Efficacy Of Photodynamic Treatment Research Articles

Enhancing Surface Hydroxyl Group Modulation on Carbon Nitride Boosts the Effectiveness of Photodynamic Treatment for Brain Glioma.

The effectiveness of photodynamic therapy (PDT) in treating brain gliomas is limited by the solubility of photosensitizers and the production of reactive oxygen species (ROS), both of which are influenced by the concentration of photosensitizers and catalyst active sites. In this study, we developed a controllable surface hydroxyl concentration for the photosensitizer CN11 to address its poor water solubility issue and enhance PDT efficacy in tumor treatment. Compared to pure g-C3N4 (CN), CN11 exhibited 4.6 times higher hydrogen peroxide production under visible light, increased incidence of the n → π* electron transition, and provided more available reaction sites for cytotoxic ROS generation. These findings resulted in a 2.43-fold increase in photodynamic treatment efficacy against brain glioma cells. Furthermore, in vivo experiments conducted on mice demonstrated that CN11 could be excreted through normal cell metabolism with low cytotoxicity and high biosafety, effectively achieving complete eradication of tumor cells.

Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Photoinduced Toxicity Caused by Gold Nanozymes and Photodynamic Dye Encapsulated in Submicron Polymer Shell

AbstractThe development of nanozymes, artificial enzymes made from inorganic nanoparticles, is widely studied due to their affordability, durability, and strength. Gold nanoparticles (AuNPs) are employed to imitate peroxidase, glucose oxidase, lactate oxidase, superoxide dismutase, and catalase. The last one transforms intracellular hydrogen peroxide into molecular oxygen, whose deficiency is characteristic of the hypoxic tumor microenvironment. Thus, gold nanoparticles are thought to enhance the overall effectiveness of photodynamic therapy. However, the enzyme‐like activity of nanoparticles rapidly decreases in biological media, due to the aggregation and formation of the so‐called “protein corona”. In this study, polymeric submicrocapsules loaded with AuNPs and a photodynamic dye are fabricated via Layer‐by‐Layer (LbL) assembly. The enhancement of photodynamic treatment efficacy by in situ production of oxygen by the catalase‐like effect of AuNPs is investigated. Polymeric capsules are thoroughly characterized in terms of physicochemical and catalytic properties, and as a proof of concept, their therapeutic potential is evaluated in vitro. Furthermore, encapsulated AuNPs shows significantly lower aggregation both upon storage and during the reaction course. The results shows that the polymer capsules, containing AuNPs and photodynamic dye, show significantly higher light‐induced cytotoxicity in comparison to the individual photodynamic dye, suggesting a synergistic effect between the formation of molecular oxygen by catalase‐like gold nanozymes and photodynamic action.

DNase improves the efficacy of antimicrobial photodynamic therapy in the treatment of candidiasis induced with Candida albicans.

The study evaluated the association of DNase I enzyme with antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in mice infected with fluconazole-susceptible (CaS) and -resistant (CaR) Candida albicans strains. Mice were inoculated with C. albicans, and after the infection had been established, the tongues were exposed to DNase for 5 min, followed by photosensitizer [Photodithazine®(PDZ)] and light (LED), either singly or combined. The treatments were performed for 5 consecutive days. Treatment efficacy was evaluated by assessing the tongues via fungal viable population, clinical evaluation, histopathological and fluorescence microscopy methods immediately after finishing treatments, and 7 days of follow-up. The combination of DNase with PDZ-aPDT reduced the fungal viability in mice tongues immediately after the treatments by around 4.26 and 2.89 log10 for CaS and CaR, respectively (versus animals only inoculated). In the fluorescence microscopy, the polysaccharides produced by C. albicans and fungal cells were less labeled in animals treated with the combination of DNase with PDZ-aPDT, similar to the healthy animals. After 7 days of the treatment, DNase associated with PDZ-aPDT maintained a lower count, but not as pronounced as immediately after the intervention. For both strains, mice treated with the combination of DNase with PDZ-aPDT showed remission of oral lesions and mild inflammatory infiltrate in both periods assessed, while animals treated only with PDZ-aPDT presented partial remission of oral lesions. DNase I enzyme improved the efficacy of photodynamic treatment.

Photodynamic Inactivation of Botrytis cinerea Spores by Curcumin—Effect of Treatment Factors and Characterization of Photo-generated Reactive Oxygen Species

AbstractBotrytiscinerea is the main cause of gray mold in a wide range of fresh produce, which causes huge losses in pre- and/or post-harvest stages and is therefore considered the second major plant pathogen globally. Since the application of synthetic fungicides is not allowed in postharvest conditions, alternative natural approaches are required to reduce the resulting spoilage. The aim of this study was to investigate the efficacy of photodynamic treatment in inactivating B. cinerea spores in vitro, for which the interactive effect of influential treatment parameters on curcumin phototoxicity was studied using an I-optimal design. Results showed that the antifungal activity of the treatment was significantly dependent on solvent, curcumin concentration, and irradiance, except for light dose. A complete photoinactivation of spores was obtained in an aqueous ethanolic environment (optimum condition: 13 μM, 31.75 mW cm−2, 19.05 J cm−2), compared to when curcumin was dissolved in medium-chain-triglyceride (MCT) oil. Furthermore, the photogeneration of superoxide anion and hydroxyl radicals was demonstrated by electron paramagnetic resonance spectroscopy, which indicates the occurrence of a type-I photodynamic reaction. These findings suggest that curcumin-based photosensitization can inhibit/reduce fungal infection, which can be employed in pre/post-harvest stages to reduce the waste caused by spoilage.

Novel Chlorin e6-Curcumin Derivatives as a Potential Photosensitizer: Synthesis, Characterization, and Anticancer Activity.

Novel series of chlorin e6-curcumin derivatives were designed and synthesized. All the synthesized compounds 16, 17, 18, and 19 were tested for their photodynamic treatment (PDT) efficacy against human pancreatic cancer cell lines: AsPC-1, MIA-PaCa-2, and PANC-1. The cellular uptake study was performed in the aforementioned cell lines using fluorescence-activated cell sorting (FACS). 17, among the synthesized compounds with IC50 values of 0.27, 0.42, and 0.21 µM against AsPC-1, MIA PaCa-2, and PANC-1 cell lines, respectively, demonstrated excellent cellular internalization capability and exhibited higher phototoxicity relative to the parent Ce6. The quantitative analyses using Annexin V-PI staining revealed that the 17-PDT-induced apoptosis was dose-dependent. In pancreatic cell lines, 17 reduced the expression of the anti-apoptotic protein, Bcl-2, and increased the pro-apoptotic protein, cytochrome C, which indicates the activation of intrinsic apoptosis, the primary cause of cancer cell death. Structure-activity relationship studies have shown that the incorporation of additional methyl ester moiety and conjugation to the enone moiety of curcumin enhances cellular uptake and PDT efficacy. Moreover, in vivo PDT testing in melanoma mouse models revealed that 17-PDT greatly reduced tumor growth. Therefore, 17 might be an effective photosensitizer for PDT anticancer therapy.

Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: An in vivo study

Background and aimAntimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections. MethodsThe cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer. ResultsAE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald. ConclusionsAE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.

Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms.

Nanocarriers for drug delivery have made great progress in the treatment of cancer, but the dense extracellular collagen of tumors has greatly limited the efficiency of drug delivery. In this study, losartan is used to deplete tumor collagen and improve the delivery efficiency and photodynamic therapeutic efficacy of chlorine 6 (Ce6)-loaded periodic mesoporous organosilica nanoplatform (Ce6-PMO) for breast cancer. After pretreatment with losartan in vivo, the tumor collagen I fraction is significantly reduced by 53% compared to that of mice pretreated with saline. Importantly, the accumulation of the Ce6-PMO nanoplatforms in the tumor is remarkably enhanced via peritumoral and intravenous injection, respectively, after the mice are pretreated with losartan. Further, combination of losartan with the Ce6-PMO nanoplatforms shows the best therapeutic efficacy, and the suppression rate of tumor volume is measured up to 82%. Taken together, this study provides a very promising synergetic strategy to improve the tumor photodynamic treatment efficacy of nanoplatforms.

Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

Effects of photodynamic laser and violet-blue led irradiation on Staphylococcus aureus biofilm and Escherichia coli lipopolysaccharide attached to moderately rough titanium surface: in vitro study.

Effective decontamination of biofilm and bacterial toxins from the surface of dental implants is a yet unresolved issue. This study investigates the in vitro efficacy of photodynamic treatment (PDT) with methylene blue (MB) photoactivated with λ 635nm diode laser and of λ 405nm violet-blue LED phototreatment for the reduction of bacterial biofilm and lipopolysaccharide (LPS) adherent to titanium surface mimicking the bone-implant interface. Staphylococcus aureus biofilm grown on titanium discs with a moderately rough surface was subjected to either PDT (0.1% MB and λ 635nm diode laser) or λ 405nm LED phototreatment for 1 and 5min. Bactericidal effect was evaluated by vital staining and residual colony-forming unit count. Biofilm and titanium surface morphology were analyzed by scanning electron microscopy (SEM). In parallel experiments, discs coated with Escherichia coli LPS were treated as above before seeding with RAW 264.7 macrophages to quantify LPS-driven inflammatory cell activation by measuring the enhanced generation of nitric oxide (NO). Both PDT and LED phototreatment induced a statistically significant (p < 0.05 or higher) reduction of viable bacteria, up to -99 and -98% (5min), respectively. Moreover, besides bactericidal effect, PDT and LED phototreatment also inhibited LPS bioactivity, assayed as nitrite formation, up to -42%, thereby blunting host inflammatory response. Non-invasive phototherapy emerges as an attractive alternative in the treatment of peri-implantitis to reduce bacteria and LPS adherent to titanium implant surface without causing damage of surface microstructure. Its efficacy in the clinical setting remains to be investigated.

Lipid nanoemulsions and liposomes improve photodynamic treatment efficacy and tolerance in CAL-33 tumor bearing nude mice

BackgroundPhotodynamic therapy (PDT) as promising alternative to conventional cancer treatments works by irradiation of a photosensitizer (PS) with light, which creates reactive oxygen species and singlet oxygen (1O2), that damage the tumor. However, a routine use is hindered by the PS’s poor water solubility and extended cutaneous photosensitivity of patients after treatment. In our study we sought to overcome these limitations by encapsulation of the PS m-tetrahydroxyphenylchlorin (mTHPC) into a biocompatible nanoemulsion (Lipidots).ResultsIn CAL-33 tumor bearing nude mice we compared the Lipidots to the existing liposomal mTHPC nanoformulation Foslip and the approved mTHPC formulation Foscan. We established biodistribution profiles via fluorescence measurements in vivo and high performance liquid chromatography (HPLC) analysis. All formulations accumulated in the tumors and we could determine the optimum treatment time point for each substance (8 h for mTHPC, 24 h for Foslip and 72 h for the Lipidots). We used two different light doses (10 and 20 J/cm2) and evaluated immediate PDT effects 48 h after treatment and long term effects 14 days later. We also analyzed tumors by histological analysis and performing reverse transcription real-time PCR with RNA extracts. Concerning tumor destruction Foslip was superior to Lipidots and Foscan while with regard to tolerance and side effects Lipidots were giving the best results.ConclusionsWe could demonstrate in our study that nanoformulations are superior to the free PS mTHPC. The development of a potent nanoformulation is of major importance because the free PS is related to several issues such as poor bioavailability, solubility and increased photosensibility of patients. We could show in this study that Foslip is very potent in destroying the tumors itself. However, because the Lipidots' biocompatibility is outstanding and superior to the liposomes we plan to carry out further investigations and protocol optimization. Both nanoformulations show great potential to revolutionize PDT in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-016-0223-8) contains supplementary material, which is available to authorized users.

Specific cellular accumulation of photofrin-II in EC cells promotes photodynamic treatment efficacy in esophageal cancer

Photodynamic therapy (PDT), which uses a light-sensitive compound and laser irradiation, is a light-based oncological treatment modality. PDT offers an alternative, less invasive treatment for various malignant tumors, such as esophageal cancer (EC), through a photochemical reaction induced by photofrin-II or other oncotropic photosensitizers without severe complications. Previous studies has shown that cancerous tissues accumulated more photosensitizers than paired normal tissues, however, whether it is cellular or vascular mechanisms remains unknown. Herein, in vivo and in vitro examinations were performed to study the mechanisms by which photofrin-II effectively and specifically killed EC cells. In this study, EC tissue of patients treated with photofrin-II, human ESCC cellline SHEEC and parental normal cellline SHEE, primary culture cells of EC tissue were used. The concentration of photofrin-II in cells were evaluated by high-performance liquid chromatography (HPLC). The results exhibited that accumulation of photofrin-II in cancerous cells were significantly higher than that in non-cancerous cells (p<0.05) under certain dose and time period of incubation of photofrin-II. In summary, our study showed that, photofrin-II specifically accumulated in EC cells in vivo and in vitro after controlling for vascular factors, which provided strong evidence that maybe the cellular factor is the main mechanism by which photofrin-II-mediated PDT selectively caused EC cells death.

GJIC Enhances the phototoxicity of photofrin-mediated photodynamic treatment by the mechanisms related with ROS and Calcium pathways.

Despite initially positive responses, recurrences after Photodynamic treatment (PDT) can occur and there is need for improvement in the effectiveness of PDT. Our study uniquely showed that there was a significantly gap junctional intercellular communication (GJIC)-dependent PDT cytotoxicity. The presence of GJIC composed of Connexin 32 increased the PDT phototoxicity in transfected HeLa cells and in the xenograft tumors, and the enhanced phototoxicity of Photofrin-mediated PDT by GJIC was related with ROS and calcium pathways. Our study indicates the possibility that up-regulation or maintenance of gap junction functionality may be used to increase the efficacy of PDT. The phototoxicity effect of Photofrin was substantially greater in Dox-treated cells, which expressed the Cx32 and formed the GJ, than Dox-untreated.

Photophysical properties and photodynamic activity of nanostructured aluminum phthalocyanines

We developed water-soluble supramolecular complexes of aluminium phthalocyanine based on mesoporous silica nanoparticles and polyvinylpirrolidone containing rare photoactive nanoaggregates. Radiative lifetimes, extinction coefficients and energy of electronic transitions of isolated and associated metal phthalocyanine complexes were calculated. Nontoxic concentrations of synthesized nanocomposite photosensibilizers were in vitro determined. In present study we compared photodynamic treatment efficacy using different modifications of aluminium phthalocyanine (Photosens®, AlPc-nSiO2 and AlPc-PVP). Mesenchymal stromal cells were used as a model for photodynamic treatment. Intracellular accumulation of aluminium phthalocyanine based on mesoporous silica nanoparticles AlPc-nSiO2 was the most efficient. Illumination of phthalocyanine-loaded cells led to reactive oxygen species generation and subsequent apoptotic cell death. Silica nanoparticles provided a significant decrease of effective phthalocyanine concentration and enhanced cytotoxicity of photodynamic treatment.

Photodynamic and Nail Penetration Enhancing Effects of Novel Multifunctional Photosensitizers Designed for The Treatment of Onychomycosis

Novel multifunctional photosensitizers (MFPSs), 5,10,15-tris(4-N-methylpyridinium)-20-(4-phenylthio)-[21H,23H]-porphine trichloride (PORTH) and 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE), derived from 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as photosensitizer for photodynamic treatment (PDT) of onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532nm continuous-wave 5mWcm(-2) laser light (±argon/mannitol/NaN3 ). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy. PDT efficacy was tested (pH 5, ±argon/mannitol/NaN3 ) in vitro with Trichophyton mentagrophytus microconida (532nm, 5mWcm(-2) ). A light-dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable. Argon and mannitol increased PORTH and PORTHE photostability; NaN3 had no effect. PDT (0.6Jcm(-2) , 2μm) showed 4.6 log kill for PORTH, 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10μm). Argon increased PORTHE, but decreased PORTH PDT efficacy; NaN3 increased PDT effect of both MFPSs whereas mannitol increased PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low oxygen conditions and thus realistic candidate for onychomycosis PDT.

Photodynamic treatment of oral squamous cell carcinoma in hamster cheek pouch model using chlorin p6-histamine conjugate.

Over-expression of histamine receptors has been reported in several types of malignancies. Earlier we have successfully demonstrated use of chlorin p6-histamine conjugate (Cp6-his) for improving cellular uptake and photo toxicity of Cp6 in oral cancer cell lines. In the present study, after having confirmed that histamine receptors are over-expressed in tumors of hamster cheek pouch, we investigated the efficacy of Cp6-his for photodynamic treatment (PDT) of tumors in this animal model. Cp6-his (3mg/kg body weight) was injected intraperitoneally and its accumulation in tumor, surrounding tissue, normal mucosa and abdominal skin was monitored non-invasively by fluorescence spectroscopy. For PDT, tumors at 4h after Cp6-his administration were exposed to red light (660±25nm, 100J/cm(2)). Tumor damage and regression were assessed by histology and tumor volume measurements, respectively. Expression of histamine H2 receptors in tumor and normal mucosa was assessed by immuno-staining. The accumulation of Cp6-his was higher in tumors as compared to normal mucosa at 4h after its administration. For Cp6 similar preferential accumulation was observed except that in normal mucosa the accumulation of Cp6 was more as compared to Cp6-his. The clearance of Cp6-his from skin was rapid showing ∼80% decrease within 48h from its peak level at 4h after drug injection. PDT led to extensive cellular damage and tumors of size up to ∼1000mm(3) regressed completely one week after PDT. Higher tumor selectivity of Cp6-his and complete regression of bigger tumors after PDT suggest that conjugating Cp6 to histamine is a promising approach to improve PDT efficacy.

Fluorescence detection and depletion of T47D breast cancer cells from human mononuclear cell-enriched blood preparations by photodynamic treatment: Basic in vitro experiments towards the removal of circulating tumor cells

A major obstacle for permanent cancer eradication is the persistence of circulating tumor cells (CTCs) in blood, which often escape radio- or chemotherapy. Currently no efficient strategy to remove CTCs from peripheral blood in order to lower the risk of metastases or tumor recurrence exists. Photodynamic treatment (PDT) using aminolevulinic acid (ALA) induced protoporphyrin IX (PPIX) as photosensitizer offers an innovative approach to overcome this problem. This study aims at providing basic evidence towards fluorescence detection and photodynamic depletion of scattered cancer cells from blood preparations. The breast cancer cell line T47D, endothelial GP8 cells, red blood cells (RBCs) and peripheral blood mononuclear cells (MNCs) have been tested for ALA-induced formation kinetics of PPIX by flow cytometry and microplate fluorescence analysis. The influence of the presence of RBCs on the PPIX-accumulation in cancer cells was evaluated by flow cytometry; the efficacy of PDT on cancer cells and MNCs has been tested by resazurin assay. Mixtures of T47D and GP8 cells and MNCs spiked with cancer cells were tested to determine the limit of fluorescence detection by flow cytometry and antibody co-staining. T47D cells accumulated significantly higher PPIX-amounts after ALA-incubation than any other cell type tested. The presence of RBCs had no impact on PPIX-formation in T47D cells. Experiments towards the fluorescence detection of cancer cells in blood revealed that the sensitivity of this method is yet limited. Viability testing after PDT showed that cancer cells where almost completely eradicated after illumination whereas MNCs were almost spared. We clearly demonstrate in vitro tumor cell selectivity of PPIX-accumulation over endothelial cells, MNCs and RBCs. Breast cancer cells are efficiently killed by PDT with minor depletion of MNCs. Our findings provide a basis for the PDT of blood samples for a future depletion of CTCs.

Synthetic approaches for the conjugation of porphyrins and related macrocycles to peptides and proteins

The association of photosensitisers to peptides and proteins is a recognised and successful method for enhancing the selectivity and efficacy of photodynamic treatment. The covalent attachment of porphyrins and related macrocycles to peptides and proteins can generate new phototoxic species that allow the concentration of the oxidative damage to the target area, thanks to their enhanced cellular uptake, favourable sub-cellular distribution, and ability to target receptors or enzymes over-expressed by a given tissue or cell. The need to exert control over the regioselectivity of the conjugation led to the exploration of a variety of chemistries; in some cases based on bioorthogonal ligations, in others exploring the reactivity of naturally occurring functional groups. In this review we place a major emphasis on the synthetic strategies adopted to generate such conjugates. All such strategies will be surveyed, together with the methods used to introduce or unmask the appropriate reactive functionalities both on the peptide moiety and the photosensitiser.

Tumor selectivity and photodynamic treatment efficacy of chlorin p6-histamine conjugate in Hamster cheek pouch tumor model

Tumor selectivity and photodynamic treatment efficacy of chlorin p6-histamine conjugate in Hamster cheek pouch tumor model

In vitro and in vivo targeted delivery of photosensitizers to the tumor cells for enhanced photodynamic effects

Efficacy of photodynamic therapy can be enhanced by improving uptake, localization, and sub-cellular localization of sensitizers at the sensitive targets. Uptake, localization, and photodynamic effects of hematoporphyrin derivative (HpD, Photosan-3; PS-3) and disulfonated aluminum phthalocyanine (AlPcS₂) were studied either encapsulated in liposomes or conjugated to a monoclonal antibody to carcinoembryonic antigen (anti-CEA) in a brain glioma cell line, BMG-1. Although the total uptake with encapsulated or conjugated sensitizers was less than the free sensitizers, photodynamic efficiency was higher due to the localization of the sensitizer at the sensitive targets. Biodistribution of intravenously administered technetium (⁹⁹m Tc)-labeled PS-3 analyzed by gamma camera imaging showed maximum accumulation in the liver followed by tumor. Tumor/muscle (T/N) ratio of free PS-3 was higher compared to encapsulated or conjugated PS-3 but the accumulation of PS-3 significantly reduced in brain and cutaneous tissue following modulated delivery. Pharmacokinetics suggested faster accumulation of encapsulated and conjugated PS-3 in the tumor. Localization of sensitizers at sensitive targets and reduced accumulation in normal tissues with liposome encapsulation and antibody conjugation suggest that these two delivery systems can potentially enhance the efficacy of photodynamic treatment.