Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

Tawfik, Essam A.; Ahamed, Maqusood; Almalik, Abdulaziz; Alfaqeeh, Mohammad; Alshamsan, Aws

doi:10.1016/j.jsps.2016.05.010

Cited by 43 publications

(39 citation statements)

References 28 publications

(26 reference statements)

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“…As it is seen, 5-fluorouracil has very small cytotoxic effect on HT-29 cells after 24-h of incubation, which was also confirmed in different publications. The highest cytotoxic effect on HT-29 cells starts after 5 days of incubation [92,93]. Also 24 h of incubation A549 cells with etoposide provides average cytotoxic effect, which increases with time of incubation.…”

Section: Discussionmentioning

confidence: 98%

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

et al. 2019

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A series of nine tetrahydroacridine derivatives with iodobenzoic moiety were synthesized and evaluated for their cytotoxic activity against cancer cell lines-A549 (human lung adenocarcinoma), HT-29 (human colorectal adenocarcinoma) and somatic cell line-EA.hy926 (human umbilical vein cell line). All compounds displayed high cytotoxicity activity against A549 (IC 50 59.12-14.87 µM) and HT-29 (IC 50 17.32-5.90 µM) cell lines, higher than control agents-etoposide and 5-fluorouracil. Structure-activity relationship showed that the position of iodine in the substituent in the para position and longer linker most strongly enhanced the cytotoxic effect. Among derivatives, 1i turned out to be the most cytotoxic and displayed IC 50 values of 14.87 µM against A549 and 5.90 µM against HT-29 cell lines. In hyaluronidase inhibition assay, all compounds presented anti-inflammatory activity, however, slightly lower than reference compound. ADMET prediction showed that almost all compounds had good pharmacokinetic profiles. 1b, 1c and 1f compounds turned out to act against chemoresistance in cisplatin-resistant 253J B-V cells. Compounds intercalated into DNA and inhibited cell cycle in G0/G1 phase-the strongest inhibition was observed for 1i in A549 and 1c in HT-29. Among compounds, the highest apoptotic effect in both cell lines was observed after treatment with 1i. Compounds caused DNA damage and H2AX phosphorylation, which was detected in A549 and HT-29 cells. All research confirmed anticancer properties of novel tetrahydroacridine derivatives and explained a few pathways of their mechanism of cytotoxic action.

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Section: Discussionmentioning

confidence: 98%

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

et al. 2019

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“…To improve the efficacy of chemotherapeutic drugs in cancer treatment, employing NPs with targeted delivery property were a promising method [21]. The activity of 5-FU is time-dependent, and the prolonged effect produced by PLGA NPs may contribute to the significant enhancement of the anticancer activity of 5-FU at least to a certain extent [22]. EGF was a commonly used binding agent for EGF receptor-overexpressing solid tumors including colon cancer [23].…”

Section: Discussionmentioning

confidence: 99%

Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perﬂuorocarbon

Wu¹,

Zhou²,

Zhu³

et al. 2019

Preprint

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Background: Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, poly lactic-co-glycolic acid (PLGA) has been shown to have potential as a broad therapeutic drug delivery system. This study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. Methods: We developed epidermal growth factor (EGF) functionalized poly PLGA nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perﬂuorocarbon (PFC) (EGF-PLGA@5Fu/PFC NPs) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated by morphology, size distribution, in vitro stability and release profile. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Results: We found that EGF-PLGA@5Fu/PFC NPs had an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. Targeted EGF-PLGA@5Fu/PFC NPs exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 colon cancer cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC relieved tumor hypoxia via transporting oxygen to the tumor. Conclusions: We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles might provide new potential for selective delivery of chemotherapy drugs to cancers.

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“…The mobile phase was consisted of 75:25 (v/v) of acetonitrile and Milli Q water and the pH of water was adjusted to 3 by orthophosphoric acid. The detection wavelength was set at 215 nm, the flow rate of the mobile phase was 1 mL/min and column temperature was set to 60 °C 36,57 . The drug concentration was calculated by using straight line equation: y = 16.784x+ 13529; R 2 = 0.9993.…”

Section: Drug Encapsulation Efficiencymentioning

confidence: 99%

“…At 3,6,12,24,48,72,96,120,144,168,192,240,264, 288 h after starting incubation, tubes were taken out from the water bath in triplicate and centrifuged at 11,000 rpm for 30 minutes. Thereafter, the supernatant was taken and 30 µL of it was injected in to the HPLC system for the determination of TAC concentration 36,57 .…”

Section: Drug Encapsulation Efficiencymentioning

confidence: 99%

“…Furthermore, PLGA NPs have also been shown to deliver antigens to dendritic cells 33 . So far, the extensive research on the application of PLGA as drug delivery system have resulted in several marketed formulations (injectable implants) for human use 34,35 .We have previously shown that PLGA NPs are capable of loading different types of payloads including small molecular weight drugs [36][37][38] , large molecular weight molecules 39,40 , as well as siRNA 41 . The drug-loaded PLGA NPs always exhibited diameters in the nano range, high loading efficiency, and sustained release of the payload in vitro.…”

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confidence: 99%

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Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity

Alshamsan

Binkhathlan

Kalam

et al. 2020

Sci Rep

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the aim of this study was to assess the ability of pLGA nanoparticles (nps) to reduce the tacrolimus (tAc)-associated nephrotoxicity following multiple dose administration. the mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro release profile of TAC-loaded NPs showed a sustained release of the drug with only less than 30% release within 12 days. Flow cytometry as well as fluorescence microscopy results confirmed the uptake of FITClabelled pLGA nps by dendritic cells. the ex vivo study showed that TAC-loaded NPs caused a significant suppression of the proliferation of CD4 + and CD8 + cells, which was comparable to the control formulation (prograf). In vivo immunosuppressive activity as well as the kidney function were assessed following drug administration to mice. The animals received TAC subcutaneously at a daily dose of 1 mg/kg for 30 days delivered as the control formulation (Prograf) or TAC-loaded NPs. The results revealed significantly lower drug-associated toxicity with an activity comparable to prograf for tAc-loaded pLGA nps. these findings show a potential for PLGA NPs in reducing the nephrotoxicity of TAC while preserving the immunosuppressive activity.Tacrolimus is a potent immunosuppressive agent used clinically to reduce the risk of graft rejection in post-operative transplants patients 1-3 . It acts by suppressing interleukin-2 (IL-2) production in T-cells 4 , and also by inhibiting phosphatase activity of calcineurin through binding to the intracellular immunophilin FKBP-12 5 . The currently available intravenous formulation of TAC (Prograf) contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions 6-8 . TAC is available in oral dosage forms including immediate release capsules (Prograf), extended release capsules (Astagraf XL and Advagraf), and extended release tablets (Envarsus XR). Several adverse effects have been reported with the use of TAC including hypertension, pruritus, leucocytosis, neurotoxicity, nephrotoxicity, cardiotoxicity and hepatotoxicity [9][10][11][12][13] . open Scientific RepoRtS | (2020) 10:6675 | https://doi.org/10.1038/s41598-020-63767-1 www.nature.com/scientificreports www.nature.com/scientificreports/ Drug-induced nephrotoxicity is the major dose-limiting side effect of TAC with a reported overall incidence as high as 44% 14 . Unfortunately, nephrotoxicity can lead to severe complications such as negative impact on graft survival and life expectancy of the patients. Indeed, nephrotoxic effects present challenges during therapeutic regimen with these drugs 15,16 . Several strategies have been proposed to address this problem. Dose reduction is one of the strategies that has been evaluated by clinicians along with using other agents such as sirolomus or everolimus, which are found to be effective in improving long-term effects in renal transplant cases 17,18 .Several formulations have been investigated to improve the aqueous ...

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Prolonged exposure of colon cancer cells to 5-fluorouracil nanoparticles improves its anticancer activity

Cited by 43 publications

References 28 publications

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

Novel tetrahydroacridine derivatives with iodobenzoic moieties induce G0/G1 cell cycle arrest and apoptosis in A549 non-small lung cancer and HT-29 colorectal cancer cells

Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perﬂuorocarbon

Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity

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