Hematoporphyrin Research Articles

A near-infrared bacteriochlorin nanomedicine for enhanced photodynamic therapy

Photodynamic therapy (PDT) is a greatly promising treatment for cancers due to non-invasiveness and low biotoxicity, but its efficacy is limited by poor water solubility, low selectivity, and short therapeutic wavelength of photosensitizers (PSs). Herein, we construct a near-infrared (NIR) nanomedicine (PEO-PDLA@FBC) by co-assembly of tetrafluorophenyl bacteriochlorin (FBC) with an amphiphilic block copolymer (PEO-b-PDLA). The hydrophobic FBC PS can realize the long blood circulation time by the formation of nano-assemblies, which is conducive to the efficient accumulation of the nanomedicine in tumor. Meanwhile, PEO-PDLA@FBC achieves deeper tissue penetration and higher singlet oxygen generation capability than the control (PEO-PDLA@HP) formed by clinically approved PS hematoporphyrin (HP). Based on the results of in vitro and in vivo experiments, PEO-PDLA@FBC demonstrates superior phototoxicity and anti-tumor efficacy, respectively. Moreover, PEO-PDLA@FBC has almost no side effects and toxicity to normal tissues. Therefore, PEO-PDLA@FBC would be a promising nanomedicine for the clinical PDT.

Bacteria-triggered photodynamic nano-system based on hematoporphyrin-modified chitosan for sustainable plant disease control

Faced with increasingly serious drug resistance and environmental pollution, there is an urgent necessity to develop green and efficient pesticides with new mechanisms of action. A novel antibacterial nano-system for plant protection based on photodynamic action was prepared by grafting hematoporphyrin (HP) onto modified chitosan through ester bonding. The self-quenching effect caused by aggregation of grafted HP could effectively inhibit its photodegradation, thus enhancing its photostability. The breakage of ester bonds induced by enzyme stimulation at the sites of bacterial infection could trigger HP release exerting an efficient photodynamic effect. The antibacterial experiments showed that the nanoparticles (NPs) have good photodynamic antibacterial activity, and the inhibition rate was as high as 96 % after 60 min of light exposure. Adhesion and safety studies have shown that the NPs are well retained on plant foliage without causing damage to the crop. Thus, NPs have great potential in sustainable plant disease management.

An In-Vivo Study of Sonodynamic Therapy with Encapsulated Hematoporphyrin

Purpose: According to the side effects of invasive cancer treatments, Sonodynamic Therapy (SDT) as a noninvasive method for breast adenocarcinoma was considered. Sonosensitizer agents’ encapsulation can improve the accumulation of these drugs in the tumor tissue and reduce treatment side effects. Hence, mice breast adenocarcinoma SDT with Hematoporphyrin (HP) and HP-encapsulated Mesoporous Silica Nanoparticles (HP-MSNs) was carried out.
 Materials and Methods: 96 female breast adenocarcinoma grafted Balb/C mice were randomly divided into 16 groups (n = 6): control, sham, HP, HP-MSN, Ultrasound (US), SDT+HP, and SDT+HP-MSN groups. Sonosensitizer agents were injected intraperitoneally (2.5 or 5 mg/kg, 0.2 ml) 24h before an US radiation (1MHz, 1 or 2 W/cm2, 60 sec). The tumor growth parameters were evaluated 30 days after SDT.
 Results: The inhibition ratio was enhanced by 23, 18, 18, and 16% relative to the control group in HP-MSN (5 mg/kg), HP-MSN (2.5 mg/kg) HP (5 mg/kg) and US (2 W/cm2) groups, respectively, at 18 days after the injection time; whereas, the analysis of findings revealed an antitumor effect in SDT with HP-MSN groups. The Tumor Growth Inhibition (TGI) percentages were 45, 42, and 42% for the SDT (2 W/cm2) + HP-MSN (5 mg/kg), SDT (1 W/cm2) + HP-MSN (5 mg/kg), and SDT (2 W/cm2) + HP (2.5 mg/kg) groups, respectively, on the 18th day post-injection, and T2 and T5 times were higher than that of control and sham groups (P<0.05). The estimated 44-day survival time in the Kaplan-Meier test was 95% in the SDT (2 W/ cm2) + HP-MSN (5 mg/kg) treated group, which had moderately differentiated cells in tumor grading.
 Conclusion: Based on the findings, SDT with HP-encapsulated MSNs (5 mg/kg) has an antitumor effect on breast adenocarcinoma.

A pectin-based photoactivated bactericide nanosystem for achieving an improved utilization rate, photostability and targeted delivery of hematoporphyrin.

Photoactivated pesticides have many advantages, such as high activity, low toxicity, and no drug resistance. However, poor photostability and a low utilization rate limit their practical application. Herein, the photosensitizer hematoporphyrin (HP) was used as a photoactivated pesticide, covalently linked with pectin (PEC) via ester bonds, to prepare an amphiphilic polymer pro-bactericide, and subsequently self-assembled in aqueous solutions to obtain an esterase-triggered nanobactericide delivery system. The fluorescence quenching effect due to the aggregation of HP in nanoparticles (NPs) enabled the inhibition of photodegradation of HP in this system. Esterase stimulation could trigger HP release and increase its photodynamic activity. Antibacterial assays have shown that the NPs had potent antibacterial capacity, almost completely inactivating bacteria after 60 min of exposure to light. The NPs had good adherence to the leaves. Safety assessment indicated that the NPs have no obvious toxic effects on plants. Antibacterial studies on plants have shown that the NPs have excellent antibacterial effects on infected plants. These results provide a new strategy for obtaining a photoactivated bactericide nanosystem with a high utilization rate and good photostability and targeting ability.

Docetaxel prodrug and hematoporphyrin co-assembled nanoparticles for anti-tumor combination of chemotherapy and photodynamic therapy

To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, in vitro anti-tumor activity, pharmacokinetic behavior in rats, in vivo distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (H2O2). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. In vivo pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.

Hematoporphyrin Is a Promising Sensitizer for Dual-Frequency Sono-photodynamic Therapy in Mice Breast Cancer

Background: The combination of sonodynamic and photodynamic therapy (SPDT) may be a new hopeful non-invasive method for cancer treatment, which incorporates a combination of low-intensity ultrasound, laser radiation, and a sensitizer agent. Objectives: This study aimed at evaluating the effects of hematoporphyrin (HP)-mediated SPDT (dual-frequency ultrasound and laser radiation) in the management of mice breast adenocarcinoma. Methods: One hundred and thirty-two female mice with implanted tumors were divided into 22 groups, including sham, laser, 4 groups of dual-frequency ultrasound/laser radiation, 8 groups of HP-mediated SPDT (2.5 and 5 mg/kg), and 8 groups of HP encapsulated in mesoporous silica nanoparticles (HP-MSNs)-mediated SPDT. The sensitizer was administered by intraperitoneal injection and after a 24-hour delay, tumor grafted mice were treated with a combination of dual-frequency ultrasound and laser light. The tumor growth factors were used to assess the treatment outcome. Results: The results indicated that HP or HP-MSNs-mediated SPDT had a delaying tumor growth effect. In the groups treated with dual-frequency ultrasound and laser radiation, the maximum tumor growth inhibition (TGI) ratio was 47.5%, while the maximum TGI ratio in the SPDT groups was 61.6%. The time of T2 and T5 in the case of HP-MSNs-mediated SPDT groups was increased compared with sham and that of HP-mediated SPDT groups (P < 0.05). The inhibition ratio on tumor growth increased in all SPDT groups at 12 days after the treatment. Analysis of experimental data demonstrates that this increase was not declined and persisted over 30 days of treatment. The results indicated that SPDT is effective in relative tumor volume when compared with the sham group (339.1 ± 161 and 1510.8 ± 160, respectively). HP or HP-MSNs-mediated SPDT groups had Grade I (low), while others had Grade III (high) malignancy in the histological study of mice breast adenocarcinoma. Conclusions: The results revealed that when sensitized by dual-frequency SPDT, hematoporphyrin (with and without MSNs), has a promising effect at delaying tumor growth on mice breast cancer. Therefore, it can be appreciated that careful selection of the sensitizer with SPDT will play an eminent role in the success of cancer therapies.

Hydroxy-Porphyrin as an Effective, Endogenous Molecular Clamp during Early Stages of Amyloid Fibrillization.

Amyloid fibril formation of proteins is of great concern in neurodegenerative disease and can be detrimental to the storage and stability of biologics. Recent evidence suggests that insulin fibril formation reduces the efficacy of type II diabetes management and may lead to several complications. To develop anti-amyloidogenic compounds of endogenous origin, we have utilized the hydrogen bond anchoring, π stacking ability of porphyrin, and investigated its role on the inhibition of insulin amyloid formation. We report that hydroxylation and metal removal from the heme moiety yields an excellent inhibitor of insulin fibril formation. Thioflavin T, tyrosine fluorescence, Circular Dichorism (CD) spectroscopy, Field emission scanning electron microscopy (FESEM) and molecular dynamics (MD) simulation studies suggest that hematoporphyrin (HP) having hydrogen bonding ability on both sides is a superior inhibitor compared to hemin and protoporphyrin (PP). Experiments with hen egg white lysozyme (HEWL) amyloid fibril formation also validated the efficacy of endogenous porphyrin based small molecules. Our results will help to decipher a general therapeutic strategy to counter amyloidogenesis.

An intelligent hypoxia-relieving chitosan-based nanoplatform for enhanced targeted chemo-sonodynamic combination therapy on lung cancer

The clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs)-based targeted molecular therapies (TMT) is inevitably hampered by the development of acquired drug resistance in non-small cell lung cancer (NSCLC) treatment. Sonodymanic therapy (SDT) is a promising new cancer treatment approach, but its effects are restricted by tumor hypoxia. Herein, a nanoplatform fabricated by erlotinib-modified chitosan loading sonosensitizer hematoporphyrin (HP) and oxygen-storing agent perfluorooctyl bromide (PFOB), namely CEPH, was developed to deliver HP to erlotinib-sensitive cells. CEPH with ultrasound could alleviate hypoxia inside the three-dimensional multicellular tumor spheroids, suppress NSCLC cell growth under normoxic or hypoxic condition, and enhance TMT/SDT synergistic effects through elevated production of reactive oxygen species, decrease of mitochondrial membrane potential, and down-regulation of the expression of the proteins EGFR, p-EGFR, and HIF-1α. Hence, CEPH could be a potential nanoplatform to improve the efficacy of oxygen-dependent SDT and overcome hypoxia-induced TMT resistance for enhanced synergistic TMT/SDT.

A new antibacterial nano-system based on hematoporphyrin-carboxymethyl chitosan conjugate for enhanced photostability and photodynamic activity

To promote bactericidal activity, improve photostability and safety, novel antibacterial nanoparticle system based on photodynamic action (PDA) was prepared here through conjugation of photosensitizer hematoporphyrin (HP) onto carboxymethyl chitosan (CMCS) via amide linkage and followed by ultrasonic treatment. The system was stable in PBS (pH 7.4) and could effectively inhibit the photodegradation of conjugated HP because of aggregation-caused quenching effect. ROS produced by the conjugated HP under light exposure could change the structure of nanoparticles by oxidizing the CMCS skeleton and thereby significantly promote the photodynamic activity of HP and its photodynamic activity after 6 h was higher than that of HP·2HCl under the same conditions. Antibacterial experiments showed that CMCS-HP nanoparticles had excellent photodynamic antibacterial activity, and the bacterial inhibition rates after 60 min of light exposure were greater than 97%. Safety evaluation exhibited that the nanoparticles were safe to mammalian cells, showing great potential for antibacterial therapy.

Spectroscopic and Theoretical Investigation of β-Lactoglobulin Interactions with Hematoporphyrin and Protoporphyrin IX.

Hematoporphyrin (HP) and protoporphyrin IX (PPIX) are useful porphyrin photosensitizers with significant application values in photodynamic therapy. Currently, many strategies have been developed to improve their clinical performance, such as incorporating them with nanoparticle (NP) carriers. In this work, we studied the possibility of using β-lactoglobulin (BLG) as a potential NP carrier due to their hydrophobic affinity, pH sensitivity, and low cost of extraction and preservation. The interaction mechanisms of BLG with HP and PPIX were investigated using spectroscopic techniques and molecular docking methods. The molecular docking results agree well with the experimental results, which demonstrate that the formations of HP-BLG and PPIX-BLG complexes are endothermic processes and the main acting force is hydrophobic force. Furthermore, the opening–closure states of EF loop have a great influence on the HP-BLG complex formation, where the central hydrophobic cavity of β-barrel is available for HP binding at pH 7.4 but not available at pH 6.2. However, the formation of the PPIX-BLG complex is less dependent on the states of the EF loop, and the binding sites of PPIX are both located on the external surface of BLG under both pH 7.4 and 6.2 conditions. All of our results would provide new insight into the mechanisms of noncovalent interactions between BLG and HP/PPIX. It is believed that this work indicated the potential application values of BLG in designing pH-sensitive carriers for the delivery of HP and PPIX, as well as other poorly soluble drugs.

Sonodynamic therapy of mice breast adenocarcinoma: An in vivo study with hematoporphyrin encapsulated mesoporous silica nanoparticles

ABSTRACTIntroduction: According to high mortality rate due to cancer and side effects of invasive treatments, the noninvasive method such as sonodynamic therapy for breast adenocarcinoma is considerable. Encapsulation of sonosensitizer in nanoparticles can improve the accumulation of these agents in the tumor tissue and decrease in drug side effect. Hence, sonodynamic therapy (SDT) with 1MHz ultrasound (US), hematoporphyrin (HP) and hematoporphyrin encapsulated mesoporous silica nanoparticles (HP-MSN) in breast adenocarcinoma was carried out.Material and Methods: Female Inbred Balb/C mice with grafted breast adenocarcinoma were divided to 16 groups: control, sham, HP (2.5 and 5 mg/kg), HP-MSN (2.5 and 5 mg/kg), 1MHz US (1 and 2 W/cm2), SDT+HP (2.5 and 5 mg/kg) and SDT+HP-MSN (2.5 and 5 mg/kg). The relative volume, tumor growth inhibition ratio (TGI) and the time of tumor growth (T2 and T5-times) evaluated 30-days after treatment.Results: Analysis of data showed the groups of SDT (2 W/cm2)+HP-MSN (5 mg/kg) and SDT (1 W/cm2)+HP-MSN (5 mg/kg) indicated anti-tumor effects from days 18 to 27 after treatment. TGI% in these groups was 45 and 42% respectively and the time of T2 and T5 is greater than that in the control and sham. Kaplan-Meier analysis revealed that the 44-day survival was 95% for the group treated with SDT (2 W/cm2)+HP-MSN (5 mg/kg). All experimental groups had a poorly differentiated grading except of SDT (2 W/cm2)+HP-MSN (5 mg/kg) group which has a moderately differentiated degree based on Bloom-Richardson classification.Conclusion:Based on this study, sonodynamic therapy with 1MHz US (2 W/cm2)+HP-MSN (5 mg/kg) have an anti-tumor effect.

Highly fluorescent hematoporphyrin modified graphene oxide for selective detection of copper ions in aqueous solutions

Here, a highly sensitive and selective copper ion (Cu2+) fluorescence sensor is reported. The Hematoporphyrin functionalized Graphene Oxide (HP-GO) fluorescence sensor were synthesized via esterification reaction between Graphene Oxide and Hematoporphyrin (HP). The HP-GO sensor was fully characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), Scanning Electrom Microscopy (SEM), UV–Vis spectroscopy, Transmission Electron Microscopy (TEM), Fluor meter spectroscopy, X-Ray photoelectron spectroscopy(XPS), and Raman spectroscopy measurements. The HP-GO sensor advertised two linear regions over the range of 0–1.18 × 103 nM and 3.93 × 103 to 47.27 nM of copper (II) with detection limit of 54 nM in the aqueous solution. The selectivity of HP-GO for Cu2+ is much higher than that of other metal ions due to the presence of aza macrocyclic ring on the surface of HP-GO which has a high binding affinity with Cu2+. Additionally, the HP-GO shows wide pH viable range (pH 6–10). The effect of other metal ions on the fluorescence intensity of the HP-GO was also studied and other metal ions show a low interference response in the detection of Cu2+. HP-GO sensor manifests advantages of high reproducibility (The quenched fluorescence of HP/GO-Cu can be recovered by EDTA), attractive long term fluorescence stability (>21 days) in water, also remarkable selectivity regarding number of metal ions (Na+, K+, Ca2+, Fe3+, Fe2+, Al3+, Pb2+, Mn2+, Mg2+, Co2+, Ni2+, Cr6+, Cd2+, Hg2+, and Zn2+), low toxicity and can detect Cu2+ in real water samples which acquire well for its promising in environmental applications.

Immunoconjugates to increase photoinactivation of bovine alphaherpesvirus 1 in semen

Artificial insemination and in vitro embryo production are increasingly used to improve the reproductive efficiency of herds, however success of these techniques depends on the sanitary quality of the semen. Insemination centers commonly use antibiotics in their routine procedure, but they are not able against viruses. In this paper, we demonstrate a new approach for disinfecting virus in bovine semen using photoimmunoinactivation, an adaptation of the photodynamic inactivation (PDI) methodology. The photosensitizers (PSs), hematoporphyrin (HP) and zinc tetracarboxy-phthalocyanine (ZnPc) were conjugated to Immunoglobulin Y (IgY) anti-bovine alphaherpesvirus 1 (BoHV-1) and used for PDI against the BoHV-1 viruses in cell culture and compared to the unconjugated PSs. Both treatments proved to be efficient, but a significant decrease in the irradiation time required to completely eliminate the virus was observed in the samples treated with the immunoconjugates. Photophysical measurements help us to understand the coupling between PSs and IgY and the evaluated production of singlet oxygen. Following the cell culture test, the same approach was applied in semen artificially infected with BoHV-1. The immunoconjugates were also efficient for complete virus inactivation up to 5 min of irradiation and proved to be safe using several parameters of sperm viability, demonstrating the feasibility of our strategy for disinfection viruses in semen.

Sonodynamic Therapy of Mice Breast Adenocarcinoma with HP-MSN

Sonodynamic therapy was appeared as a minimally invasive treatment that is based on the use of low-intensity ultrasound waves with a chemical agent that can be activated by ultrasound (US). The aim of this study was to evaluate the effect of hematoporphyrin (HP) and hematoporphyrin-encapsulated mesoporous silica nanoparticle (HP-MSN) with sonodynamic therapy in an animal model of breast adenocarcinoma. In this study, 96 Balb/C female mice with grafted breast adenocarcinoma were divided to 16 groups each containing 6 mice including: control, sham, HP (2.5 and 5 mg/kg), HP-MSN (2.5 and 5 mg/kg), 3 MHz US (1 and 2 W/cm2), US + HP (2.5 and 5 mg/kg) and US + HP-MSN (2.5 and 5 mg/kg). The tumor relative volume, tumor growth inhibition ratio (TGI), the time of tumor growth (T2 and T5-times) and tumor grading were used to evaluate the treatment outcome. The relative volume parameters and TGI% of 3 MHz US (2 W/cm2) and HP-MSN (5 mg/kg) groups were effective in delaying tumor growth when compared with control and sham at the middle of observation. The time required for tumor to reach two-times (T2) the initial volume in the case of HP-MSN (5 mg/kg) group was greater than that sham and control groups. Analysis of data showed that the groups of US (2 W/cm2) + HP (5 mg/kg), US (1 W/cm2) + HP-MSN (5 mg/kg) and US (2 W/cm2) + HP-MSN (5 mg/kg) indicated antitumor effects from days 18 to 30 after treatment. TGI% in these groups is 54, 45 and 39%, respectively, and the time of T2 and T5 is greater than that in the control and sham. Kaplan–Meier analysis showed that the 45-day survival was 60% for the group treated with US (2 W/cm2) + HP-MSN (5 mg/kg). In histopathological study, all experimental groups had a poorly differentiated grading except of US (2 W/cm2) + HP-MSN (5 mg/kg) group which has a moderately differentiated degree based on Bloom-Richardson classification. Based on the results, we found that sonodynamic therapy with HP-MSN have an antitumor effect on mice breast adenocarcinoma. Conventional treatments for cancer are still far from ideal in terms of systemic toxicity, tumor-selectivity and side effects. Therefore, the development of highly selective and minimally invasive therapies such as sonodynamic therapy is necessary.

Hollow magnetic nanosystem-boosting synergistic effect between magnetic hyperthermia and sonodynamic therapy via modulating reactive oxygen species and heat shock proteins

As a promising treatment modality with spatial and temporal control, alternating magnetic field (AMF) triggered magnetic hyperthermal therapy (MHT) shows broad and promising applications to overcome the drawbacks of traditional focal therapies in combating cancer. However, the MHT efficacy is still not satisfactory with the presence of heat shock proteins (HSPs). In addition, sustained tumor hypoxia haunts practical implications for the treatment of solid tumors. Herein, a novel magnetic nanosystem composed of hollow iron oxide nanoparticles (HIONs), Fe3O4, and sonosensitizers, hematoporphyrin (HP) was rationally designed and successfully synthesized. The hollow HIONs show a large inner cavity for loading sonosensitizer molecules and possess nanozyme activity for catalyzing decomposition of endogenous overexpressed hydrogen peroxide (H2O2) to produce molecular oxygen (O2) that can overcome tumor hypoxia, thus augmenting the sonodynamic therapy (SDT)-induced highly toxic reactive oxygen species (ROS) production for efficient cancer cell apoptosis. Importantly, the generated ROS can also activates the cleavage of HSPs that further eliminate themotolerance and facilitates MHT efficacy. The synergistic catalysis-enhanced SDT efficiency and MHT effect realized most potent tumor suppression efficacy. This work develops a versatile nanoplatform for a multifunctional strategy and broadens the biological applications by rationally designing their structure.

Acanthopanacis Cortex extract: A novel photosensitizer for head and neck squamous cell carcinoma therapy.

The aim of this study was to develop a novel photosensitizer from traditional plant extracts and to investigate the photodynamic therapy (PDT) effect and mechanism of action of the novel photosensitizer on KB and Hep-2 cells. Fluorescence emission, cell viability, and intracellular distribution of candidates were analyzed to screen potential photosensitizers from traditional plant extracts. Cellular reactive oxygen species (ROS) quantification, Annexin V-FITC/PI staining, and western blotting were performed to explore the mechanism of cell death in KB and Hep-2 cells. Of 289 traditional plant extracts, 13 plant extracts with strong fluorescence were initially screened by fluorescence emission analysis. The cell viability assay and intracellular distribution of candidates showed that Acanthopanacis Cortex (AC) extract is a potential photosensitizer. Under optimal PDT conditions, high levels of ROS were produced in KB and Hep-2 cells, followed by cell death. However, there was no significant damage to HaCaT cells. Moreover, apoptosis induced by AC extract with 625 nm irradiation (IR) down-regulated the expression of Bcl-2 protein and up-regulated the expression of Bax protein, as well as that of cleaved PARP-1 protein in both KB and Hep-2 cells. The fluorescence intensity of AC extract at 420 nm is similar to that of the commercial Hematoporphyrin (HP). AC extract with 625 nm IR could enhance the PDT effect, induce ROS generation, and trigger apoptotic pathways in KB and Hep-2 cells. Therefore, we suggest that AC is a potential novel photosensitizer for PDT in head and neck squamous cell carcinoma.

Study of pharmacokinetics and cutaneous photosensitization of hemoporfin in healthy volunteers.

Hemoporfin is a porphyrin-based photosensitizer and has been used for photodynamic therapy of port wine stain birthmarks in China. This study assessed the pharmacokinetics and cutaneous photosensitization of Hemoporfin in healthy volunteers. Sixteen healthy subjects received a single intravenous infusion injection of Hemoporfin (5 mg/kg). The concentrations of Hemoporfin (MHD) and its metabolite Haematoporphyrin (HP) in plasma, urine and faeces were determined. The pharmacokinetic parameters were calculated. In addition, the cutaneous photosensitization was evaluated under the irradiation of solar simulator, 532 nm laser, and sunlight. The Cmax of MHD and HP were 46.7 ± 8.41 and 1.04 ± 0.265 μg/ml, respectively. The t1/2 of MHD and HP were 5.09 ± 0.945 and 5.71 ± 2.65 h, respectively. The AUC0-24h of MHD and HP were 29.8 ± 6.19 and 0.757 ± 0.285 h·μg/ml, respectively. The AUC0-∞ of MHD and HP were 29.8 ± 6.2 and 0.792 ± 0.308 h·μg/ml, respectively. The cumulative fecal excretion rate of MHD and HP were 45.3% and 1.05% at 96 h, respectively. Whereas, the cumulative urinary excretion rate of MHD was only 0.132% at 96 h. The concentration of HP in urine was less than 10% of MHD. After 52 h of administration, the cutaneous photosensitization associated with the exposure to various light sources was minimal. MHD and HP were excreted mainly through the faeces after intravenous infusion. Hemoporfin associated cutaneous photosensitization was insignificant.

Antibacterial application of covalently immobilized photosensitizers on a surface

Singlet oxygen produced by irradiating photosensitizers (PSs) can be used to kill pathogens during water treatment. Chemical immobilization of the PSs on surfaces can maintain their disinfection function long-term. In this study, two model PSs (rose bengal (RB) and hematoporphyrin (HP)) were immobilized on a glass surface using a silane coupling agent with an epoxide group, and their antibacterial properties were analyzed. Fourier transform infrared spectroscopy demonstrated that a covalent bond formed between the epoxide group and hydroxyl group in the PSs. A large proportion of the immobilized PSs (approximately 50%) was active in singlet oxygen production, which was evidenced by a comparative analysis with free PSs. RB was more effective at producing singlet oxygen than HP. The immobilized PSs were durable in terms of repeated use. On the other hand, singlet oxygen produced by the PSs was effective at killing bacteria, mostly for Gram-positive bacteria (> 90% death for 2 h of irradiation), by damaging the cell membrane. The preferable antibacterial property against Gram-positive bacteria compared with that against Gram-negative bacteria suggested efficient penetrability of singlet oxygen across the cell membrane, which led to cell death. Taken together, it was concluded that immobilization of PSs on surfaces using the silane coupling agent proposed in this study was effective at killing Gram-positive bacteria by forming singlet oxygen.

Reactive Oxygen Species-Responsive Nanoparticles Based on PEGlated Prodrug for Targeted Treatment of Oral Tongue Squamous Cell Carcinoma by Combining Photodynamic Therapy and Chemotherapy.

In this study, a reactive oxygen species (ROS)-responsive nanoparticle system was designed for combining photodynamic therapy (PDT) and chemotherapy for oral tongue squamous cell carcinoma (OTSCC)-targeted treatment. A PEGlated prodrug (RPTD) of doxorubicin (DOX) via thioketal linkage and cRGD peptide modification was synthesized and then used to prepare nanoparticles for encapsulating photosensitizer hematoporphyrin (HP). Thus, the obtained HP-loaded RPTD (RPTD/HP) nanoparticles had a regular spherical shape and small size, approximately 180 nm. The RPTD/HP nanoparticles showed a remarkable PDT efficiency and successfully induced ROS generation upon laser irradiation both in vitro and in vivo. DOX exhibited significant ROS-responsive release property from RPTD/HP nanoparticles because of the rupture of the thioketal linker. In OTSCC cells, RPTD/HP nanoparticles were efficiently internalized and showed potent effects on cell growth inhibition and apoptosis induction after laser irradiation. In OTSCC tumor-bearing mice, RPTD/HP nanoparticles displayed excellent tumor-targeting ability and notably suppressed tumor growth through multiple mechanisms after local laser irradiation. Taken together, we supplied a novel therapeutic nanosystem for OTSCC treatment through combining PDT and chemotherapy.

Structure-activity relationship of heme and its analogues in membrane damage and inhibition of fusion.

Under pathological conditions, such as sickle cell disease and malaria, heme concentration increases considerably, and it induces membrane damage. As sickled and normal erythrocytes contain high cholesterol: phospholipid ratio, we investigated the role of lipid composition, chain length, and unsaturation on the partitioning and leakage of hemin in phospholipid vesicles. To establish structure-activity relationship in membrane damage, experiments with two other analogues, protoporphyrin-IX and hematoporphyrin (HP) were also carried out. Hemin and its analogues localize differently in membranes and exhibit distinct roles in partitioning, leakage and fusion. Hemin and HP trigger more leakage in the presence of aminophospholipids, whereas cholesterol buffers the destabilizing effect remarkably. Inhibition of fusion by hemin further suggests its unexplored and important role in membrane trafficking, particularly under diseased conditions.