An intelligent nanodevice based on the synergistic effect of telomerase-triggered photodynamic therapy and gene-silencing for precise cancer cell therapy

Nanoscale ◽  
2020 ◽  
Vol 12 (18) ◽  
pp. 10380-10389 ◽  
Author(s):  
Jin-Tao Yi ◽  
Qing-Shan Pan ◽  
Chang Liu ◽  
Yan-Lei Hu ◽  
Ting-Ting Chen ◽  
...  

An intelligent DNA-MnO2 nanodevice was designed for the telomerase-activated photodynamic (PDT) and gene-silencing synergistic effect for cancer cells theranostic.

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Khatereh Khorsandi ◽  
Reza Hosseinzadeh ◽  
Elham Chamani

Abstract Background Melanoma as a type of skin cancer, is associated with a high mortality rate. Therefore, early diagnosis and efficient surgical treatment of this disease is very important. Photodynamic therapy (PDT) involves the activation of a photosensitizer by light at specific wavelength that interacts with oxygen and creates singlet oxygen molecules or reactive oxygen species (ROS), which can lead to tumor cell death. Furthermore, one of the main approches in the prevention and treatment of various cancers is plant compounds application. Phenolic compounds are essential class of natural antioxidants, which play crucial biological roles such as anticancer effects. It was previously suggested that flavonoid such as rutoside could acts as pro-oxidant or antioxidant. Hence, in this study, we aimed to investigate the effect of rutoside on the combination therapy with methylene blue (MB) assisted by photodynamic treatment (PDT) using red light source (660 nm; power density: 30 mW/cm2) on A375 human melanoma cancer cells. Methods For this purpose, the A375 human melanoma cancer cell lines were treated by MB-PDT and rutoside. Clonogenic cell survival, MTT assay, and cell death mechanisms were also determined after performing the treatment. Subsequently, after the rutoside treatment and photodynamic therapy (PDT), cell cycle and intracellular reactive oxygen species (ROS) generation were measured. Results The obtained results showed that, MB-PDT and rutoside had better cytotoxic and antiprolifrative effects on A375 melanoma cancer cells compared to each free drug, whereas the cytotoxic effect on HDF human dermal fibroblast cell was not significant. MB-PDT and rutoside combination induced apoptosis and cell cycle arrest in the human melanoma cancer cell line. Intracellular ROS increased in A375 cancer cell line after the treatment with MB-PDT and rutoside. Conclusion The results suggest that, MB-PDT and rutoside could be considered as novel approaches as the combination treatment of melanoma cancer.


Drug Research ◽  
2018 ◽  
Vol 68 (06) ◽  
pp. 335-343 ◽  
Author(s):  
Raana Bagheri ◽  
Zohreh Sanaat ◽  
Nosratollah Zarghami

Abstract Background Telomerase is known as a global therapeutic target in cancer cells due to its main role in tumorigenesis. Nowadays, it is proposed new treatment methods based on molecular target therapy by bioactive substances such as curcumin and chrysin with fewer side effects than other chemical drugs. But due to their low aqueous solubility and high clearance in the bloodstream it can be used of nanoparticles to increase their half-life and biocompatibility of them. Therefore, the goal of this study was to evaluate the effect of Chrysin-Curcumin on the expression of telomerase gene in SW480 colorectal cancer cell line. Material and method PLGA-PEG nanoparticles synthesized and were confirmed using by the scanning electron microscope (SEM) and FTIR Spectroscopy. After treatment of SW480 cells by curcumin and chrysin loaded nanoparticles, their toxicity to cancer cells, was evaluated by MTT. Then, the inhibition of hTERT gene expression was measured using qRT-PCR method. Result The results of MTT test showed nanocapsulated curcumin and chrysin compared with free forms of these compounds have high synergistic effect on sw480 cells. Also, real time-PCR showed significant decrease in hTERT gene expression in SW480 cells that treated with nano-curcumin and nano-chrysin compare to untreated cells. Conclusion Nano-encapsulation of curcumin and chrysin enhanced delivery of these compounds to SW480 colorectal cancer cells and therefore it can be conclude that PLGA-PEG nanoparticles promote anticancer effects of curcumin-chrysin by increasing bioavailability and the solubility of these drugs.


2016 ◽  
Vol 4 (1) ◽  
pp. 169-176 ◽  
Author(s):  
Youyong Yuan ◽  
Shidang Xu ◽  
Chong-Jing Zhang ◽  
Ruoyu Zhang ◽  
Bin Liu

The currently available photosensitizers (PSs) for photodynamic therapy (PDT) can easily lead to undesirable normal cell death due to their intrinsic photo-toxicity and lack of selectivity for cancer cells.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Maria Mileo ◽  
Donato Di Venere ◽  
Stefania Mardente ◽  
Stefania Miccadei

Combined treatment of several natural polyphenols and chemotherapeutic agents is more effective comparing to the drug alone in inhibiting cancer cell growth. Polyphenolic artichoke extracts (AEs) have been shown to have anticancer properties by triggering apoptosis or reactive oxygen species- (ROS-) mediated senescence when used at high or low doses, respectively. Our aim was to explore the chemosensitizing potential of AEs in order to enhance the efficacy of conventional chemotherapy in breast cancer cells. We employed breast cancer cell lines to assess the potential synergistic effect of a combined treatment of AEs/paclitaxel (PTX) or AEs/adriamycin (ADR) and to determine the underlying mechanisms correlated to this potential therapeutic approach. Our data shows that AEs/PTX reduced cell proliferation by increasing DNA damage response (DDR) mediated by Flap endonuclease 1 (FEN1) downregulation that results into enhanced breast cancer cell sensitivity to chemotherapeutic drugs. We demonstrated that ROS/Nrf2 and p-ERK pathways are two molecular mechanisms involved in the synergistic effect of AEs plus PTX treatment. To highlight the role of ROS herein, we report that the addition of antioxidant N-acetylcysteine (NAC) significantly decreased the antiproliferative effect of the combined treatment. A combined therapy could be able to reduce the dose of chemotherapeutic drugs, minimizing toxicity and side effects. Our results suggest the use of artichoke polyphenols as ROS-mediated sensitizers of chemotherapy paving the way for innovative and promising natural compound-based therapeutic strategies in oncology.


Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 658 ◽  
Author(s):  
Rachel Riley ◽  
Rachel O’Sullivan ◽  
Andrea Potocny ◽  
Joel Rosenthal ◽  
Emily Day

Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT have been extensively evaluated as independent therapeutic strategies, they each face limitations that hinder their overall success. To overcome these limitations, we evaluated a dual PTT/PDT strategy for treatment of triple negative breast cancer (TNBC) cells mediated by a powerful combination of silica core/gold shell nanoshells (NSs) and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based (Pd[DMBil1]-PEG750) photosensitizers (PSs), which enable PTT and PDT, respectively. We found that dual therapy works synergistically to induce more cell death than either therapy alone. Further, we determined that low doses of light can be applied in this approach to primarily induce apoptotic cell death, which is vastly preferred over necrotic cell death. Together, our results show that dual PTT/PDT using silica core/gold shell NSs and Pd[DMBil1]-PEG750 PSs is a comprehensive therapeutic strategy to non-invasively induce apoptotic cancer cell death.


2021 ◽  
Vol 10 (4) ◽  
pp. 841 ◽  
Author(s):  
Hiromi Kataoka ◽  
Hirotada Nishie ◽  
Mamoru Tanaka ◽  
Makiko Sasaki ◽  
Akihiro Nomoto ◽  
...  

In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell selectivity and antitumor effects of TS PDT are not comprehensive. The Warburg effect describes the elevated rate of glycolysis in cancer cells, despite the presence of sufficient oxygen. Because cancer cells absorb considerable amounts of glucose, they are visible using positron emission tomography (PET). We developed a third-generation PDT based on the Warburg effect by synthesizing novel photosensitizers (PSs) in the form of sugar-conjugated chlorins. Glucose-conjugated (tetrafluorophenyl) chlorin (G-chlorin) PDT revealed significantly stronger antitumor effects than TS PDT and induced immunogenic cell death (ICD). ICD induced by PDT enhances cancer immunity, and a combination therapy of PDT and immune checkpoint blockers is expected to synergize antitumor effects. Mannose-conjugated (tetrafluorophenyl) chlorin (M-chlorin) PDT, which targets cancer cells and tumor-associated macrophages (TAMs), also shows strong antitumor effects. Finally, we synthesized a glucose-conjugated chlorin e6 (SC-N003HP) that showed 10,000–50,000 times stronger antitumor effects than TS (IC50) in vitro, and it was rapidly metabolized and excreted. In this review, we discuss the potential and the future of next-generation cancer cell-selective PDT and describe three types of sugar-conjugated PSs expected to be clinically developed in the future.


2015 ◽  
Author(s):  
◽  
Kaminee Maduray

Photodynamic therapy (PDT) is emerging as a viable alternative to invasive anti-cancer treatment regimens such as surgery, chemotherapy or radiotherapy. A series of metal – based phthalocyanine complexes have been discovered that may be used as a drug or photosensitizer in photodynamic therapy for the treatment of cancers. During photodynamic therapy the photosensitizer is administrated intravenously or topically to the patient before laser treatment at an appropriate wavelength is delivered to the cancerous site to activate the photosensitizer. The activated photosensitizer will react with oxygen typically present in the cancerous tissue to produce reactive oxygen species for the eradication of the cancerous tissue. This is the first study where gallium (GaPcCl), indium (InPcCl) and iron (FePcCl) Pc chloride complexes were used for photodynamic research. These metal – based phthalocyanine complexes were investigated using different cancer cell lines (Caco-2, MCF-7, melanoma and A549). Also, the baseline cellular uptake and photodynamic effect of these complexes were established on healthy normal cells (human fibroblast cells). Fluorescent spectrophotometry showed that all three photosensitizers accumulated in a time-dependent manner in Caco-2, MCF-7, melanoma and A549 cancer cells, as well as in healthy normal fibroblast cell in amounts which increased over a period of 24 hours, with emission peaking at 24 hours for all cell lines. Dark toxicity effects and photodynamic therapy efficacy were established with a MTT assay. High concentrations of inactive GaPcCl, InPcCl and FePcCl was toxic to Caco-2, melanoma, A549 and fibroblast cells. However, all three photosensitizers were in its inactive state at low and high photosensitizing concentrations were highly toxic to MCF-7 cancer cells. On the other hand, in vitro photodynamic therapy treatment with both low and high concentrations of GaPcCl, InPcCl and FePcCl were observed to be potently cytotoxic towards all four cancer cell lines upon exposure to laser light for 22 seconds (2.5 J/cm2), 39 seconds (4.5 J/cm2) and 74 seconds (8.5 J/cm2). These results revealed that all three photosensitizers reacts to photodynamic therapy in a concentration-dependent (photosensitizer) and dose-dependent (light dose/time) manner. At 24 hours after photodynamic therapy, the most effective treatment parameters were laser treatment for 74 seconds with FePcCl concentrations from 60 µg/ml - 100 µg/ml which resulted in 0% cell survival of Caco-2 cancer cells. A short laser treatment time of 74 seconds for activation of FePcCl (20 µg/ml) resulted in 0% cell survival of MCF-7 cancer cells. Similarly, FePcCl (40 µg/ml - 100 µg/ml) activated for 22 seconds, 39 seconds and 74 seconds resulted in 100% cell death of A549 cancer cells. Photodynamic therapy treatment with GaPcCl and InPcCl were very effective in reducing the cell viability of melanoma cancer cells. Healthy normal fibroblast cells survived in vitro photodynamic therapy treatment with all three photosensitizers much better than the cancer (Caco-2, MCF-7, melanoma and A549) cells. This confirms the previously reported results that photosensitizers such as phthalocyanines and its metal-based complexes preferentially accumulate in cancer cells than normal healthy cells. All three photosensitizers localized in mitochondria and lysosomes of the Caco-2, MCF-7 and A549 cancer cells. In melanoma cancer cells InPcCl also localized in the mitochondria and lysosome, but GaPcCl and FePcCl localized in mitochondria only. Apoptosis was identified via microscopical and flow cytometric investigations, as the dominant mode of cell death induced by GaPcCl, InPcCl and FePcCl mediated photodynamic therapy in cancer cell lines tested. Therefore, this study concludes that GaPcCl, InPcCl and FePcCl are effective photosensitizers for the in vitro PDT treatment of cancer cells. The effective in vitro PDT treatment for each cell line was dependent on the photosensitizer concentration and illumination period for each of the different photosensitizers.


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5990
Author(s):  
Yuan Xu ◽  
Yang Tan ◽  
Xiuqin Ma ◽  
Xiaoyi Jin ◽  
Ye Tian ◽  
...  

Photodynamic therapy (PDT) represents an effective treatment to cure cancer. The targeting ability of the photosensitizer is of utmost importance. Photosensitizers that discriminate cancer cells can avoid the killing of normal cells and improve PDT efficacy. However, the design and synthesis of photosensitizers conjugated with a recognition unit of cancer cell markers is complex and may not effectively target cancer. Considering that the total RNA content in cancer cells is commonly higher than in normal cells, this study has developed the photosensitizer QICY with RNA-targeting abilities for the discrimination of cancer cells. QICY was specifically located in cancer cells rather than normal cells due to their stronger electrostatic interactions with RNA, thereby further improving the PDT effects on the cancer cells. After intravenous injection into mice bearing a xenograft tumor, QICY accumulated into the tumor location through the enhanced permeability and retention effect, automatically targeted cancer cells under the control of RNA, and inhibited tumor growth under 630 nm laser irradiation without obvious side effects. This intelligent photosensitizer with RNA-targeting ability not only simplifies the design and synthesis of cancer-cell-targeting photosensitizers but also paves the way for the further development of highly efficient PDTs.


RSC Advances ◽  
2016 ◽  
Vol 6 (99) ◽  
pp. 96942-96945 ◽  
Author(s):  
Jun Ai ◽  
Jing Li ◽  
Lu Ga ◽  
Guohong Yun ◽  
Li Xu ◽  
...  

A new type of G-quadruplex/protoporphyrin IX-functionalized silver nanoconjugate was prepared and used for the targeted photodynamic therapy of cancer cells via the specific interaction between AS1411 and the nucleolin on the cell surface.


RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112393-112402 ◽  
Author(s):  
Wei Deng ◽  
Zofia Kautzka ◽  
Wenjie Chen ◽  
Ewa M Goldys

Enhanced 1O2 generation from PLGA loaded with verteporfin and gold nanoparticles under light illumination has the potential to improve cancer cell-killing effect.


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