Positron emission tomography guided synergistic treatment of melanoma using multifunctional zirconium-hematoporphyrin nanosonosensitizers.

Sonodynamic therapy (SDT) has emerged as a useful approach for tumor treatment. However, its widespread application is impeded by poor pharmacokinetics of existing sonosensitizers. Here we developed a metal-organic nanoplatform, wherein a small-molecule sonosensitizer (hematoporphyrin monomethyl ether, HMME) was ingeniously coordinated with zirconium, resulting in a multifunctional nanosonosensitizer termed Zr-HMME. Through post-synthetic modifications involving PEGylation and tumor-targeting peptide (F3) linkage, a nanoplatform capable of homing on melanoma was produced, which could elicit robust immune responses to suppress tumor lung metastasis in the host organism. Importantly, after seamless incorporation of positron-emitting 89Zr into this nanosonosensitizer, positron emission tomography (PET) could be used to monitor its in vivo pharmacokinetics. PET imaging studies revealed that this nanoplatform exhibited potent tumor accumulation and strong in vivo stability. Using intrinsic fluorescence from HMME, a dual-modal diagnostic capability (fluorescence and PET) was confirmed for this nanosonosensitizer. In addition, the mechanisms of how this nanoplatform interacted with immune system were also investigated. The collective data proved that the coordination structure between small-molecule drug cargos and metals may enhance the functions of each other while mitigating their weaknesses. This straightforward approach can expand the potential applications of suitable drug molecules.

Efficacy of hemoporfin photodynamic therapy for pulsed dye laser-resistant facial port-wine stains in 107 children: A retrospective study.

BACKGROUND: Port-wine stains occur in 0.3-0.5% newborns, mainly on the face and neck. Pulsed dye laser is recognized as the gold standard treatment; nevertheless, it is associated with a low cure rate and a high recurrence rate. AIMS: This study aims to evaluate the efficacy of hemoporfin photodynamic therapy for pulsed dye laser-resistant port-wine stains in children. METHODS: We studied 107 children who received hemoporfin photodynamic therapy for port-wine stains on the face and neck that were resistant to pulsed dye laser. After intravenous injection of 5 mg/kg hemoporfin, the local lesion was irradiated with 532 nm LED green light for 20 min with a power density of 80-100 mW/cm2. A total of 65 patients were given a second treatment after eight weeks. The efficacy and therapeutic responses were recorded at four days and eight weeks after each treatment. RESULTS: The efficacy was positively correlated with the number of treatments received; two treatment sessions yielded significantly better results compared to a single treatment with a response rate of 96.9%, a significant response rate of 50.8% and a cure rate of 21.5%, respectively (P < 0.001). After two treatment sessions, the efficacy was negatively correlated with age (P = 0.04). The efficacy for port-wine stains located on the lateral part was better than that of the central face (P = 0.04). The efficacy for the pink type was better than that for the red and purple types (P = 0.03). No allergic or systematic adverse reactions were reported. LIMITATIONS: No objective measurement data were available. CONCLUSION: Hemoporfin photodynamic therapy is effective and safe for pulsed dye laser-resistant facial port-wine stains in children.

Dual Size/Charge-Switchable Nanocatalytic Medicine for Deep Tumor Therapy.

Elevating intratumoral levels of highly toxic reactive oxygen species (ROS) by nanocatalytic medicine for tumor-specific therapy without using conventional toxic chemodrugs is recently of considerable interest, which, however, still suffers from less satisfactory therapeutic efficacy due to the relatively poor accumulation at the tumor site and largely blocked intratumoral infiltration of nanomedicines. Herein, an ultrasound (US)-triggered dual size/charge-switchable nanocatalytic medicine, designated as Cu-LDH/HMME@Lips, is constructed for deep solid tumor therapy via catalytic ROS generations. The negatively charged liposome outer-layer of the nanomedicine enables much-prolonged blood circulation for significantly enhanced tumoral accumulation, while the positively charged Fenton-like catalyst Cu-LDH released from the liposome under the US stimulation demonstrates much enhanced intratumoral penetration via transcytosis. In the meantime, the co-released sonosensitizer hematoporphyrin monomethyl ether (HMME) catalyze the singlet oxygen (1O2) generation upon the US irradiation, and deep-tumoral infiltrated Cu-LDH catalyzes the H2O2 decomposition to produce highly toxic hydroxyl radical (·OH) specifically within the mildly acidic tumor microenvironment (TME). The efficient intratumoral accumulation and penetration via the dual size/charge switching mechanism, and the ROS generations by both sonosensitization and Fenton-like reactions, ensures the high therapeutic efficacy for the deep tumor therapy by the nanocatalytic medicine.

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance.

This study aims at exploring the clinical efficacy and sonographic changes of photodynamic therapy (PDT) using Hematoporphyrin Monomethyl Ether (HMME) for the treatment of port-wine stains (PWS). Forty-five patients with PWS were recruited between March 2017 and June 2018 from the Department of Dermatology of The Third Affiliated Hospital of Soochow University. Five cases were of the pink type, thirty-nine cases were of the purple-red type, and one case was of the thickened type. All patients received three treatment sessions of PDT. After covering normal skin outside the treated area, patients received an intravenous injection of 5 mg/kg HMME within 20 minutes. The affected areas were exposed to a 532 nm LED light and were kept vertically at a distance of 10 cm. The irradiation energy density was set between 80 and 110 J/cm2 in 15-minute sessions. Intermittent power density adjustment was performed at a rate of 5 mW/cm2, and the treatment was withheld when the endpoint reaction appeared. Three follow-ups were performed before and after treatment, respectively, and the efficacy, thickness, and density of skin before and after treatment were evaluated with high-frequency ultrasound. The overall efficacy rate was 97.78% in forty-five cases after treatment for three sessions. Efficacy was related to age (P = 0.029) and lesion severity (P < 0.001). There were significant differences in the efficacy between the groups of <18 years old, 18-29 years old, and >29 years old (P = 0.029). A marked decrease in the numbers of distorted enlarged blood vessels per unit of the lesion was observed under high-frequency ultrasound. There were significant differences in skin thickness and skin density before and after treatment (F = 14.528, 5.428, P < 0.001). The swelling was reported to varying degrees in the treated areas in 23 patients with cheek lesion and in 6 frontal lesions. Hyperpigmentation after inflammation was observed in four patients that faded spontaneously after two months. In conclusion, photodynamic therapy for the treatment of PWS using HMME is effective and safe with few adverse reactions. Moreover, monitoring the changes in skin thickness and density of lesion tissue using high-frequency ultrasound can objectively evaluate the clinical efficacy of HMME photodynamic therapy and provide the basis for the formulation of individualized photodynamic therapy.

Preparation, characterization, and sonodynamic antitumor effect of the folate receptor targeted FA-EN-ß-CD containing hematoporphyrin in vitro.

To improve water solubility, reduce phototoxicity and increase the tumor-targeting ability of hematoporphyrin (Hp) as a sonosensitizer for sonodynamic therapy under ultrasonic conditions, a novel folate receptor (FR)-targeted, folate-conjugated ethylenediamine-ß-cyclodextrin (FA-EN-ß-CD) containing Hp (FA-EN-ß-CD-Hp) was constructed. ß-Cyclodextrin containing Hp (ß-CD-Hp) was also established as a nontargeted control. The inclusion efficiencies of Hp in FA-EN-ß-CD-Hp and ß-CD-Hp were determined to be 90.4 ± 2.7% (wt/wt) and 92.5 ± 3.4% (wt/wt), respectively. Growth inhibition rates in HepG-2 cells in vitro were assessed upon ultrasound exposure. The results indicated that the growth inhibition rates of FA-EN-ß-CD-Hp, ß-CD-Hp, and F-Hp (Hp: 150 µg/ml) reached 96.4 ± 3.6%, 53.4 ± 3.4%, and 48.2 ± 2.8%, respectively. These results indicated that FA-EN-ß-CD-Hp is a promising drug delivery system in the field of sonodynamic cancer therapy.

Retrospective study of photodynamic therapy for pulsed dye laser-resistant port-wine stains.

Pulsed dye laser-resistant port-wine stains present a therapeutic challenge. The aim of this study was to evaluate the efficacy and safety of photodynamic therapy for treating these lesions. A total of 67 patients with pulsed dye laser-resistant cervicofacial port-wine stains were retrospectively assessed after undergoing photodynamic therapy mediated with a combination of hemoporfin and 532-nm light. For objective evaluation of photodynamic therapy efficacy, first, the colorimetric changes in the port-wine stain lesions were evaluated according to the L*a*b* color coordinate system, then the values of color changes (ΔE) and blanching rate were calculated. For subjective evaluation of improvement, photographs taken before and after photodynamic therapy were evaluated by three independent assessors blindly. Patient satisfaction was also used as a factor in the subjective evaluation. Adverse events were recorded after treatment. The median ΔE decreased significantly from the pretreatment value of 13.42 to 9.90 at the 2-month follow up (P < 0.001). The median blanching rate of port-wine stains was 28.04% after an average of 1.21 sessions of photodynamic therapy. Based on the overall visual assessment, 46.2% patients showed excellent or good levels of improvement (>50% color blanching). Adverse events were minimal, transient and self-limiting. In conclusion, photodynamic therapy serves as an alternative means to treat pulsed dye laser-resistant port-wine stains.

Efficacy and related factors analysis in HMME-PDT in the treatment of port wine stains.

OBJECTIVE: To observe the efficiency and safety of hematoporphyrin mono-methylether photodynamic therapy (HMME-PDT) in treating port-wine stains (PWS) with Chinese patients, and to evaluate the advantage of photograph,VISIA Complexion Analysis System, and dermoscopy in efficacy evaluation.Analyzing changes of pain during treatment and related adverse reactions. METHOD: 62 patients were treated in our department during2017-2019 with HMME-PDT, among which, 20 cases were pink type, 32 cases were purple type and remain 11 cases were nodular thickening type. Initially, all patients received an intravenous injection of 5 mg/kg HMME, and then the lesion areas of the patients were exposed to 532 nm LED green light after 10 min. The irradiation power density was range between 80-100 mW/cm2. By utilization of photograph,VISIA system, and dermoscopy to evaluate the clearance after treatments, and then informing the patients to value the pain level during the treatment via visual analogue scale(VAS), and recording the adverse reactions. RESULT: After 2 times treatments, 11 of the 62 cases were cured (17.74 %), 17 cases showed a good efficacy (27.42 %), 20 cases indicated alleviation (32.26 %), while 14 cases displayed no efficacy (22.58 %).By observation, The VISIA system combined with image analysis software is an excellent technique in assessing efficacy. Dermoscopy helps to classify PWS types.It showed that the pain level each patient could endure was distinct, and it's remarkable that when receiving consecutive 12.09 ± 3.74 min of treatment, most of patients have showed severe pain.Patients with severe pain except young children who couldn't value the pain, had better efficacy.The side effects after treatment mainly displayed with edema, crust, hyperpigmentation. No recurrence within 2 years. CONCLUSION: It shows that after treating with HMME-PDTt efficacy is remarkable, with advantage of safety and fewer side effects. HMME_PDT should undergo further research and promotion. VISIA system combined with image analysis software and dermoscopy are excellent techniques for evaluating efficacy.

Multi-path tumor inhibition via the interactive effects between tumor microenvironment and an oxygen self-supplying delivery system for a photosensitizer.

The tumor microenvironment (TME) affects not only tumor growth and metastasis, but also therapy efficacy. In the present study, an oxygen self-supplying delivery system for a photosensitizer (O2-PDS), with an oxygen source of calcium peroxide (CPO), has been designed to induce multi-path tumor apoptosis through interactive effects with the TME. In anti-tumor experiments, the CPO decomposition and O2 released from the O2-PDS are site-activated and accelerated by high interstitial pressure and low pH level of the TME. The CPO decomposition products of O2 and Ca2+ lead to direct tumor apoptosis by irradiation generated singlet oxygen and mitochondrial calcium overload. The decomposition products of OH- and O2 relieves the acid and hypoxic state of TME, inducing a decrease in tumor proliferation and metastasis. This multi-path tumor apoptosis leads to a positive therapeutic effect on an animal tumor model and nontoxicity in normal tissue.

Development and characteristics of novel sonosensitive liposomes for vincristine bitartrate.

The aim of drug delivery is to increase therapeutic efficacy. Externally triggered drug delivery systems enable site-specific and time-controlled drug release. To achieve this goal, our strategy was based on ultrasound-triggered release of an anticancer agent from sonosensitive liposomes (SL). To realize the ultrasound-triggered drug release, a lipophilic sonosensitizer, hematoporphyrin monomethyl ether (HMME) was incorporated into the lipid bilayer of liposomes. Once irradiated by the ultrasound in tumor tissues, the sonodynamic effect generated by HMME could lead to an efficient disruption of the lipid bilayer in the SL. After encapsulating vincristine bitartrate (VIN) as the model drug, the ultrasound-triggered lipid bilayer breakdown can trigger the instant release of VIN, enabling ultrasound-controlled chemotherapy with great specificity. In the in vitro and in vivo studies, by integrating tumor-specific targeting and stimuli-responsive controlled release into one system, VIN-loaded SL showed excellent antitumor efficacy. The SL could potentially produce viable clinical strategies for improved targeting efficiency of VIN for the treatment of related cancer. More importantly, this report provides an example of controlled release by means of a novel class of ultrasound triggering system.

Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice.

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy.

Alteration of Surface Glycoproteins After Photodynamic Therapy.

BACKGROUND: Cell membranes have been identified as an important intracellular cancer treatment target, since the glycoconjugates present on the cell surface are involved in numerous cell functions. Photodynamic therapy (PDT) is a therapeutic modality employed in the treatment of tumors that uses visible light to activate a photosensitizer. OBJECTIVE: This study analyzed the expression of surface carbohydrates after PDT with two different photosensitizers, 5-aminolevulinic acid (ALA) and Photosan-3. METHODS: Mice were injected subcutaneously with 2 × 105 B16 cells. After 7-10 days, the presence of a tumor with a diameter of 3.6 mm was observed. Photosan-3® and 5-aminolevulinic acid-ALA were used in the PDT treatment. Control animals (not submitted to either laser treatment or photosensitizer injection) and treated animals were euthanized 15 days post-treatment. The tumors were irradiated with a red diode laser, λ = 655 nm, energy density of 10 J.cm-2, and power density of 45 mW.cm-2. After 2 weeks of treatment with PDT, the mice were euthanized, the tumors were collected, and the cell surfaces were labeled with lectins concanavalin A (ConA) and wheat germ agglutinin (WGA). RESULTS: Fluorescence microscopy analysis of the cell surfaces with lectins ConA and WGA showed the presence of α-mannose and α-glucose. CONCLUSIONS: The combined effects of either Photosan-3 or ALA and red laser light on melanoma suggest an inhibitory glycosylation action from PDT on the surface of B16-F10 cells.

Photodynamic therapy-mediated remote control of chemotherapy toward synergistic anticancer treatment.

Stimuli-responsive nanomedicine (NM) with an on-demand drug release property has demonstrated promising utility toward cancer therapy. However, sensitivity and cancer selectivity still remain critical challenges for intelligent NM, which will compromise its therapeutic efficacy and lead to undesired toxicity to normal tissues. Herein, we report a convenient and universal approach to spatiotemporally control the chemodrug release via the photodynamic therapy (PDT)-mediated alteration of the tumor microenvironment. An arylboronic ester (BE)-modified amphiphilic copolymer (mPEG-PBAM) was designed to form micelles and encapsulate doxorubicin (Dox) and hematoporphyrin (Hp). The Dox/Hp co-encapsulated micelles (PB-DH) were stable under normal physiological environment with a uniform size distribution (∼100 nm). In contrast, under tumor-specific light irradiation, extensive reactive oxygen species (ROS) will be generated from Hp in the tumor sites, thus quickly dissociating the micelles and selectively releasing the chemodrug Dox as a consequence of the ROS-mediated cleavage of the hydrophobic BE moieties on the polymers. As such, synergistic anti-cancer efficacy was achieved between the Dox-mediated chemotherapy and the Hp-mediated PDT. This study therefore provides a useful approach to realize the precise and selective control over chemodrug delivery, and it renders promising utilities for the programmable combination of PDT and chemotherapy.

A clinical study of HMME-PDT therapy in Chinese pediatric patients with port-wine stain.

OBJECTIVE: To report our observations from a trial of the effectiveness and safety of hematoporphyrin monomethyl ether photodynamic therapy (HMME-PDT) in treating Chinese Pediatric patients port-wine stains (PWS). METHOD: From October 2017 to December 2017, the study recruited 82 patients of PWS with negative HMME skin test results. The patients received an intravenous injection of 5 mg/kg HMME and the affected areas were exposed to 532 nm LED green light, with the irradiation power density between 80-85 mW/cm2. Each light spot was irradiated for 20-25 min. After two treatments, the clinical efficacy and posttreatment reactions at each treated area were observed. RESULT: The patient age between 1 and 14 years old. 24 of the 82 cases were cured (29.27%) after two HMME-PDT treatment, 34 cases indicates a good efficacy (41.46%), 16 cases showed alleviation (19.51%), while 8 cases displayed no efficacy (9.76%). Pain was observed during treatment, and post-treatment edema was observed at the treated areas. No other obvious systematic adverse reaction were reported. CONCLUSION: HMME-PDT is an effective and safe treatment for pediatric patients with PWS.

A dose-finding study for hemoporfin in photodynamic therapy for port-wine stain: A multicenter randomized double-blind phase IIb trial.

BACKGROUND/PURPOSE: Previous studies have shown that hemoporfin-mediated photodynamic therapy (PDT) was a treatment for port-wine stain (PWS). Our current study aimed to identify optimal hemoporfin dose. METHODS: A prospective, multicenter, double-blind, randomized clinical trial was conducted. Patients were assigned into low- or high-dose hemoporfin (2.5 mg/kg and 5 mg/kg intravenously, respectively), or control (placebo) group, at a rate of 2:2:1. Treatment efficacy was evaluated at week 8. Then, patients in control group were randomly assigned into either high- or low-dose hemoporfin group. Treatment reactions and adverse events were analyzed at week 16. RESULTS: A total of 100 patients (40, 40, 20 in low-, high-dose hemoporfin, and control group, respectively) were enrolled. Compared to low dose (40%) and control group (15%), a higher proportion of patients in high-dose group (75%) had achieved skin lesion improvements. Treatment satisfactions were graded highest in high-dose group. Compared to low-dose group (14.3%), high-dose group (46.0%) had more frequent skin hyperpigmentation, which disappeared 3-6 months after treatment. Other treatment reactions and adverse events were comparable between two groups. CONCLUSIONS: Photodynamic therapy with 5 mg/kg hemoporfin could be an effective and safe treatment for PWS.

Combined Phycocyanin and Hematoporphyrin Monomethyl Ether for Breast Cancer Treatment via Photosensitizers Modified Fe3O4 Nanoparticles Inhibiting the Proliferation and Migration of MCF-7 Cells.

Photodynamic therapy (PDT), combining the laser and photosensitizers to kill tumor cells, has the potential to address many current medical requirements. In this study, magnetic Fe3O4 nanoparticles were first employed as cores and modified with oleic acid (OA) and 3-triethoxysilyl-1-propanamine. Then, the photosensitizers phycocyanin (PC) and hematoporphyrin monomethyl ether (HMME), which might be able to stimulate the cell release of reactive oxygen species after the irradiation of a near-infrared (NIR) laser, were grafted on the surface of such nanoparticles. Our results revealed the high-efficiency inhibition of breast cancer MCF-7 cells growing upon near-infrared irradiation both in vitro and in vivo. Furthermore, it was the synergy between the natural photosensitizers PC and the synthetic photosensitizers HMME that deeply influenced such inhibition compared to the groups that used either of these medicines alone. To utilize the combination of different photosensitive agents, our study thus provides a new strategy for breast cancer treatment.

The association between treatment reactions and treatment efficiency of Hemoporfin-photodynamic therapy on port wine stains: A prospective double blind randomized controlled trial.

BACKGROUND: Research has focused on treatment efficiency and/or treatment reactions of photodynamic therapy (PDT) on port-wine stain (PWS). But few studies reported the association between them. Hence, here we investigated the association between the treatment efficiency and treatment reactions after Hemoporfin (HMME) mediated photodynamic therapy (PDT) on PWS through a prospective study. METHODS: Patients (n=50) with PWS were randomly assigned to the HMME group or the placebo group. Three quit after the first treatment, and forty-seven received two sessions of treatment at an 8-week interval. They were given the treatment at day 1 and evaluations were performed at day 1, day 4 and week 8 in each session. HMME group was treated with HMME while the placebo group was given normal saline instead in the first session, double-blindly. While in the second session, both groups received HMME-PDT treatment. RESULTS: After a single treatment, swelling was more severe in younger patients (p<0.05) and the lesion far from centro-facial showed more severe pruritus and scab. Compared with a single treatment, burning sensation had a higher occurrence rate, while burning sensation and scab were less severe in the second treatment. Importantly, severity of scab and pain (5min after irradiation) were found possibly correlated with the treatment efficiency. CONCLUSION: HMME-PDT on PWS induces several treatment reactions, including pruritus, burning sensation, pain, swelling, blisters and scab. Two sessions of treatments do not have any accumulation effects on treatment reactions. And there might be a positive correlation between treatment efficiency and the severity of scab or pain (at early stage of the therapy), which might help in regulating treatment modalities.

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors.

We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3-6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer.

Sonodynamic effect of hematoporphyrin monomethyl ether on ligature-induced periodontitis in rats.

OBJECTIVES: The aim of this study was to perform a histological evaluation of sonodynamic therapy (SDT) of hematoporphyrin monomethyl ether (HMME) on artificially induced periodontal disease in rats. METHODS: Submerging ligatures were placed at the subgingival region of the first maxillary molar in rats. Eighty rats were randomly assigned into four groups: group 1 received no treatment; group 2 was subjected to 50 µg/mL HMME alone; group 3 was treated with low-intensity ultrasound alone (1 W/cm(2)); and group 4 was treated with 50 µg/mL HMME plus ultrasound irradiation (1 MHz, 30 minutes). Ten rats in each group were euthanized at 7 and 15 days, and periodontal tissue samples were taken for histological examination. RESULTS: The animals treated by SDT showed less bone loss (P<0.05) at all experimental periods than the other three groups. No significant differences were found between the control and HMME groups (P>0.05). CONCLUSION: Our results suggest that HMME-mediated SDT can effectively alleviate the periodontal tissue destruction in artificially induced periodontitis in rats. Hence, SDT may have good clinic potential as a noninvasive treatment of periodontal diseases.

Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model.

BACKGROUND: For glioma, temozolomide (TMZ) is a commonly used chemotherapy drug and photodynamic therapy (PDT) is an important adjuvant therapy. The aim of this study was to evaluate the effect of their combination for the treatment of glioma. METHODS: A rat C6 glioma model using male Wistar rats (n=180) weighing 280-300 g was established. Glioma-bearing rats (n=100) were treated with mock, hematoporphyrin monomethyl ether (HMME), laser or PDT. The expression of P-glycoprotein (P-gp) in endothelial cells of the blood-tumor-barrier and in glioma tissues was detected using immunohistochemistry and western blot, respectively. Glioma-bearing rats (n=40) were treated with normal saline, TMZ (60 mg/m(2) for five consecutive days), PDT (630 nm for 10 min) or a combination of TMZ and PDT. TMZ concentration in glioma tissues was detected using liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) and cell death was observed using transmission microscopy. Concurrently, another batch of 40 glioma-bearing rats was subjected to the same treatment, and the survival of these rats was estimated using Kaplan-Meier analysis. RESULTS: PDT significantly decreased the expression of P-gp in endothelial cells comprising the blood-tumor-barrier and in glioma tissues. The combination of TMZ with PDT significantly increased TMZ concentration in glioma tissues, enhanced glioma cell apoptosis and prolonged the median survival of glioma-bearing rats. CONCLUSION: The combination of PDT with TMZ shows synergistic effect in rat C6 glioma model, indicating its potential clinical use in glioma treatment.