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@#In this study, the conjugate of eicosapentaenoic acid (EPA) and hyaluronic acid (HA) was synthesized and the anti-hepatoma activities in vitro were evaluated.The hyaluronic acid-eicosapentaenoic acid (HA-EPA)nanoparticle was synthesized by linking eicosapentaenoic acid with hyaluronic acid with cystamine.The structure of HA-EPA was characterized by nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FT-IR).Laser particle sizer and Zeta potential analyzer were used to detect the size and potential of HA-EPA.MTT assay was used to detect the anti-proliferative effect of HA-EPA on HepG2, Huh-7 and LX-2 cells in vitro.The effects of HA-EPA nanoparticles on the proliferation and apoptosis of HepG2 cells in vitro were investigated by EdU staining and TUNEL staining. The apoptosis was further confirmed by flow cytometry.The effect of HA-EPA nanoparticles on the migration and invasion of HepG2 cells was demonstrated by transwell and invasion experiments.The results of 1H NMR showed that HA-EPA was successfully synthesized, and the grafting rate of EPA on HA was (40 ± 5) %. The structure of HA-EPA was further confirmed by FT-IR.The particle size was (162.5 ± 10.2) nm, and the potential was -(4.47 ± 0.31) mV.MTT results showed that, with the prolongation of drug treatment time, HA-EPA showed a better inhibitory effect on the activity of HepG2 and Huh-7 cells than EPA under the same EPA content.After treated for 48 hours, the toxicity of HA-EPA to LX-2 cells was less than that of EPA.The results of 24-hour proliferation, apoptosis, migration and invasion of HepG2 showed that, the graft of hyaluronic acid improved the ability of EPA to inhibit proliferation, promote apoptosis, migration and invasion of HepG2 cells (P < 0.001), indicating that grafting of HA can significantly enhance the inhibitory effect of EPA on liver cancer with some role in reducing toxicity.
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OBJECTIVE To prep are folate-targeted miR- 221 antisense oligonucleotide （anti-miR-221）delivery system ，and to preliminarily evaluate its in vitro anti-cancer effect on hepatocellular carcinoma. METHODS Folate-targeted anti-miR- 221 liposomes（FRL）were prepared by thin-film dispersion method ；the particle size ，Zeta potential and encapsulation efficiency were determined. The delivery efficiency of folate-targeted anionic liposome in human hepatoma HepG 2 cells was determined by in vitro cellular uptake experiment using calcein as the model drug. Flow cytometry was used to detect the effects of FRL on the apoptosis and cell cycle of HepG 2 cells. RESULTS The particle size of prepared FRL was （172.70±3.76）nm，Zeta potential was （－1.16± 0.15）mV and encapsulation efficiency was （83.53±1.85）％. In vitro cellular uptake experiments showed that folate-targeted anionic liposome successfully delivered calcein to HepG 2 cells，and the delivery efficiency in targeted group was higher than that of non-targeted liposome group （P＜0.01）. Apoptosis experiment results showed that the apoptotic rate of HepG 2 cells treated with FRL was significantly higher than that of non-targeted liposome （P＜0.01）. In cell cycle experiment ，FRL could shorten the S phase fraction of HepG 2 cells and induced arrest in the G 0/G1 and G 2/M phases. CONCLUSIONS FRL can encapsulate anti-miR-221 well and deliver it to hepatocellular carcinoma HepG 2 cells successfully ，and has a good in vitro anti-hepatoma effect in inducing apoptosis and cell cycle regulation.
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@#The aim of this study was to study the synthesis of two folate conjugates and their application in the preparation of folate targeted liposome, and to investigate their targeting effect in hepatocellular carcinoma HepG2 cell line in vitro. In this study, Folate-PEG-Cholesteryl hemisuccinate(Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS)were synthesized by linking folate and cholesterol succinate with two kinds of PEG materials. Structures of Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS were characterized by 1H NMR and ultra-high resolution mass spectrometry. Calcein was selected as the model drug, and calcein liposomes FA-PEG2000-L and FA-PEG4000-L were prepared by film dispersion method using Folate-PEG2000-CHEMS and Folate-PEG4000-CHEMS, respectively. The particle size and Zeta potential of FA-PEG2000-L and FA-PEG4000-L were measured by laser particle size analyzer. The drug delivery effect of FA-PEG2000-L and FA-PEG4000-L was evaluated by cellular uptake experiment in HepG2 cell line in vitro. Flow cytometry and laser confocal scanning microscope were used to determine fluorescence in HepG2 cells in vitro. The results showed that the average particle size of calcein liposome was (205.8 ± 10.2) nm, and the Zeta potential of calcein liposome was -(1.19 ± 0.31) mV.There was no significant difference in particle size and Zeta potential between FA-PEG2000-L and FA-PEG4000-L. The fluorescence intensity of FA-PEG4000-L liposome group was about 3.6 and 3.1 times higher than that of non-targeted liposome group and FA-PEG2000-L liposome group, with statistically significant difference (P < 0.01). The drug delivery efficiency of FA-PEG4000-L group in HepG2 cells was higher than that in FA-PEG2000-L and non-targeted groups, and the results indicated that Folate-PEG4000-CHEMS can promote the uptake of liposome by HepG2 cells in vitro. All in all, Folate-PEG4000-CHEMS could be applied in the preparation of folate targeted liposome, which could promote the uptake of liposome by HepG2 cells.
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It is found that gambogic acid can play anti-tumor effects through different mechanisms in a variety of tumor cells,including induce apoptosis,inhibit telomerase and topoisomerase activity,inhibit the expression of heat shock protein and channel protein,inhibit tumor angiogenesis and metastasis and reverse multidrug resistance.Gambogic acid is expected to become a new anti-tumor drug,still need to be further explored its value in the field of anti-tumor.
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Combination chemotherapy and nanoparticle drug delivery are two promising strategies in cancer treatment. The use of multiple therapeutic agents in combination provides synergistic effects among different drugs against cancer cells and suppresses drug resistance through distinct mechanisms of action.Nanocarriers can improve anti-tumor effects of drugs and reduce systemic toxicity through delivering drugs into the tumor tissue specially. Recently, many studies are aiming to encapsulate multiple agents into nanocarriers to optimize the anti-tumor effects. In the present review, the recent advances of nanoparticle platforms applied with co-delivering two or more drugs were summarized and the various combination strategies based on nanoparticles in oncology were discussed.
