scholarly journals Enhanced Photodynamic Anticancer Activities of Multifunctional Magnetic Nanoparticles (Fe3O4) Conjugated with Chlorin e6 and Folic Acid in Prostate and Breast Cancer Cells

Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 722 ◽  
Author(s):  
Kyong-Hoon Choi ◽  
Ki Nam ◽  
Guangsup Cho ◽  
Jin-Seung Jung ◽  
Bong Park

Photodynamic therapy (PDT) is a promising alternative to conventional cancer treatment methods. Nonetheless, improvement of in vivo light penetration and cancer cell-targeting efficiency remain major challenges in clinical photodynamic therapy. This study aimed to develop multifunctional magnetic nanoparticles conjugated with a photosensitizer (PS) and cancer-targeting molecules via a simple surface modification process for PDT. To selectively target cancer cells and PDT functionality, core magnetic (Fe3O4) nanoparticles were covalently bound with chlorin e6 (Ce6) as a PS and folic acid (FA). When irradiated with a 660-nm long-wavelength light source, the Fe3O4-Ce6-FA nanoparticles with good biocompatibility exerted marked anticancer effects via apoptosis, as confirmed by analyzing the translocation of the plasma membrane, nuclear fragmentation, activities of caspase-3/7 in prostate (PC-3) and breast (MCF-7) cancer cells. Ce6, used herein as a PS, is thus more useful for PDT because of its ability to produce a high singlet oxygen quantum yield, which is owed to deep penetration by virtue of its long-wavelength absorption band; however, further in vivo studies are required to verify its biological effects for clinical applications.

2021 ◽  
Vol 17 (2) ◽  
pp. 205-215
Author(s):  
Zhenbo Sun ◽  
Mingfang Luo ◽  
Jia Li ◽  
Ailing Wang ◽  
Xucheng Sun ◽  
...  

Imaging-guided cancer theranostic is a promising strategy for cancer diagnostic and therapeutic. Photodynamic therapy (PDT), as an approved treatment modality, is limited by the poor solubility and dispersion of photosensitizers (PS) in biological fluids. Herein, it is demonstrated that superparamagnetic iron oxide (SPIO)-based nanoparticles (SCFs), prepared by conjugated with Chlorin e6 (Ce6) and modified with folic acid (FA) on the surface, can be used as versatile drug delivery vehicles for effective PDT. The nanoparticles are great carriers for photosensitizer Ce6 with an extremely high loading efficiency. In vitro fluorescence imaging and in vivo magnetic resonance imaging (MRI) results indicated that SCFs selectively accumulated in tumor cells. Under near-infrared laser irradiation, SCFs were confirmed to be capable of inducing low cell viability of RM-1 cells In vitro and displaying efficient tumor ablation with negligible side effects in tumor-bearing mice models.


2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.


2005 ◽  
pp. 215
Author(s):  
V. A. Marquez-Lemus ◽  
B. M. Noguez-Juarez ◽  
L. Solano-Rodriguez ◽  
A. J. Perez-Zapata ◽  
O. P. Schneider-Ehrenberg ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1547
Author(s):  
Pablo Lara ◽  
Ruben V. Huis in ‘t Veld ◽  
Carla Jorquera-Cordero ◽  
Alan B. Chan ◽  
Ferry Ossendorp ◽  
...  

Photodynamic therapy (PDT) is a promising and clinically approved method for the treatment of cancer. However, the efficacy of PDT is often limited by the poor selectivity and distribution of the photosensitizers (PS) toward the malignant tumors, resulting in prolonged periods of skin photosensitivity. In this work, we present a simple and straightforward strategy to increase the tumor distribution, selectivity, and efficacy of lipophilic PS zinc phthalocyanine (ZnPc) in colon cancer by their stabilization in purified, naturally secreted extracellular vesicles (EVs). The PS ZnPc was incorporated in EVs (EV-ZnPc) by a direct incubation strategy that did not affect size distribution or surface charge. By using co-culture models simulating a tumor microenvironment, we determined the preferential uptake of EV-ZnPc toward colon cancer cells when compared with macrophages and dendritic cells. We observed that PDT promoted total tumor cell death in normal and immune cells, but showed selectivity against cancer cells in co-culture models. In vivo assays showed that after a single intravenous or intratumoral injection, EV-ZnPc were able to target the tumor cells and strongly reduce tumor growth over 15 days. These data expose opportunities to enhance the potential and efficacy of PDT using simple non-synthetic strategies that might facilitate translation into clinical practice.


Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1064
Author(s):  
Pablo Betancourt ◽  
Nadia Brocal ◽  
Eulàlia Sans-Serramitjana ◽  
Carlos Zaror

The eradication of endodontic pathogens continues to be the focus of the search for new root canal system (RCS) disinfection strategies. This scoping review provides a comprehensive synthesis of antimicrobial photodynamic therapy (aPDT) using nanoparticles (NPs) as an alternative to optimize RCS disinfection. A systematic search up to March 2021 was carried out using the MEDLINE, EMBASE, Scopus, Lilacs, Central Cochrane Library, and BBO databases. We included studies focused on evaluating the activation of NPs by aPDT in inoculated root canals of human or animal teeth or bacterial cultures in the laboratory. The selection process and data extraction were carried out by two researchers independently. A qualitative synthesis of the results was performed. A total of seventeen studies were included, of which twelve showed a substantial antibacterial efficacy, two assessed the substantivity of the disinfection effect, and three showed low cytotoxicity. No adverse effects were reported. The use of functionalized NPs with photosensitizer molecules in aPDT has been shown to be effective in reducing the bacteria count, making it a promising alternative in endodontic disinfection. Further studies are needed to assess the development of this therapy in in vivo conditions, with detailed information about the laser parameters used to allow the development of safe and standardized protocols.


2019 ◽  
Vol 12 (3) ◽  
pp. 140 ◽  
Author(s):  
Karem Janeth Rimachi Hidalgo ◽  
Juliana Cabrini Carmello ◽  
Cláudia Carolina Jordão ◽  
Paula Aboud Barbugli ◽  
Carlos Alberto de Sousa Costa ◽  
...  

Background: It has been demonstrated that azole-resistant strains of Candida albicans have a greater resistance to antimicrobial photodynamic therapy (aPDT) when compared to their more susceptible counterparts. For this reason, the present study evaluated the efficacy of aPDT, together with nystatin (NYS), in the treatment of oral candidiasis in vivo. Methods: Mice were infected with fluconazole-resistant C. albicans (ATCC 96901). To perform the combined therapy, aPDT, mediated by Photodithazine (PDZ) and LED light, was used together with NYS. The efficacy of the treatments was evaluated by microbiological, macroscopic, histopathological and Confocal Scanning Laser Microscopy analyses of the lesions. The expression of p21 and p53, proteins associated with cell death, from the tongues of mice, was also performed. Results: The combined therapy reduced the fungal viability by around 2.6 log10 and decreased the oral lesions and the inflammatory reaction. Additionally, it stimulated the production of p53 and p21. Conclusions: The combined therapy is a promising alternative treatment for oral candidiasis induced by C. albicans resistant to fluconazole.


2019 ◽  
Vol 20 (3) ◽  
pp. 697 ◽  
Author(s):  
Shaoming Jin ◽  
Zhongyao Du ◽  
Huiyuan Guo ◽  
Hao Zhang ◽  
Fazheng Ren ◽  
...  

The glucose analog, 2-deoxyglucose (2-DG), specifically inhibits glycolysis of cancer cells and interferes with the growth of cancer cells. However, the excellent water solubility of 2-DG makes it difficult to be concentrated in tumor cells. In this study, a targeted nano-pharmacosome was developed with folic acid-modified 2-DG (FA-2-DG) by using amino ethanol as a cleavable linker. FA-2-DG was able to self-assemble, forming nano-particles with diameters of 10–30 nm. The biological effects were evaluated with cell viability assays and flow cytometry analysis. Compared with a physical mixture of folic acid and 2-DG, FA-2-DG clearly reduced cell viability and resulted in cell cycle arrest. A computational study involving docking simulation suggested that FA-2-DG can dock into the same receptor as folic acid, thus confirming that the structural modification did not affect the targeting performance. The results indicated that the nano-pharmacosome consisting of FA-2-DG can be used for targeting in a nano-drug delivery system.


2020 ◽  
Vol 21 (13) ◽  
pp. 4745 ◽  
Author(s):  
Prabhavathi Sundaram ◽  
Heidi Abrahamse

Colon cancer is the third major cancer contributor to mortality worldwide. Nanosized particles have attracted attention due to their possible contribution towards cancer treatment and diagnosis. Photodynamic therapy (PDT) is a cancer therapeutic modality that involves a light source, a photosensitizer and reactive oxygen species. Carbon nanotubes are fascinating nanocarriers for drug delivery, cancer diagnosis and numerous potential applications due to their unique physicochemical properties. In this study, single walled carbon nanotubes (SWCNTs) were coupled with hyaluronic acid (HA) and chlorin e6 (Ce6) coated on the walls of SWCNTs. The newly synthesized nanobiocomposite was characterized using ultraviolet-visible spectroscopy, Fourier transform electron microscopy (FTIR), X-ray diffraction analysis (XRD), particle size analysis and zeta potential. The loading efficiency of the SWCNTs-HA for Ce6 was calculated. The toxicity of the nanobiocomposite was tested on colon cancer cells using PDT at a fluence of 5 J/cm2 and 10 J/cm2. After 24 h, cellular changes were observed via microscopy, LDH cytotoxicity assay and cell death induction using annexin propidium iodide. The results showed that the newly synthesized nanobiocomposite enhanced the ability of PDT to be a photosensitizer carrier and induced cell death in colon cancer cells.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chengjuan Zhang ◽  
Junxia Zhang ◽  
Qiong Wu ◽  
Benling Xu ◽  
Guoguo Jin ◽  
...  

Abstract Background As a novel type of isothiocyanate derived from radish seeds from cruciferous vegetables, sulforaphene (SFE, 4-methylsufinyl-3-butenyl isothiocyanate) has various important biological effects, such as anti-oxidative and anti-bacterial effects. Recently, sulforaphene has attracted increasing attention for its anti-tumor effects and its ability to suppress the development of multiple tumors through different regulatory mechanisms. However, it has not yet been widely investigated for the treatment of esophageal cancer. Methods We observed an increased apoptosis in esophageal cancer cells on sulforaphene treatment through flow cytometry (FCM) analysis and transmission electron microscopy (TEM). Through mass spectrometry (MS) analysis, we further detected global changes in the proteomes and phosphoproteomes of esophageal cancer cells on sulforaphene treatment. The molecular mechanism of sulforaphene was verified by western blot,the effect and mechanism of SFE on esophageal cancer was further verified by patient-derived xenograft mouse model. Results We identified multiple cellular processes that were changed after sulforaphene treatment by proteomics. We found that sulforaphene could repress the phosphorylation of CREB through MSK2, leading to suppression of Bcl-2 and further promoted cell apoptosis. Additionally, we confirmed that sulforaphene induces tumor cell apoptosis in mice. Interestingly, we also observed the obvious inhibition of cell migration and invasion caused by sulforaphene treatment by inhibiting the expression of cadherin, indicating the complex effects of sulforaphene on the development of esophageal cancer. Conclusions Our data demonstrated that sulforaphene induced cell apoptosis and inhibits the invasion of esophageal cancer through a mechanism involving the inhibition of the MSK2–CREB–Bcl2 and cadherin pathway. Sulforaphene could therefore serve as a promising anti-tumor drug for the treatment of esophageal cancer.


2016 ◽  
Vol 31 (7) ◽  
pp. 1010-1025 ◽  
Author(s):  
Xiali Zhu ◽  
Heqing Huang ◽  
Yingjie Zhang ◽  
Huijuan Zhang ◽  
Lin Hou ◽  
...  

Safe and efficient drug delivery in a controllable fashion, especially remote and repeatable switch of on-demand drug release, is the subject of widespread attention. A kind of magnetic nanoparticles (DOX-Cit/CuS@Fe3O4-NPs) simultaneously consisted of Cit/CuS@Fe3O4 and doxorubicin (DOX) was presented. The drug release from DOX-Cit/CuS@Fe3O4-NPs could be successfully triggered by the presence of gelatinase, showing great promise for tumor-targeted drug release through an enzymatic degradation mechanism. Compared with free DOX, DOX-Cit/CuS@Fe3O4-NPs could not only specially deliver Cit/CuS@Fe3O4 and DOX into MCF-7 cells, but also could greatly improve the quantity of ROS produced in MCF-7 cells under of 980 nm laser irradiation. DOX-Cit/CuS@Fe3O4-NPs also had highly selective accumulation at tumor tissue of S180 tumor-bearing mice, which were along with a magnet near the tumor site. Furthermore, when combined with NIR laser irridation, DOX-Cit/CuS@Fe3O4-NPs showed a higher antitumor efficacy than the individual therapies in vitro and in vivo. This study showed that DOX-Cit/CuS@Fe3O4-NPs could be used as a platform for tumor chemotherapy, photothermal and photodynamic therapy.


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