scholarly journals Folate-Targeted Transgenic Activity of Dendrimer Functionalized Selenium Nanoparticles In Vitro

2020 ◽  
Vol 21 (19) ◽  
pp. 7177
Author(s):  
Nikita Simone Pillay ◽  
Aliscia Daniels ◽  
Moganavelli Singh

Current chemotherapeutic drugs, although effective, lack cell-specific targeting, instigate adverse side effects in healthy tissue, exhibit unfavourable bio-circulation and can generate drug-resistant cancers. The synergistic use of nanotechnology and gene therapy, using nanoparticles (NPs) for therapeutic gene delivery to cancer cells is hereby proposed. This includes the benefit of cell-specific targeting and exploitation of receptors overexpressed in specific cancer types. The aim of this study was to formulate dendrimer-functionalized selenium nanoparticles (PAMAM-SeNPs) containing the targeting moiety, folic acid (FA), for delivery of pCMV-Luc-DNA (pDNA) in vitro. These NPs and their gene-loaded nanocomplexes were physicochemically and morphologically characterized. Nucleic acid-binding, compaction and pDNA protection were assessed, followed by cell-based in vitro cytotoxicity, transgene expression and apoptotic assays. Nanocomplexes possessed favourable sizes (<150 nm) and ζ-potentials (>25 mV), crucial for cellular interaction, and protected the pDNA from degradation in an in vivo simulation. PAMAM-SeNP nanocomplexes exhibited higher cell viability (>85%) compared to selenium-free nanocomplexes (approximately 75%), confirming the important role of selenium in these nanocomplexes. FA-conjugated PAMAM-SeNPs displayed higher overall transgene expression (HeLa cells) compared to their non-targeting counterparts, suggesting enhanced receptor-mediated cellular uptake. Overall, our results bode well for the use of these nano-delivery vehicles in future in vivo studies.

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1269
Author(s):  
Razan J. Masad ◽  
Shoja M. Haneefa ◽  
Yassir A. Mohamed ◽  
Ashraf Al-Sbiei ◽  
Ghada Bashir ◽  
...  

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer.


2013 ◽  
Vol 27 (3) ◽  
pp. 203-207 ◽  
Author(s):  
Nasibeh Beheshti ◽  
Saied Soflaei ◽  
Mojtaba Shakibaie ◽  
Mohammad Hossein Yazdi ◽  
Fatemeh Ghaffarifar ◽  
...  

2010 ◽  
Vol 1257 ◽  
Author(s):  
Andrea Fornara ◽  
Alberto Recalenda ◽  
Jian Qin ◽  
Abhilash Sugunan ◽  
Fei Ye ◽  
...  

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 205-205
Author(s):  
Thomas Nelius ◽  
Courtney Jarvis ◽  
Dalia Martinez-Marin ◽  
Stephanie Filleur

205 Background: Docetaxel/DTX and cabazitaxel/CBZ have shown promise in the treatment of metastatic Castration-Refractory Prostate Cancer/mCPRC however, comparative studies are missing. Toxicities of these drugs are significant, urging the need to modify taxane regimens. Recently, low-dose metronomic/LDM treatments using conventional chemotherapeutic drugs have shown benefits in CPRC in improving the effect of anti-angiogenic agents. Previously, we have demonstrated that LDM-DTX in combination with PEDF curbs significantly CRPC growth, limits metastases formation and prolongs survival in vivo. In this study, we intended to compare the cytotoxic effect of CBZ and DTX on CRPC cells in vitro and CL1 tumors in vivo. Methods: PC3, DU145 cell lines were from ATCC.CL1 cells were obtained from androgen-deprived LNCaP cells. Cell proliferation was assessed by crystal violet staining and cell cycle analyses. In vitro cytotoxicity assays were performed on CL1 cells/RAW264.7 macrophages co-cultures treated with PEDF and increasing doses of taxanes. For the in vivo studies, CL1 cells were engineered to stably express the DsRed Express protein +/- PEDF. PEDF anti-tumor effects were assessed on s.c. xenografts treated with DTX (5mg/kg ip ev. 4 day) as reference, CBZ (5mg/kg ip ev. 4 days, 1mg/kg for 10 days, 0.5mg/kg q.a.d. and 0.1mg/kg daily) or placebo. Results: CBZ limits cell proliferation with a greater efficacy than DTX in all CRPC cell lines tested. DU145 presented the largest difference. High doses of taxane blocked tumor cells in mitosis, whereas LDM increased the SubG1 population. This effect was significantly higher in DU145 cells treated with CBZ. In vivo, 5mg/kg CBZ delayed tumor growth more efficiently than 5mg/kg DTX. PEDF/5mg/kg CBZ markedly delayed tumor growth compared to all treatments. Finally, engulfment of tumor cells by macrophages was higher in combined treatments suggesting an inflammation-related process. Conclusions: CBZ is more efficient than DTX both in vitro and in vivo.The data also reinforce PEDF as a promising anti-neoplasic agent in combination with LDM taxane chemotherapies.


2013 ◽  
Vol 63 (4) ◽  
pp. 479-491 ◽  
Author(s):  
Bhavesh P. Depani ◽  
Anuja A. Naik ◽  
Hema A. Nair

Abstract Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.


Author(s):  
Mahdi Hatamipour ◽  
Mahmoud R. Jaafari ◽  
Mahtab Zangui ◽  
Neda Shakour ◽  
Amirhossein Sahebkar

Background: Pyrvinium pamoate (PP) is an old drug approved by the FDA for the treatment of pinworm infections. Recently, PP has been introduced as an antitumor agent. However, low aqueous solubility severely limits its potential effects. In this study, we developed a liposomal formulation of pyrvinium pamoate to investigate its in vitro cytotoxicity and in vivo efficacy against melanoma cells. Materials & Methods: As drug carriers, liposomes were fabricated using thin-film method. PP was encapsulated within liposomes using remote loading method. We evaluated morphology, particle size, and Zeta potential of the liposomes. Additionally, high-performance liquid chromatography (HPLC) was employed for qualitative and quantitative analysis. Then we investigated our liposomal PP for its in vitro cytotoxicity as well as the tumor growth inhibition in C57BL/6 mice bearing B16F0 melanoma tumors. Results: Based on the analytical result, the liposomal drug delivery system is a homogeneous and stable colloidal suspension of PP particles. Images of Atomic force microscopy and particle size data showed that all the prepared nanocarrier were spherical with a diameter of approximately 101 nm. According to both in vitro and in vivo studies, nanoliposomal PP exhibited an improved anti-proliferative potential against B16F10 melanoma tumor compared with free PP. Conclusion: Liposomal encapsulation improves water solubility of PP and enhances its anti-cancer activity.


2021 ◽  
Vol 11 (11) ◽  
pp. 4897
Author(s):  
Bárbara Socas-Rodríguez ◽  
M. Vanessa Torres-Cornejo ◽  
Gerardo Álvarez-Rivera ◽  
Jose A. Mendiola

In this work, a review about the applicability of eutectic solvents, mainly deep eutectic solvents (DES) and natural deep eutectic solvents (NADES), for the extraction of bioactive compounds from natural products has been carried out. These alternative solvents have shown not only to have high extraction yields but also to be environmentally friendly, exhibiting very low or almost no toxicity, compared to conventional organic solvents. The last trends and main extraction methods that have been most widely used in studies using these emerging solvents have been reviewed, as well as the varied natural sources in which they have been used, including agro-food by-products. Besides the toxicity, biodegradability of these solvents is reviewed. Likewise, different reported bioactivity tests have been included, in which extracts obtained with these ecological solvents have been tested from antioxidant activity analysis to in vivo studies with rats, through in vitro cytotoxicity tests.


Nanomaterials ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2658
Author(s):  
Rúben G. R. Pinheiro ◽  
Marina Pinheiro ◽  
Ana Rute Neves

Quercetin is a flavonol present in many vegetables and fruits. Generally, quercetin can be found in aglycone and glycoside forms, mainly in leaves. The absorption of this compound occurs in the large and small intestine, where it suffers glucuronidation, sulfidation, and methylation to improve hydrophilicity. After metabolization, which occurs mainly in the gut, it is distributed throughout the whole organism and is excreted by feces, urine, and exhalation of carbon dioxide. Despite its in vitro cytotoxicity effects, in vivo studies with animal models ensure its safety. This compound can protect against cancer, cardiovascular diseases, chronic inflammation, oxidative stress, and neurodegenerative diseases due to its radical scavenging and anti-inflammatory properties. However, its poor bioavailability dampens the potential beneficial effects of this flavonoid. In that sense, many types of nanocarriers have been developed to improve quercetin solubility, as well as to design tissue-specific delivery systems. All these studies manage to improve the bioavailability of quercetin, allowing it to increase its concentration in the desired places. Collectively, quercetin can become a promising compound if nanotechnology is employed as a tool to enhance its therapeutic efficacy.


2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Gerhard Schmalz ◽  
Simin Li ◽  
Ralph Burkhardt ◽  
Sven Rinke ◽  
Felix Krause ◽  
...  

The aim of this review is to discuss current findings regarding the roles of miRNAs in periodontal diseases and the potential use of saliva as a diagnostic medium for corresponding miRNA investigations. For periodontal disease, investigations have been restricted to tissue samples and five miRNAs, that is, miR-142-3p, miR-146a, miR-155, miR-203, and miR-223, were repeatedly validated in vivo and in vitro by different validation methods. Particularly noticeable are the small sample sizes, different internal controls, and different case definitions of periodontitis in in vivo studies. Beside of that, the validated miRNAs are associated with inflammation and therefore with various diseases. Furthermore, several studies successfully explored the use of salivary miRNA species for the diagnosis of oral cancer. Different cancer types were investigated and heterogeneous methodology was used; moreover, no overlap of results was found. In conclusion, five miRNAs have consistently been reported for periodontitis; however, their disease specificity, detectability, and expression in saliva and their importance as noninvasive markers are questionable. In principle, a salivary miRNA diagnostic method seems feasible. However, standardized criteria and protocols for preanalytics, measurements, and analysis should be established to obtain comparable results across different studies.


Planta Medica ◽  
2020 ◽  
Vol 86 (06) ◽  
pp. 415-424
Author(s):  
Júlia Martins ◽  
Joana Coelho ◽  
Maraine Catarina Tadini ◽  
Rebeca Oliveira de Souza ◽  
Sonia Aparecida Figueiredo ◽  
...  

Abstract Ocotea fasciculata presents yangambin (YAN) and its isomer epi-yangambin (EPI-YAN) as major lignans, which are employed as the plant markers for quality control purposes and as potential pharmacological compounds. However, a gap between the pure isomers and safety and efficacy protocols is faced by the scientific community. In this context, this work aimed to report (i) a new and advantageous purifying process in a semi-preparative scale for YAN and EPI-YAN isolation from Ocotea fasciculata, and (ii) an in vitro cytotoxicity study to estimate, for the first time, the LD50 values of the isolated epimers, as well as the influence of albumin concentration in cell culture medium. The best condition for epimers isolation was achieved in normal-phase liquid chromatography. The lignan fraction (LF), previously obtained from the plant ethanolic extract, was purified yielding 17% and 29% of YAN and EPI-YAN, respectively. The in vitro study demonstrated that YAN and EPI-YAN were safe, and only at the highest concentration studied, a decrease on cell viability was observed. The estimated LD50 value was higher than 1612 mg/kg for both epimers. The LF, on the other hand, demonstrated an estimated LD50 of 422 mg/kg. Lignan cytotoxicity studies also evidenced that the higher cell viability was related to the higher concentration of fetal bovine serum as a source of albumin in medium. This is the first time the LD50 and safety of the isolated epimers were estimated, opening up great perspectives of success in in vivo studies.


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