Photodynamic Treatment Research Articles

Photodynamic therapy for prostate cancer: Recent advances, challenges and opportunities.

Over the past two decades, there has been a tendency toward early diagnosis of prostate cancer due to raised awareness among the general public and professionals, as well as the promotion of prostate-specific antigen (PSA) screening. As a result, patients with prostate cancer are detected at an earlier stage. Due to the risks of urine incontinence, erectile dysfunction, etc., surgery is not advised because the tumor is so small at this early stage. Doctors typically only advise active surveillance. However, it will bring negative psychological effects on patients, such as anxiety. And there is a higher chance of cancer progression. Focal therapy has received increasing attention as an alternative option between active monitoring and radical therapy. Due to its minimally invasive, oncological safety, low toxicity, minimal effects on functional outcomes and support by level 1 evidence from the only RCT within the focal therapy literature, photodynamic treatment (PDT) holds significant promise as the focal therapy of choice over other modalities for men with localized prostate cancer. However, there are still numerous obstacles that prevent further advancement. The review that follows provides an overview of the preclinical and clinical published research on PDT for prostate cancer from 1999 to the present. It focuses on clinical applications of PDT and innovative techniques and technologies that address current problems, especially the use of nanoparticle photosensitizers in PDT of prostate cancer.

Hepatitis E virus is effectively inactivated by methylene blue plus light treatment.

Photodynamic treatment with methylene blue (MB) and visible light is a well-established pathogen inactivation system for human plasma. This technique is routinely used in different countries. MB/light treatment was shown to inactivate several transfusion-transmittable viruses, but its efficiency for the inactivation of the quasi-enveloped hepatitis E virus (HEV) has not yet been investigated. Plasma units were spiked with cell culture-derived HEV and treated with the THERAFLEX MB-Plasma system using various light doses (30, 60, 90, and 120 J/cm2 ). HEV titers in pre- and post-treatment samples were determined by virus titration and a large-volume plating assay to improve the detection limit of the virus assay. THERAFLEX MB-Plasma efficiently inactivated HEV in human plasma. Even the lowest light dose of 30 J/cm2 inactivated HEV down to the limit of detection, with a mean log reduction factor of greater than 2.4 for the total process. Our study demonstrates that the THERAFLEX MB-Plasma system effectively inactivates HEV in human plasma.

A monoamine oxidase-A inhibitor phthalocyanine conjugate for targeted photodynamic therapy and inhibition of prostate cancer metastasis in vitro

Photodynamic therapy (PDT), as an alternative non-invasive clinical treatment modality, has been extensively employed for various anticancer applications in preclinical and clinical trials. However, there is hardly any PDT research based on invasive or metastatic tumors. But it can't be ignored that cancer metastases are responsible for 90% of all cancer-related death. Among these metastatic cancers, prostate cancer (PCa) is regarded as one of the leading causes of cancer related deaths amongst male patients due to its high metastasis and high fatality rate. At present, it remains a great challenge to apply traditional PDT technology for inhibiting prostate cancer metastasis. In this work, we successfully designed and synthesized a novel MAO-A targeted photosensitizer Pc-MLB for targeted photodynamic treatment of prostate cancer and inhibiting its metastasis in vitro. In vitro experiments demonstrate that Pc-MLB shows high target affinity and specificity towards prostate cancer cells and remarkable photodynamic anticancer activity compared with the control. More significantly, the migration and invasion assays show that Pc-MLB exhibits the ability to inhibit the migration and metastasis of prostate cancer cells to some extent.

Photodynamic inactivation of multidrug-resistant bacteria in wastewater effluent using green phytochemicals as a natural photosensitizer

The control of multidrug-resistant bacteria (MDRB) is a great challenge in the 21st century. Photodynamic treatment (PDT) is one of the promising approaches to control MDRB. In the process, powerful oxidants such as reactive oxygen species (ROS) are produced, which cause cytotoxic damage and cell death of bacteria. This study examined a new and environment-friendly strategy for the photodynamic inactivation of two MDRB (Escherichia coli and Staphylococcus aureus) and total coliform (TC) in wastewater effluent using two phytochemicals, pyrogallol (PGL) and terpinolene (TPN), along with white and blue light-emitting diode (LED) light. Fourier-transform infrared spectroscopy (FTIR) of the phytochemicals confirmed the presence of different phenolic and aromatic compounds, which can enhance the generation of ROS alongside inactivating the bacterial cells. In the PDT process, white LED light was more active in controlling MDRB than blue LED light. After 80 min irradiation with white LED light (17 mW/cm2), the MDRB bacteria were eradicated completely at a minimum inhibitory concentration (MIC) dose (0.156 mg/mL for E. coli and 0.078 mg/mL for S. aureus) of PGL. In addition, light intensity was an important parameter in photodynamic disinfection. The TC in the secondary effluent was inactivated completely by both phytochemicals after 60 min of exposure to white LED light with an intensity of 80 mW/cm2. The photosensitizing activity of phytochemicals was analyzed by a bactericidal and imidazole-RNO assay. These assays showed that PGL contributed to the generation of •OH radicals, whereas TPN produced 1O2 in the PDT process. Transmission electron microscopy (TEM) confirmed bacterial cell disruption after treatment. Overall, PDT using the phytochemicals as PS is a sustainable approach to control the MDRB and TC in wastewater successfully.

Synchronous enhancement of upconversion and NIR-IIb photoluminescence of rare-earth nanoprobes for theranostics.

This study develops a multifunctional molecular optical nanoprobe (SiO2@Gd2O3: Yb3+/Er3+/Li+@Ce6/MC540) with a unique core-satellite form. The rare-earth doped nanodots with good crystallinity are uniformly embedded on the surface of a hydrophilic silica core, and the nanoprobe can emit near-infrared-IIb (NIR-IIb) luminescence for imaging as well as visible light that perfectly matches the absorption bands of two included photosensitizers under 980 nm irradiation. The optimal NIR-IIb emission and upconversion efficiency are attainable via regulating the doping ratios of Yb3+, Er3+ and Li+ ions. The relevant energy transfer mechanism was addressed theoretically that underpins rare-earth photoluminescence where energy back-transfer and cross relaxation processes play pivotal roles. The nanoprobe can achieve an excellent dual-drive photodynamic treatment performance, verified by singlet oxygen detections and live-dead cells imaging assays, with a synergistic effect. And a brightest NIR-IIb imaging was attained in tumoral site of mouse. The nanoprobe has a high potential to serve as a new type of optical theranostic agent for tumor.

Photodynamic antibacterial and antibiofilm activity of riboflavin against Xanthomonas oryzae pv oryzae: an ecofriendly strategy to combat bacterial leaf blight (BLB) rice disease.

Bacterial leaf blight (BLB), caused by Xanthomonas oryzae pv oryzae (Xoo), is one of the most damaging rice diseases, causing severe production losses depending on the rice variety. The purpose of this study was to develop an antibacterial photodynamic treatment (aPDT) using riboflavin for the treatment of BLB disease. Combining light and riboflavin (RF) therapy significantly reduced bacterial planktonic cells compared to RF alone. Photoactivated riboflavin also decreased biofilm biomass by reducing the number of viable sessile cells and the production of extracellular polymeric substances (EPS). Reactive oxygen species (ROS) levels in Xoo cells treated with photoactivated riboflavin were found to be significantly higher than in cells treated with riboflavin and light individually. Malondialdehyde (MDA) increased greatly in photoactivated riboflavin treated cells, indicating that severe oxidative damage was induced. Subsequently, a reduction in lactate dehydrogenase (LDH) activity in photoactivated riboflavin treated Xoo cells indicates that oxidative stress has disrupted the respiratory system, leading to bacterial cell death. In an ex vivo aPDT assay, photoactivated riboflavin successfully eradicated Xoo on the surface of rice leaves. Photoactivated riboflavin had no side effects on rice seed germination in subsequent trials, indicating that it is safe for agricultural applications. Therefore, all these findings suggest that aPDT is a potential alternative management strategy for BLB disease.

Gold-based nanoparticles realize photothermal and photodynamic synergistic treatment of liver cancer and improve the anaerobic tumor microenvironment under near-infrared light.

In order to solve the different pains caused by traditional cancer treatment methods such as surgical treatment, the nano-drug delivery system provides new ideas for cancer treatment. In this paper, a novel anti-tumor therapy nanoparticle, P(AAm-co-AN)-AuNRs@CeO2-Ce6(PA/Ce6), is prepared, which provides a novel idea for liver cancer treatment. The CeO2-coated gold nanorods were grafted onto the surface of the temperature-sensitive polymer P(AAm-co-AN)-CTPD. The photosensitizer Ce6 is loaded on the surface of the nanoparticles and the polymer layer. CeO2 can effectively alleviate the tumor anaerobic microenvironment, and under 808 nm near-infrared (NIR) excitation, the gold nanorods achieve photothermal conversion to induce local heating, which leads to the phase transition of the polymer layer and realizes a controllable release mechanism. In addition, 660 nm NIR light can effectively induce Ce6 to produce singlet oxygen, thereby effectively killing cancer cells. Under the 808 nm laser irradiation within 600 s, the PA/Ce6 solution can heat up to about 60°C, which was enough to ablate both cancer cells and tumor tissues. When the temperature was 50°C, the cumulative release rate of Ce6 was 95.31%. Under the 808 nm laser irradiation, oxygen production capacity of PA/Ce6 was higher and can effectively reduce the content of hydrogen peroxide in cancer cells. Compared to free Ce6, the reactive oxygen species-mediated fluorescence of PA/Ce6 nanoparticles was greater. The cell viability and migration of HepG2 cells were decreased after the 660 and 880 nm lasers were irradiated at the same time. The cancer cells were further inhibited, showing a good in vitro anti-tumor effect. PA-DOX showed the best tumor growth inhibitory effect under NIR laser irradiation and had no acute toxicity in vivo. Due to the existence of AuNRs, nanoparticles had high-efficiency photothermal conversion ability to achieve photothermal therapy. Ce6 can generate singlet oxygen under the excitation of 660 nm laser to realize photodynamic therapy. The experimental results also showed that PA/Ce6 can effectively decompose hydrogen peroxide under laser irradiation, aiming to effectively alleviate the anaerobic microenvironment of tumors. These indicate that PA/Ce6 plays a promising role for hepatocellular carcinoma treatment.

Disruption of Calcium Homeostasis and Following Changes in Calcium Signaling in Neurons and Glial Cells in Response to Photodynamic Treatment

Disruption of Calcium Homeostasis and Following Changes in Calcium Signaling in Neurons and Glial Cells in Response to Photodynamic Treatment

Antimicrobial photodynamic inactivation of wastewater microorganisms by halogenated indole derivative capped zinc oxide

Novel 5-bromoindole (5B)-capped zinc oxide (ZnO) nanoparticles (5BZN) were synthesized to improve the antibacterial, antibiofilm, and disinfection processes for the control of microorganisms in wastewater treatment. When exposed to 5BZN, the biofilm density and cell attachment were reduced dramatically, as measured by scanning electron microscopy (SEM). The 5BZN were also investigated for photodynamic treatment of multidrug-resistant (MDR) bacteria and toxicity. The combination of 5B and ZnO exhibited strong antibacterial and antibiofilm activities against MDR bacteria even at low doses (20 μg/mL). After 12.5 mW/cm2 blue LED irradiation, the composite 5BZN showed superior photodynamic inactivation of two wastewater MDR, Enterobacter tabaci E2 and Klebsiella quasipneumoniae SC3, with cell densities reduced by 3.9 log CFU/mL and 4.7 log CFU/mL, respectively, after 120 min. The mechanism of bacterial inactivation was studied using a scavenging investigation, and H2O2 was identified mainly as the reactive species for bacterial inactivation. The 5BZN exhibited higher photodynamic inactivation towards the total coliform bacteria in wastewater effluents under a blue LED light intensity of 12.5 mW/cm2 with almost complete inactivation of the coliform bacteria cells within 40 min. Furthermore, when 5BZN (100 mg/L) was added to the reactor, the level of tetracycline antibiotic degradation was increased by 63.6% after 120 min. The toxicity test, animal model nematode studies and seed germination assays, showed that 5BZN is harmless, highlighting its tremendous potential as a self-healing agent in large-scale photodynamic disinfection processes.

Enhancement of the cytotoxic effect of dihydroartemisinin in high-risk human papillomavirus-infected cells by aminolevulinic acid via the Bax/Bcl-2-caspase pathway

BackgroundTraditional treatments for human papillomavirus-related cutaneous diseases include 5-aminolevulinic acid photodynamic therapy, cryotherapy, microwave ablation, and surgical resection. These treatment methods involvevarious adverse reactions; therefore, it remains necessary to explore new treatment methods. Dihydroartemisinin shows cytotoxic effects against several malignancies by producing reactive oxygen species, and heme environments reportedly enhance its activity. However, the underlying mechanismsare still unclear. Therefore, we investigated the mechanism of dihydroartemisininin inhuman papillomavirus-infected cells. MethodsHeLa cells were treated with dihydroartemisinin, 5-aminolevulinic acid, and succinylacetone. The cell viability, apoptosis, mitochondrial membrane potential, and reactive oxygen species levels were investigated, and via western blotting analysis and polymerase chain reaction, dihydroartemisinin activity-related pathways were also determined. ResultsDihydroartemisinin inhibited HeLa cell proliferation and promoted cell apoptosis via the Bax/Bcl-2-Caspase pathway in a concentration-dependent manner. The specific cytotoxicity toward HeLa cells was enhanced by the addition of 5-aminolevulinic acid, a clinically used heme-synthesis precursor, owing to an increase in heme levels. Conversely, following the addition of succinylacetone, a heme synthesis blocker, heme levels decreased. Furthermore, dihydroartemisinin significantly increased reactive oxygen species levels as intracellular heme synthesis increased. Moreover, photodynamic therapy following dihydroartemisinin and 5-aminolevulinic acid treatment further enhanced the cytotoxic effect of dihydroartemisinin on high-risk human papillomavirus-infected cells. ConclusionsDihydroartemisinin exerts acytotoxic effect on high-risk human papillomavirus-infected cells by modulating heme levels via the Bax/Bcl–2-Caspase pathway, and the dihydroartemisinin, 5-aminolevulinic acid, photodynamic therapy combination treatment significantly enhanced its cytotoxic effect on human papillomavirus-infected cells.

Of the efficacy of pharmacotherapy in photodynamic antibacterial treatment of dissolved purulent peritonitis

Despite the development of medicine, especially surgery (diagnostics, methods of surgery, postoperative measures, development of new technologies), many questions still remain unresolved and are awaiting their answers. Spilled purulent peritonitis has been and remains a formidable pathology in abdominal surgery which still requires research, development of new treatment methods and innovative ways of cleansing from pathogenic cells of the abdominal cavity, which help to improve the results of treatment of spilled purulent peritonitis.

Light-activated antibacterial electrospun polyacrylonitrile-graphene quantum dot nanofibrous membranes

Polyacrylonitrile (PAN) nanofibrous membranes incorporating graphene quantum dots (GQD) as photoantibacterial additives were prepared by electrospinning. GQD encapsulation in the composite GQD-PAN membranes proved very stable, with negligible GQD leakage after 1 month immersed in neutral phosphate buffer solutions. A series of GQD-PAN membranes with different GQD content and electrospinning times were prepared to assess the influence of these parameters on the antibacterial activity of the membranes against Escherichia coli under visible light irradiation. Electrospinning time had a pronounced effect on membrane weight/thickness and nanofiber diameter, both parameters increasing with electrospinning time. Membranes with the optimal composition (1% wt. GQD and 1.5 h electrospinning time) showed excellent antibacterial activity against E. coli, with 99.9999% (6 logaritmic units) bacterial inactivation after 24 h illumination with visible light. Different bactericidal reactive oxygen species (ROS) were detected upon illumination of GQD solutions and GQD-PAN membranes, confirming photodynamic inactivation of the bacteria by GQD photosensitization. In terms of ROS production, GQD outperformed well-known photosensitizers crystal violet and toluidine blue O, both with long-established efficiency for photodynamic treatment of drug-resistant bacterial infections.

Nitrogen-doped carbon dots/curcumin nanocomposite for combined Photodynamic/photothermal dual-mode antibacterial therapy

Due to their excellent photophysical properties, carbon quantum dots have great potential in biomedical and drug delivery fields. In this study, nitrogen-doped carbon quantum dots with good water solubility were prepared using citric acid and ethylenediamine as precursors, and compounded with curcumin, a photosensitive component, to produce composite nanomaterials with photodynamic therapy and synergistic photothermal therapy. The formation of nitrogen-doped carbon quantum dots and composite nanomaterials was verified using physical and optical means. In addition, the composite nanomaterials produced single-linear oxygen and exacerbated the increase of solution temperature under blue (405 nm) and near-infrared (808 nm) light irradiation, respectively. The plate counting method showed that the composite nanomaterials exhibited good photodynamic synergistic photothermal antibacterial properties against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus under dual light source (405+808 nm) irradiation, which improved the photoinactivation of curcumin against bacteria. In addition, the composite nanomaterials exhibited low toxicity and good hemocompatibility. These experimental results suggested that the composite nanomaterials showed great potential in a multimodal photodynamic therapy synergistic photothermal treatment platform.

Human Enamel Fluorination Enhancement by Photodynamic Laser Treatment.

Poor oral hygiene leads to serious damages of theteeth’s surface enamel such as micro-abrasions and acid erosion. These alterations combined with bacterial plaque result in cavity appearance. Prophylactic measures include various techniques for enamel surface restoration. Fluorination is one of the most important treatments for this purpose. Therefore, in the present research, we investigated the classical fluorination treatment compared with laser photodynamic fluorination performed on human enamel samples with poor surface quality. Three sample groups were investigated: veneer (F), inlay (I), and crowns (C). The general morphologic aspect was investigated by scanning electron microscopy (SEM), and the specific details such as the fine microstructure and nanostructure were investigated by atomic force microscopy (AFM) of the surface roughness. The samples were also investigated by Fourier transformed infrared attenuated total reflectance (FTIR-ATR) to evidence the fluorination effect on the enamel surface. Results showed that all initial samples had an altered state with micro-abrasions and erosion with mineral loss, which increase the surface roughness. The F group was the most damaged, having a higher roughness, and the I group was less damaged. Classic fluorination treatment partially restored the enamel by local re-mineralization, but did not obtain the parameters of healthy enamel. However, a significant decrease of the roughness was observed (statistical relevance p = 0.001 with the Breusch–Pagan Test). This fact was supported by the presence of newly formed fluorides in the FTIR-ATR spectra. The photodynamic laser fluorination restores the enamel in an enhanced manner by a strong re-mineralization, which implies a significant roughness value decrease comparable to healthy enamel. The Breusch–Pagan Test confirmed the relevance with p = 0.001. This is due to an extended re-mineralization abundant in fluoride crystals as observed by AFM and FTIR. Statistical p-values regarding laser application were in the range of 0.02–0.06, supporting its relevance in the fluorination effect. The final conclusion is that the photodynamic effect is able to favor the newly formed fluoride deposition onto the affected sites of the enamel surface.

Retinal and choroidal vasoreactivity in central serous chorioretinopathy.

This study aims to investigate retinal and choroidal vascular reactivity to carbogen in central serous chorioretinopathy (CSC) patients. An experimental pilot study including 68 eyes from 20 CSC patients and 14 age and sex-matched controls was performed. The participants inhaled carbogen (5% CO2 + 95% O2) for 2min through a high-concentration disposable mask. A 30° disc-centered fundus imaging using infra-red (IR) and macular spectral domain optical coherence tomography (SD-OCT) using the enhanced depth imaging (EDI) technique was performed, both at baseline and after a 2-min gas exposure. A parametric model fitting-based approach for automatic retinal blood vessel caliber estimation was used to assess the mean variation in both arterial and venous vasculature. Choroidal thickness was measured in two different ways: the subfoveal choroidal thickness (SFCT) was calculated using a manual caliper and the mean central choroidal thickness (MCCT) was assessed using an automatic software. No significant differences were detected in baseline hemodynamic parameters between both groups. A significant positive correlation was found between the participants' age and arterial diameter variation (p < 0.001, r = 0.447), meaning that younger participants presented a more vasoconstrictive response (negative variation) than older ones. No significant differences were detected in the vasoreactive response between CSC and controls for both arterial and venous vessels (p = 0.63 and p = 0.85, respectively). Although the vascular reactivity was not related to the activity of CSC, it was related to the time of disease, for both the arterial (p = 0.02, r = 0.381) and venous (p = 0.001, r = 0.530) beds. SFCT and MCCT were highly correlated (r = 0.830, p < 0.001). Both SFCT and MCCT significantly increased in CSC patients (p < 0.001 and p < 0.001) but not in controls (p = 0.059 and 0.247). A significant negative correlation between CSC patients' age and MCCT variation (r = - 0.340, p = 0.049) was detected. In CSC patients, the choroidal thickness variation was not related to the activity state, time of disease, or previous photodynamic treatment. Vasoreactivity to carbogen was similar in the retinal vessels but significantly higher in the choroidal vessels of CSC patients when compared to controls, strengthening the hypothesis of a choroidal regulation dysfunction in this pathology.

Development of novel porphyrin/combretastatin A-4 conjugates for bimodal chemo and photodynamic therapy: Synthesis, photophysical and TDDFT computational studies

Anticancer photodynamic therapy (PDT) in recent years has gained attention among therapists due to its low systemic toxicity and non-invasive nature. Today, one of the big trends in the development of photosensitizers for photodynamic therapy is a construction of advanced multifunctional molecules, which can overcome known problems for conventional drugs. In this paper, we made an attempt to create bimodal conjugates consisting of a meso-tetraphenylporphyrin (photosensitizer) and E-combretastatin A-4 (chemotherapeutic drug), which under light irradiation could: 1) participate in photodynamic treatment by ROS generation; 2) participate in chemotherapy by liberation of low-toxic E-combretastatin A-4 followed by its photoisomerization into more cytotoxic Z-combretastatin A-4. We believe, that such conjugates should demonstrate a low dark toxicity and significant light-induced antitumor properties due to step-by-step transformation of E-combretastatin A-4 into Z-combretastatin A-4. Thus, we describe the design, synthesis, photophysical and TDDFT computational studies for the new class of porphyrin/combretastatin A-4 conjugates.

Vision Defense: Efficient Antibacterial AIEgens Induced Early Immune Response for Bacterial Endophthalmitis.

Bacterial endophthalmitis (BE) is an acute eye infection and potentially irreversible blinding ocular disease. The empirical intravitreous injection of antibiotic is the primary treatment once diagnosed as BE. However, the overuse of antibiotic contributes to the drug resistance of pathogens and the retinal toxicity of antibiotic limits its application in clinic. Herein, a cationic aggregation‐induced emission luminogens named with triphenylamine thiophen pyridinium (TTPy) is reported for photodynamic treatment of BE. TTPy can selectively discriminate and kill bacteria efficiently over normal ocular cells. More importantly, TTPy shows excellent antibacterial ability in BE rat models infected by Staphylococcus aureus. Meanwhile, the bacterial killing behavior triggered by TTPy induces innate immune response at an early stage of infection, limiting subsequent robust inflammation and protecting retina from bacterial toxins and inflammation‐induced bystander damage. In addition, TTPy performs better antibacterial ability than commercially used Rose Bengal, suggesting its excellent capability of vision salvage in acute BE. This study exhibits an efficient photodynamic antibacterial treatment to BE, which induces an early intraocular immune response and saves useful vision, endowing TTPy a promising potential for clinical application of ocular infections.

Effects of curcumin‐based photodynamic treatment combined with low‐temperature storage on shelf life and purine content of Litopenaeus vannamei

In this study, the effects of photodynamic treatment on the shelf life and purine content of Litopenaeus vannamei under low-temperature storage conditions were investigated. Indicators of shelf life were detected to evaluate the shelf life, and the change of purine content during storage detected by HPLC. The results showed that compared with cold storage, the shelf life of shrimp was extended from 3 days to 8 days with the treatment of microcrystalline storage. Moreover, the shelf life of shrimp was extended to 12 days when stored with the photodynamic treatment combined with microcrystalline storage (PDT + MT). The content of hypoxanthine decreased significantly after 24 h storage, which may be related to the inhibition of 5′-NT, PNP, ADA, and XOD activities. This study provided scientific support for the popularization and application of photodynamic technology in the storage of shrimp. Novelty impact statement Photodynamic technology is helpful to prolong the shelf life of shrimp during low-temperature. Photodynamic combined with low-temperature can affect purine content by affecting purine metabolism enzymes.

A NTR and O2 programmed responsive photogenic radicals for efficient hypoxia cancer therapy

Stimulus responsive photodynamic therapy has attracted much attention. Although many methods have been proposed to alleviate the impact of hypoxia on photodynamic therapy (PDT), hypoxia is still one of the biggest obstacles to the efficient photodynamic treatment of tumors. Herein, a novel kind of nitroreductase (NTR) and O2 programmed responsive photosensitizer Eos-NO2 was developed to achieve precise and efficient PDT of hypoxia tumor. Specifically, the PDT “off” state Eos-NO2 was activated by the overexpressed NTR in tumor region to form PDT “on” state Eos. Then, the produced Eos in hypoxia could further generate the active free radicals and singlet oxygen for the efficient treatment of hypoxic tumors owing to photo-induced free radical process. Both in vitro and in vivo results confirm that such a NTR and O2 programmed responsive photosensitizer Eos-NO2 shows high specificity and selectivity for hypoxic solid tumor, presenting good prospects in the clinical cancer phototherapy.

Dual-Target Multifunctional Superparamagnetic Cationic Nanoliposomes for Multimodal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy of Retinoblastoma.

BackgroundWith high malignancy, retinoblastoma (RB) commonly occurs in infants and has incredible difficulty with the early diagnosis. In recent years, the integrated theranostics of multimodal imaging-guided therapy has shown promising potential for oncotherapy.PurposeTo prepare folate/magnetic dual-target theranostic nanoparticles integrating with US/PA/MR imaging and the synergistic photothermal treatment (PTT)/photodynamic treatment (PDT) for the early diagnosis and timely intervention of RB cancer.MethodsFolate/magnetic dual-target cationic nanoliposomes (CN) encapsulating indocyanine green (ICG) and perfluorohexane(PFH)(FA-CN-PFH-ICG-Fe3O4, FCNPIFE) were synthesized and characterized. Then we evaluated their targeting ability, US/PA/MR imaging effects, and the efficacy of synergistic PTT/PDT in vitro and in vivo. Finally, we explored the mechanism of synergistic PTT/PDT in Y79 tumor-bearing mice.ResultsFCNPIFEs were stable and uniform in 7 days. They showed excellent in vitro targeting ability with a 95.29% cell uptake rate. The in vitro US/PA/MRI imaging results of FCNPIFEs showed a concentration-dependent manner, and in vitro therapy FCNPIFEs exhibited an enhanced anticancer efficacy against Y79 cells. In vivo analysis confirmed that FCNPIFEs enabled a targeted synergistic PTT/PDT under US/PA/MR imaging guidance in Y79 tumor-bearing mice, achieving almost complete tumor regression. Immunofluorescence results displayed weaker fluorescence intensity compared with other single treatment groups, confirming that PTT/PDT synergistic therapy effect was achieved by down-regulating the expression of HIF-1α and HSP70.ConclusionFCNPIFEs were verified as promising theranostic nanoliposomes for RB oncotherapy and showed great potential in clinical application.