bright future of PDT application in the treatment of deep-seated tumors is expected.

Update on dermatologic laser therapy II - advances in photodynamic therapy using laser-assisted drug delivery.

Technical advances in recent years have led to the development of new dermatologic laser systems, light sources, and treatment concepts. With the introduction of ablative fractional lasers (using common wavelengths) in the field of dermatology, it is now possible to more effectively and efficiently treat a variety of skin disorders. One important example of these advances is laser-assisted drug delivery (LADD). A type of LADD, laser-assisted photodynamic therapy has been successfully employed in the treatment of non-melanoma skin cancer including field cancerization. This treatment concept has been continually modified and today includes the use of daylight as well as artificial daylight systems. This update is based as cited, shortened and updated according to "Paasch,U. 2019. Laser-assistierte photodynamische Therapie. p. 226-239. In G.Kautz (ed.) Energie für die Haut. Springer Nature, Springer Nature".

Recent advances in photodynamic therapy based on emerging two-dimensional layered nanomaterials

Photodynamic therapy (PDT) is a promising non-invasive therapy approach for various diseases including malignant tumor. The process of PDT involves three interrelated aspects, namely photosensitizer (PS), light source, and oxygen, among which PS is the decisive factor that determines its anticancer efficiency. There exist some defects in currently applied PDT, such as inadequate production of reactive oxygen species (ROS), poor penetration of exciting light, insufficient oxygen supply, and nonselective distribution of PS. With unique physicochemical and optical properties, two-dimensional nanomaterials (2DNMs) have aroused great interest in biomedical fields. 2DNMs-based PDT is promising to significantly improve antitumor efficacy compared to conventional PDT. In this review, we will firstly introduce the underlying mechanism of PDT and how 2DNMs are absorbed and distribute inside tumor cells. After that, we will not only illustrate how 2DNMs-based PDT can enhance tumor-killing efficacy and minimize side-effects through conquering the above-mentioned defects of conventional PDT and the preparation process of 2DNMs, but also elaborate recent advances about 2DNMs-based PDT. Lastly, we will summarize the challenges and future prospects of 2DNMs-based PDT.

Construction of microneedle-assisted co-delivery platform and its combining photodynamic/immunotherapy

Despite advances in photodynamic therapy (PDT) for treating superficial tumor, the prospect of this monotherapy remains challenges in the context of systemic phototoxicity and poor efficacy. In this work, a physiologically self-degradable microneedle (MN)-assisted platform is developed for combining PDT and immunotherapy via controlled co-delivery of photosensitizer (PS) and checkpoint inhibitor anti-CTLA4 antibody (aCTLA4), which generates synergistic reinforcement outcome while reducing side effects. MN is composed of biocompatible hyaluronic acid integrated with the pH-sensitive dextran nanoparticles, which is fabricated to simultaneously encapsulate hydrophobic (Zinc Phthalocyanine) and hydrophilic agents (aCTLA4) via a double emulsion method. This co-loading carrier can aggregate effectively around topical tumor by microneedle-assisted transdermal delivery. In vivo studies using 4T1 mouse models, PDT firstly exerts its effect to killing tumor and triggers the immune responses, subsequently, facilitating the immunotherapy with immune checkpoint inhibitor (aCTLA4). The possible mechanism and systemic effects of the combined therapy are investigated, which demonstrate that this co-administration platform can be a promising tool for focal cancer treatment.

Photodynamic Therapy Based on Graphene and MXene in Cancer Theranostics.

Cancer is one of the leading causes of death in the world. Therefore, the development of new advanced and targeted strategies in cancer research for early diagnosis and treatment has become essential to improve diagnosis outcomes and reduce therapy side effects. Graphene and more recently, MXene, are the main representatives of the family of two-dimensional (2D) materials and are widely studied as multimodal nanoplatforms for cancer diagnostics and treatment, in particular leveraging their potentialities as photodynamic therapeutic agents. Indeed, due to their irreplaceable physicochemical properties, they are virtuous allies for photodynamic therapy (PDT) in combination with bioimaging, photothermal therapy, as well as drug and gene delivery. In this review, the rapidly progressing literature related to the use of these promising 2D materials for cancer theranostics is described in detail, highlighting all their possible future advances in PDT.

Photodynamic therapy for solid tumors: A review of the literature.

Photodynamic therapy (PDT) utilizes a sensitizer agent and light to produce selective cell death. Dermatologists are familiar with PDT for the treatment of actinic keratoses and early nonmelanoma skin cancers, and recent studies have elucidated that PDT has resulted in improved morbidity and secondary outcomes for the treatment of various cancerous and precancerous solid tumors. Light source and dosimetry may be modified to selectively target tissue, and novel techniques such as fractionation, metronomic pulsation, continuous light delivery, and chemophototherapy are under investigation for further optimization of therapy. This article aims to review the expanding indications for PDT and demonstrate the potential of this modality to decrease morbidity and increase quality of life for patients. To illustrate these new indications, we provide a focused review of the latest literature on PDT for dermatologic and other solid tumors including gastrointestinal, peritoneal, lung, genitourinary, brain, breast, and head and neck. Data on efficacy, survival, and side effects vary across tumor types but support PDT for the treatment of numerous solid tumors. With new advances in PDT, indications for this therapeutic modality may expand.

Recent advances in photodynamic therapy for cancer and infectious diseases.

Photodynamic therapy (PDT) is a treatment by combining light and a photosensitizer to generate reactive oxygen species (ROS) for cellular damage, and is used to treat cancer and infectious diseases. In this review, we focus on recent advances in design of new photosensitizers for increased production of ROS and in genetic engineering of biological photosensitizers to study cellular signaling pathways. A new concept has been proposed that PDT-induced acute inflammation can mediate neutrophil infiltration to deliver therapeutics in deep tumor tissues. Combination of PDT and immunotherapies (neutrophil-mediated therapeutic delivery) has shown the promising translation of PDT for cancer therapies. Furthermore, a new area in PDT is to treat bacterial infections to overcome the antimicrobial resistance. Finally, we have discussed the new directions of PDT for therapies of cancer and infectious diseases. In summary, we believe that rational design and innovations in nanomaterials may have a great impact on translation of PDT in cancer and infectious diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

RGD-Modified Albumin Nanoconjugates for Targeted Delivery of a Porphyrin Photosensitizer.

Advances in photodynamic therapy of cancer have been restrained by lack of cancer specificity and side effects to normal tissues. Molecularly targeted photodynamic therapy can achieve higher cancer specificity by combination of active cancer targeting and localized laser activation. We aimed to use albumin as a carrier to prepare targeted nanoconjugates that are selective to cancer cells and smaller than conventional nanoparticles for superior tumor penetration. IRDye 700DX (IR700), a porphyrin photosensitizer, was covalently conjugated to human serum albumin that was also linked with tumor-targeting RGD peptides. With multiple IR700 and RGD molecules in a single albumin molecule, the resultant nanoconjugates demonstrated monodispersed and uniform size distribution with a diameter of 10.9 nm. These targeted nanoconjugates showed 121-fold increase in cellular delivery of IR700 into TOV21G ovarian cancer cells compared to control nanoconjugates. Mechanistic studies revealed that the integrin specific cellular delivery was achieved through dynamin-mediated caveolae-dependent endocytosis pathways. They produced massive cell killing in TOV21G cells at low nanomolar concentrations upon light irradiation, while NIH/3T3 cells that do not express integrin αvβ3 were not affected. Because of their small size, targeted albumin nanoconjugates could penetrate tumor spheroids of SKOV-3 ovarian cancer cells and produced strong phototoxicity in this 3-D model. Owing to their cancer-specific delivery and small size, these targeted nanoconjugates may become an effective drug delivery system for enabling molecularly targeted photodynamic therapy of cancer.