Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen H
PROVIDER: S-EPMC5233724 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
Publications
Nanoscintillator-mediated X-ray inducible photodynamic therapy for in vivo cancer treatment.
Chen Hongmin H Wang Geoffrey D GD Chuang Yen-Jun YJ Zhen Zipeng Z Chen Xiaoyuan X Biddinger Paul P Hao Zhonglin Z Liu Feng F Shen Baozhong B Pan Zhengwei Z Xie Jin J
Nano letters 20150312 4
Photodynamic therapy is a promising treatment method, but its applications are limited by the shallow penetration of visible light. Here, we report a novel X-ray inducible photodynamic therapy (X-PDT) approach that allows PDT to be regulated by X-rays. Upon X-ray irradiation, the integrated nanosystem, comprised of a core of a nanoscintillator and a mesoporous silica coating loaded with photosensitizers, converts X-ray photons to visible photons to activate the photosensitizers and cause efficie ...[more]
Similar Datasets
Project description:Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer.
| S-EPMC5118595 | biostudies-literature
Project description:Calreticulin is recognized as one of the pivotal damage-associated molecular pattern molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT). The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4?mg/mouse) was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT-vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT-vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor response elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.
| S-EPMC4315177 | biostudies-literature
Project description:Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photosensitizers to tumors. O2, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O2 to sustain their growth and that often leads to low O2 levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)-facilitated PDT, or RBC-PDT, is introduced that can potentially solve the issue. As the name tells, RBC-PDT harnesses erythrocytes, an O2 transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry-on O2 source, RBC-PDT can efficiently produce 1O2 even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC-PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O2 and photosensitizers. Overall, RBC-PDT is expected to find wide applications in modern oncology.
| S-EPMC6867707 | biostudies-literature
Project description:An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm3) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.
| S-EPMC5816188 | biostudies-literature
Project description:Photodynamic therapy (PDT) has shown great effectiveness in oncotherapy but has not been implemented in broad clinical applications because the limited penetration depth of the light used has been unable to reach deep-seated tumors. However, X-rays have been widely used in the clinical field for imaging and radiation therapy due to their excellent tissue penetration depth. Recently, X-rays have been established as an ideal excitation source for PDT, which holds great promise for breaking the depth limitation of traditional PDT for treatment of deep-seated tumors. This review aims to provide an overview of nanoscintillator-mediated X-ray induced PDT (X-PDT) including the concept, the design considerations of nanosensitizers for X-PDT, the modelling of nanosensitizer energy deposition, the putative mechanism by which X-PDT kills cells, and the prospects of future directions. We attempt to summarize the main developments that have occurred over the past decades. Possibilities and challenges for the clinical translation of X-PDT are also discussed.
| S-EPMC6956812 | biostudies-literature
Project description:Recent efforts to develop tumor-targeted photodynamic therapy (PDT) photosensitizers (PSs) have greatly advanced the potential of PDT in cancer therapy, although complete eradication of tumor cells by PDT alone remains challenging. As a way to improve PDT efficacy, we report a new combinatory PDT therapy technique that specifically targets multilayers of cells. Simply mixing different PDT PSs, even those that target distinct receptors (this may still lead to similar cell-killing pathways), may not achieve ideal therapeutic outcomes. Instead, significantly improved outcomes likely require synergistic therapies that target various cellular pathways. In this study, we target two proteins upregulated in cancers: the cannabinoid CB2 receptor (CB2R, a G-protein coupled receptor) and translocator protein (TSPO, a mitochondria membrane receptor). We found that the CB2R-targeted PS, IR700DX-mbc94, triggered necrotic cell death upon light irradiation, whereas PDT with the TSPO-targeted IR700DX-6T agent led to apoptotic cell death. Both PSs significantly inhibited tumor growth in vivo in a target-specific manner. As expected, the combined CB2R- and TSPO-PDT resulted in enhanced cell killing efficacy and tumor inhibition with lower drug dose. The median survival time of animals with multilayer PDT treatment was extended by as much as 2.8-fold over single PDT treatment. Overall, multilayer PDT provides new opportunities to treat cancers with high efficacy and low side effects.Statement of significancePhotodynamic therapy (PDT) is increasingly used as a minimally invasive, controllable and effective therapeutic procedure for cancer treatment. However, complete eradication of tumor cells by PDT alone remains challenging. In this study, we investigate the potential of multilayer PDT in cancer treatment with high efficacy and low side effects. Through PDT targeting two cancer biomarkers located at distinct subcellular localizations, remarkable synergistic effects in cancer cell killing and tumor inhibition were observed in both in vitro and in vivo experiments. This strategy may be widely applied to treat various cancer types by using strategically designed PDT photosensitizers that target corresponding upregulated receptors at tactical subcellular localization.
| S-EPMC5415343 | biostudies-literature
Project description:Introduction: The photosensitizer, meso-tetraphenyl chlorine disulphonate, TPCS2a (Amphinex®) has been evaluated in a proteome analysis of rat bladder cancer cells (AY27) in combination with the chemotherapeutic drug Bleomycin (BML). Photochemical internalization (PCI) is a novel technology for cytosolic delivery of macromolecular therapeutics based on principles of photodynamic therapy (PDT). Since tumor cells have shown to release certain proteins into plasma membrane after PDT1, the we aimed at of this study was to quantifying the amount of endosomal proteins expressed following TPCS2a-PDT or BLM/TPCS2a-based PCI. Methods: AY27 cells were grown in isotopically labeled SILAC medium using the SILAC technology and further incubated with TPCS2a followed by BLM stimulation and blue light illumination (LumiSource, 13mW/cm2). Endosomal proteins were enriched by gradient-ultracentrifugation and measurements of BLM after endosomal uptake were performed by high pressure liquid chromatography (HPLC). Quantitative measurements of the pProteins were performed quantified by Orbitrap mass spectrometry (LC-MS/MS). These rRaw data files were analyzed using Max Quant v 1.5.5.12 thereby, mapping the spectra over rat canonical proteome with isoforms 3. The SILAC ratios hence obtained were log transformed and subjected to Student’s t-test in order to find identify differentially expressed proteins (DEPs) using Perseus platform4. Further these DEPs were mapped to Gene Ontology database to characterize the enrichment of ontological categories. Results: Both upregulated and downregulated DEPs were recorded from total cell extracts as well as from enriched endosomes after gradient-ultracentrifugation and further grouped according to their biological functions. Conclusions: The present work shows that SILAC analysis for in vitro PDT and PCI treatment is a promising technology approach for characterizing different processes related to e.g. cell death during PDT/PCI5 treatment based on quantified DEPs in these different conditions, respectively.
2024-06-07 | PXD006915 | Pride
Project description:Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber. This TLD1433-mediated PDT induced an EC50 of 1.98 μM (J/cm2) and 4807 μM (J/cm2) for green and red light, respectively. Cells were then treated with 10 µM TLD1433 in a 96-well plate with the OSA using two 2-cm radial diffusers, each transmitted 532 nm light at 50 mW/cm for 278 s. Monte Carlo simulations of the surface light propagation from the OSA computed light fluence (J/cm2) and irradiance (mW/cm2) distribution. In regions where 100% loss in cell viability was measured, the simulations suggest that >20 J/cm2 of 532 nm was delivered. Our studies indicate that TLD1433-mediated PDT with the OSA and light simulations have the potential to become a platform for treatment planning for IO-PDT.
| S-EPMC7407920 | biostudies-literature
Project description:In this work, we brought together two existing clinical techniques used in cancer treatment-X-ray radiation and photodynamic therapy (PDT), whose combination termed X-PDT uniquely allows PDT to be therapeutically effective in deep tissue. To this end, we developed mitochondrially targeted biodegradable polymer poly(lactic-co-glycolic acid) nanocarriers incorporating a photosensitizer verteporfin, ultrasmall (2-5 nm) gold nanoparticles as radiation enhancers, and triphenylphosphonium acting as the mitochondrial targeting moiety. The average size of the nanocarriers was about 160 nm. Upon X-ray radiation our nanocarriers generated cytotoxic amounts of singlet oxygen within the mitochondria, triggering the loss of membrane potential and mitochondria-related apoptosis of cancer cells. Our X-PDT strategy effectively controlled tumor growth with only a fraction of radiotherapy dose (4 Gy) and improved the survival rate of a mouse model bearing colorectal cancer cells. In vivo data indicate that our X-PDT treatment is cytoreductive, antiproliferative, and profibrotic. The nanocarriers induce radiosensitization effectively, which makes it possible to amplify the effects of radiation. A radiation dose of 4 Gy combined with our nanocarriers allows equivalent control of tumor growth as 12 Gy of radiation, but with greatly reduced radiation side effects (significant weight loss and resultant death).
| S-EPMC7256935 | biostudies-literature
Project description:In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional--PDT and imaging--gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species--singlet oxygen--before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of "precision medicine" in line with stem cell and gene therapies as tools in cancer therapy.
| S-EPMC4280627 | biostudies-literature