Search Results (132)

The challenges associated with solubility and bioavailability of porphyrinoid-type photosensitizers in photodynamic therapy require solutions that are based on modern drug carriers, including polymeric nanoparticles. With that in mind this review discusses poly(lactic-co-glycolic acid, PLGA)-based polymeric nanoparticles encapsulating selected well-known photosensitizers, such as protoporphyrin IX, tetrahydroxyphenylporphyrin, chlorin e6, and tetracarboxyphenylporphyrin, with a view to the physicochemical and biological properties. Also discussed are their potential medical applications towards photodynamic and sonodynamic therapy. PLGA-based nanoparticles, encapsulating photosensitizers, were analysed in terms of particle size, surface charge, morphology, loading efficiency, release kinetics, and stability. Moreover, the cellular uptake and subcellular localisation of carriers were considered in correlation to polymer composition and surface functionalisation. Special attention was given to how PEGylation, lipid-hybrid coatings, or the incorporation of additional therapeutic or imaging agents has modulated both the physicochemical properties and biological activities of photosensitizers. The comparative assessment of different porphyrinoid-based photosensitizers highlighted how hydrophobicity, amphiphilicity, and molecular structure have an influence on encapsulation efficiency and therapeutic outcomes. Furthermore, issues such as the premature release of photosensitizers, along with limited bioavailability, and limited penetration through biological barriers were addressed as well as some proposed mitigation strategies. Overall, this review highlights the versatility of PLGA nanoparticles as a powerful platform for photosensitizer delivery, with promising implications for advancing polymer-based nanomedicine and improving the efficacy of photodynamic therapy. Full article

Gadolinium (Gd)-based nanomaterials have attracted a considerable amount of attention in cancer treatment research due to their applicability in radiotherapy. However, the clinical translation of Gd-based nanomaterials is limited by their high density and poor dispersibility in aqueous media, thereby necessitating surface functionalization with biocompatible polymers. In this study, gadolinium tungstate (Gd₂(WO₄)₃) nanoflakes (GW Nfs) were functionalized with poly(glycerol) (PG) to enhance their dispersibility and stability in aqueous media. Due to their high-Z elemental composition, the GW Nfs generated reactive oxygen species (ROS) under X-ray irradiation, with improved dispersibility induced by PG functionalization further enhancing ROS productivity compared to GW Nfs. Furthermore, PG-GW loaded with the photosensitizer chlorin e6 (Ce6) demonstrated strong photocytotoxicity at Ce6 concentrations as low as 0.2 μg mL⁻¹ under light irradiation. Taken together, these results demonstrate that PG-GW/Ce6 is a promising nanomaterial for photodynamic therapy while also offering prospects for bimodal photon cancer therapy with X-rays. Full article

Photosensitized excitation of molecular oxygen generates singlet oxygen, a reactive oxygen species that has been studied in biological systems, synthetic methods and in aquatic ecosystems. The reaction of singlet oxygen with tertiary amines is important because they are widely used as electron donors in photochemical reactions. Herein we studied the reaction of singlet oxygen with multiple tertiary amines including ethylenediamine tetraacetic acid (EDTA), triethanolamine (TEOA) and triethylamine (TEA). Singlet oxygen was generated using the photosensitizers methylene blue or chlorin e6 and red light with output at 660 nm. TEOA and TEA generated more hydrogen peroxide (H₂O₂), the stable end product, than EDTA at all pH values tested and regardless of the photosensitizer used. Both histidine and imidazole scavenged singlet oxygen and decreased H₂O₂ yield. The extent of histidine scavenging was pH-dependent for the combination of methylene blue and EDTA but not for TEOA or TEA. The combination of chlorin e6 and EDTA generated less H₂O₂ because both contain multiple negative charges that limit their interaction. Multiple tertiary amines that are used as biochemical buffers produced similar quantities of H₂O₂ as EDTA, TEOA and TEA. However, these sulfonic acid-containing tertiary amines did not function as electron donors in a benzoquinone photoreduction assay. Full article

Background/Objectives: Covalent conjugation of an antibiotic vancomycin (VCM) moiety and a photosensitizing mesochlorin (mChl_Pd) unit into one molecular entity may present the potential to produce the combinatorial effect of both antibacterial photodynamic therapeutic (aPDT) and antibiotic activities. Our recent study indicated that a short linkage of <4 (C−C/or C−N) bond distances between these two moieties resulted in significant steric hindrance due to the bulky VCM, which greatly reduces the accessibility of the agent to the cell surface of methicillin-resistant Staphylococcus aureus (MRSA). The observed aPDT efficacy was found to be minimal. Here, we report that the revision of this linkage, via an EG₁₀ unit using identical synthetic procedures, was able to resolve the issue. Methods: Accordingly, the corresponding combinatorial aPDT−antibiotic compound, consisting of two covalently bonded quaternary ammonium pentacationic arms on the mesochlorin chromophore core, designated as VCMe-mChl_Pd-N₁₀⁺ (LC40e⁺), was prepared for applications in antibacterial photodynamic inactivation (aPDI) activity. It was selected to investigate its enhanced binding and targeting ability to the surface of Gram-positive MRSA cells. Subsequent antibacterial photodynamic therapeutic (aPDT) activity to inactivate MRSA was investigated to substantiate the corresponding cell-surface binding effect on the efficacy of aPDT. Results: We found that the covalent combination of 10 positive charges and an MRSA-targeting vancomycin (VCM) moiety in a conjugated structure, functioning as an antibiotic–decacationic photosensitizing agent (Abx-dcPS), was capable of largely improving the MRSA cell-targeting efficiency. Importantly, variation in the chain length of the oligo(ethylene glycol) linker of VCMe-mChl_Pd-N₁₀⁺, which was sufficiently long enough to properly separate the photoactive mesochlorin ring moiety from the VCM moiety within the molecular structure, resulted in significantly enhanced aPDT activity. The new conjugate provided nearly complete eradication (>6.5-log₁₀ colony-forming units (CFU) reduction) of MRSA cells in vitro. The aPDT efficacy followed the order Abx-dcPS (combinatorial decacationic) > dcPS (decacationic) >> nPS (nonionic). This order was also verified by the relative physical binding trend of these PSs using either nPS-, dcPS-, or Abx-dcPS-pretreated and pre-fixed MRSA cells in investigations of fluorescent confocal microscopy, UV–vis fluorescence spectroscopy, and transmission electron microscopy (TEM). Conclusions: Furthermore, the molecular conjugate of Abx-dcPS may provide covalent co-delivery of two drug components concurrently, which might also serve as an effective antibiotic agent after aPDT and potentially prevent the reoccurrence of MRSA-induced infection. Full article

Despite advances in cancer treatment, head and neck squamous cell carcinoma (HNSCC) remains a serious clinical problem due to tumor aggressiveness, tumor resistance to therapy, and treatment toxicity. The combination of photodynamic therapy (PDT) with chemotherapy is a promising approach to improve efficacy while reducing side effects. For the first time, the possibility and antitumor effect of the combined use of PDT and chemotherapy with intra-arterial administration of chlorin e6 (Ce6) and cisplatin in patients with HNSCC were assessed. Two patients with locally advanced HNSCC received intra-arterial administration of Ce6 (at a dose of 0.5 mg/kg) and cisplatin (at a dose of 50 mg/m²) via a catheter into the tumor-feeding artery followed by laser irradiation. Ce6 distribution, tumor response, and treatment efficacy were assessed by fluorescence diagnostics, confocal microscopy, and histopathological analysis. Intra-arterial administration of the photosensitizer (PS) and chemotherapeutic agent ensured high selectivity of their tumor accumulation. Fluorescence diagnostics showed rapid and selective Ce6 accumulation in the tumor and PS photobleaching after PDT. For a patient with three PDT sessions, there is a significant acceleration of the Ce6 spread from the tumor-feeding artery throughout the tumor bed with each therapy session. This is a good sign of a tumor stroma density decrease. The combined use of PDT and chemotherapy with intra-arterial administration of Ce6 and cisplatin is safe and feasible, with preliminary evidence of local cytotoxicity treatment for HNSCC, allowing targeted drug delivery to the tumor. This is the first report of the combined use of PDT and chemotherapy with selective intra-arterial administration of a PS and a chemotherapeutic drug for the treatment of cancer. Full article

Photodynamic therapy (PDT) is a non-invasive therapeutic method with over a century of medical use, especially in dermatology, ophthalmology, dentistry, and, notably, cancer treatment. With an increasing number of clinical trials, there is growing demand for innovation in PDT. Despite being a promising treatment for cancer and bacterial infections, PDT faces limitations such as poor water solubility of many photosensitizers (PS), limited light penetration, off-target accumulation, and tumor hypoxia. This review focuses on chlorins—well-established macrocyclic PSs known for their strong activity and clinical relevance. We discuss how nanotechnology addresses PDT’s limitations and enhances therapeutic outcomes. Nanocarriers like lipid-based (liposomes, micelles), polymer-based (cellulose, chitosan, silk fibroin, polyethyleneimine, PLGA), and carbon-based ones (graphene oxide, quantum dots, MOFs), and nanospheres are promising platforms that improve chlorin performance and reduce side effects. This review also explores their use in Antimicrobial Photodynamic Therapy (aPDT) against multidrug-resistant bacteria and in oncology. Recent in vivo studies demonstrate encouraging results in preclinical models using nanocarrier-enhanced chlorins, though clinical application remains limited. Full article

An efficient protocol was developed for the microwave-mediated metallation of 5-(4-methoxycarbonylphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin (P1) with bis(benzonitrile)platinum dichloride salt and subsequent 1,3-dipolar cycloaddition of the resulting PtP1 with an azomethine ylide to give two isomeric metallochlorins: PtC1 (main isomer) and PtC3. The methyl ester group of metalloporphyrin PtP1 and metallochlorin PtC1 was successfully hydrolysed in an alkaline medium to yield the corresponding derivatives PtP2 and PtC2 in moderate-to-good yields. As a proof of concept of the reactivity of the carboxy group in PtP2 and PtC2, these compounds were conjugated with a hydroxylated derivative of indomethacin, a known potent non-steroidal anti-inflammatory, obtaining the conjugates PtP2-Ind and PtC2-Ind. The obtained platinum(II) porphyrins and chlorins were characterized by UV-Vis, NMR spectroscopy and mass spectrometry. The structure of PtP1 was also confirmed by X-ray crystallography. Singlet oxygen generation studies were carried out, as well as theoretical calculations, which demonstrated that the prepared Pt(II) complexes can be considered potential photosensitizers for PDT. Full article

In this article, the synthesis and characterization of chlorin-based photosensitizers for potential applications in photodynamic therapy (PDT) of triple-negative breast cancer (TNBC) are described. The photodynamic efficacy of the synthesized chlorin-desthiobiotin (CDBTN) conjugate and its zinc and indium complexes were compared with the starting unconjugated precursor methyl pheophorbide, and assessed in a TNBC cell line in vitro. The chlorin-desthiobiotin complex aims to target the vitamin receptors upregulated in malignant cancer cells. The synthesized CDBTN was combined with chemotherapeutic agents (paclitaxel, cisplatin or fluorouracil) to evaluate their binary photodynamic efficacy. Cell survival assay in vitro indicated that the chlorin-vitamin conjugate CDBTN—alone and in combination with paclitaxel or fluorouracil—is photoactive against the TNBC cell line, but not when combined with cisplatin. The combination index (CI) calculated using the Chou-Talalay method indicated synergism of CDBTN and fluorouracil combination, aligning with the in vitro assay. The photodynamic cytotoxicity of CDBTN was also evaluated in vivo using the hydra as a novel model organism. This study is the first to show the use of the aquatic hydra organism in assessing photodynamic activity of the photosensitizer alone or in combination with chemotherapeutic agents. In vivo results with hydras indicated that the CDBTN-cisplatin combination is more phototoxic than CDBTN-paclitaxel or CDBTN-fluorouracil binary treatment. With the proper adjustment of concentration and light dosage, the synthesized photosensitizer can provide promising application in binary chemotherapy PDT treatment of TNBC. Full article

In recent years, chemo-photodynamic combinational therapy has become increasingly popular in treating breast cancer. However, the limited accumulation of nanodrugs into tumors (less than 1% of the injected dose) impacts therapeutic efficacy to an extreme extent. Herein, the photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug rhein were self-assembled to form a carrier-free nanodrug (RC NPs) with good stability and a high drug loading rate (nearly 100%). In vitro, the phototoxicity of RC NPs resulted in a mere 17.8% cell viability. Ultrasound (US) irradiation was applied to increase the permeability of tumor blood vessels, thus greatly enhancing the drug accumulation of RC NPs in tumor tissues (1.5 times that of the control group). After uptake by tumor cells, Ce6 could produce a significant amount of reactive oxygen species (ROS) when exposed to laser irradiation, while rhein could inhibit tumor cell proliferation and affect mitochondrial membrane potential, inducing tumor cell apoptosis through the mitochondria-dependent apoptosis pathway, thus effectively realizing the combined effect of PDT and chemotherapy. The final tumor inhibition rate reached 93.7%. Taken together, RC NPs strengthen the enhanced permeability and retention (EPR) effect when exposed to US irradiation and exhibit better tumor suppression, which provides new insights into chemo-photodynamic combination treatment for clinical breast cancer. Full article

Background: Globally, colorectal cancer (CRC) is the third-most diagnosed cancer among males and the second-most diagnosed cancer among females. In cancer, stem cells are a subset of neoplastic cells capable of tumorigenesis and exhibit properties like normal stem cells. Moreover, they are resistant to conventional cancer treatments and can repopulate the tumor following treatment. Cancer cells are stimulated to undergo apoptosis by photodynamic therapy (PDT), which involves a light source, a photosensitizer, and reactive oxygen species. Methods: In this study, colon cancer stem cells were isolated from colon cancer cells and characterized using flow cytometry and immunofluorescence techniques. To treat colon cancer stem cells (CCSCs), single-walled carbon nanotubes (SWCNTs) were coupled with hyaluronic acid (HA) and loaded with chlorin-e6 (Ce6). Nanobiocomposite toxicity was assessed using CCSCs with two fluences of 5 J/cm² and 10 J/cm². The cellular changes were observed at 24 and 48 h using microscopy, Results: LDH cytotoxicity assay, and cell death induction by annexin propidium iodide assay. An intracellular analysis of reactive oxygen species (ROS) detected oxidative stress within CCSCs. Conclusions: Overall, the results showed that the newly synthesized nanobiocomposite enhanced the ability of PDT to act as a photosensitizer carrier and induced cell death in CCSCs. Full article

Oral potentially malignant disorders (OPMDs) are conditions that carry an increased risk of malignant transformation, including oral leukoplakia and oral lichen planus. Current management approaches differ based on each condition’s unique etiology and pathophysiology, but all available treatment methods have notable limitations. This has prompted continued efforts to identify more effective therapeutic options. Photodynamic therapy (PDT) has emerged as a minimally invasive yet potent alternative for treating OPMDs. This systematic review examines the efficacy of PDT mediated by toluidine blue and chlorin-e6 (Photolon) in managing OPMDs. Following the PRISMA guidelines, eight relevant studies published between 2010 and 2024 were included. Data on the study design, protocols, light parameters, and photosensitizer characteristics were collected to evaluate treatment outcomes. The reviewed evidence suggests that toluidine-blue- and chlorin-e6-mediated PDT holds promise as a minimally invasive treatment modality for OPMDs, especially for oral lichen planus and oral leukoplakia. Studies indicate its potential as an alternative or adjunct therapy, particularly for symptomatic or refractory oral lichen planus. However, discrepancies in study designs and treatment protocols, coupled with the limited number of trials, impeded direct comparisons. Toluidine-blue- and chlorin-e6-mediated PDT shows significant potential as a therapeutic option for OPMDs. Nonetheless, further investigations—including large-scale randomized controlled trials, standardized treatment guidelines, and the exploration of additional OPMDs beyond oral lichen planus and oral leukoplakia—are necessary in order to fully establish its clinical utility and facilitate widespread adoption. Full article

Background/Objectives: Glioblastoma (GBM) is the deadliest type of brain tumor and photodynamic therapy (PDT) is a promising treatment modality of GBM. However, insufficient photosensitizer distribution in the GBM critically limits the success of PDT. To address this obstacle, we propose tumoritropic neutrophils (NE) as active carriers for photosensitizer delivery to achieve GBM-targeted PDT. Methods: Isolated mouse NE were loaded with functionalized hexagonal boron nitride nanoparticles carrying the photosensitizer chlorin e6 (BNPD-Ce6). In vitro experiments were conducted to determine drug release from the loaded NE (BNPD-Ce6@NE) to mouse GBM cells and consequential photo-cytotoxicity. In vivo experiments were performed on mice bearing intracranial graft GBMs to demonstrate GBM-targeted drug delivery and the efficacy of anti-GBM PDT mediated by BNPD-Ce6@NE. Results: BNPD-Ce6@NE displayed good viability and migration ability, and rapidly released BNPD-Ce6 to co-cultured mouse GBM cells, which then exhibited marked reactive oxygen species (ROS) generation and cytotoxicity following 808 nm laser irradiation (LI). In the in vivo study, a single intravenous bolus injection of BNPD-Ce6@NE resulted in pronounced Ce6 distribution in intracranial graft GBMs 4 h post injection, which peaked around 8 h post injection. A PDT regimen consisting of multiple intravenous BNPD-Ce6@NE injections each followed by one extracranial tumor-directed LI 8 h post injection significantly slowed the growth of intracranial graft GBMs and markedly improved the survival of host animals. Histological analysis revealed massive tumor cell damage and NE infiltration in the PDT-treated GBMs. Conclusions: NE are efficient carriers for GBM-targeted photosensitizer delivery to achieve efficacious anti-GBM PDT. Full article

The photosensitizer (PS) in the Photodynamic Therapy (PDT) field represents a key factor, being directly connected to the therapeutic efficacy of the process. Chlorin e6 is a second-generation photosensitizer, approved by the FDA with the most desired clinical properties for PDT applications, presenting high reactive oxygen species (ROS) generation and proven anticancer properties. However, hydrophobicity is a major limitation, leading to poor biodistribution. To overcome this condition, the present work developed an up-to-date nanoemulsion incorporating Ce6 in a new nanosystem (Ce6/NE). A comprehensive study of physicochemical properties, stability, fluorescence characteristics, the in vitro release profile, in vivo and ex vivo biocompatibility, and ex vivo efficacy was established. The nanoemulsions showed the desired particle size and stability over six months, with no spectroscopic or photophysical alterations. Uptake studies demonstrated the internalization of the Ce6/NE in monolayers, with biocompatibility at the lowest concentrations. The HET-CAM assay, however, revealed a higher biocompatibility range, also indicating Ce6/NE’s potential for cancer treatment through antiangiogenic studies. These findings highlight the use of a new promising photosensitizer for PDT modulated with nanotechnology that promotes low toxicity, higher bioavailability, and site-specific delivery. Full article

The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with the amine group of chitosan oligosaccharide (COS) using a thioketal linker (COSthBSO) to liberate BSO and chlorine e6 (Ce6) under oxidative stress, and then, Ce6-COSthBSO NP (Ce6-COSthBSO NP), fabricated by a dialysis procedure, showed an accelerated release rate of BSO and Ce6 by the addition of hydrogen peroxide, indicating that nanophotosensitizers have ROS sensitivity. In the in vitro cell culture study using HCT116 colon carcinoma cells, a combination of BSO and Ce6 efficiently suppressed the intracellular GSH and increased ROS production compared to the sole treatment of Ce6. In particular, Ce6-COSthBSO NP showed higher efficacy in the suppression of GSH levels and ROS production compared to the free Ce6 and Ce6/BSO combination. These results were due to the fact that Ce6-COSthBSO NP was efficiently delivered to the intracellular region, suppressed intracellular GSH levels, and elevated ROS levels. The in vivo animal tumor xenograft study demonstrated Ce6-COSthBSO NP being efficiently delivered to the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was higher than those of other organs. The combination of Ce6 and BSO efficiently suppressed tumor growth compared to the sole treatment of Ce6, indicating that BSO might efficiently suppress GSH levels and increase ROS levels in the tumor microenvironment. Specifically, Ce6-COSthBSO NP showed the strongest performance in inhibition of tumor growth than those of Ce6 or the CE6/BSO combination, indicating that they were efficiently delivered to tumor tissue, increased ROS levels, and then efficiently inhibited tumor growth. We suggest that COSthBSO nanophotosensitizers are promising candidates for PDT treatment of cancer cells. Full article

Oral squamous cell carcinoma (OSCC) is a common malignancy in the oral cavity. Photodynamic therapy (PDT) is a new alternative for the treatment of diseases using photosensitizers (PS) and light. In this study, we used a photosensitizer complex (Ce6-MnNPs—Chlorin e6 combined with up-conversion nanoparticles NaYF₄:Yb/Er/Mn) to investigate the therapeutic effectiveness of this treatment against oral cancer cells. We also investigated the mechanism of action of near-infrared light PDT (NIR-PDT) combined with the Ce6-MnNPs. After determining a suitable concentration of Ce6-MnNPs using an MTT assay, human oral squamous cell carcinoma cells (HSC-3) were treated with NIR-PDT with Ce6-MnNPs. We examined the characteristics of Ce6-MnNPs by transmission electron microscopy (TEM); a zeta potential and particle size analyzer; Fourier-transform infrared spectroscopy (FTIR); cell viability by MTT assay; and apoptosis by FITC-Annexin V/PI assay. The mitochondrial membrane potential (MMP), apoptosis-related mRNA level (Bax and Bcl-2) and p53 protein were also researched. NIR-PDT with 0.5 ng/µL Ce6-MnNPs inhibited the proliferation of HSC-3 (p < 0.05). After treatment with NIR-PDT, changes in the mitochondrial membrane potential and apoptosis occurred (p < 0.01). The ratio of Bax/Bcl-2 and p53-positive cells increased (p < 0.01). These results suggest that this treatment can induce apoptosis of oral cancer cells. Full article