5-Fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma via Activation of the p53 Pathway in the Orthotopic Transplant Mouse Model

Cheng, Mingrong; He, Bing; Wan, Tao; Zhu, Weiping; Han, Jing; Zha, Bingbing; Chen, Houxiang; Fengxiao, Yang; Li, Qing; Wang, Wei; Hu, Xu; Ye, Tao

doi:10.1371/journal.pone.0047115

Cited by 64 publications

(33 citation statements)

References 48 publications

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“…Results showed that these GC/5-FU nanoparticles had obvious targeting properties against liver cancer, and that they may regulate the distribution and metabolism of 5-FU in vivo, thereby significantly reducing the toxic side effects of 5-FU. 20 In this study, we successfully synthesized the GCGA/5-FU nanoparticle, and its characteristics were observed in vitro and in vivo. This study used GCGA/5-FU nanoparticles to treat mice with liver cancer, and results showed that GCGA/5-FU nanoparticles significantly inhibited tumor growth and attenuated the immune suppression induced by 5-FU.…”

Section: Cheng Et Almentioning

confidence: 98%

“…20 Figure 2A shows that GCGA/5-FU nanoparticles had the highest liver concentration, which was 1.65, 2.35, and 2.75 times the concentrations of the GA-CTS/5-FU, CTS/5-FU, and 5-FU nanoparticles, respectively. However, the concentration of 5-FU in lung, spleen, heart, brain, and muscle tissues decreased from the 5-FU, CTS/5-FU, and GA-CTS/5-FU groups to the GCGA/5-FU group, and this trend was consistent with the results from confocal microscopy, as shown in Figure 2B.…”

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confidence: 99%

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Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

Cheng¹,

Gao²,

Wang³

et al. 2013

IJN

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Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival.

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Section: Cheng Et Almentioning

confidence: 98%

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confidence: 99%

Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

Cheng¹,

Gao²,

Wang³

et al. 2013

IJN

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“…Other chemotherapeutic agents delivered using CSNPs include 5-fluorouracil (5-FU) and camptothecin (CPT) [53][54][55]. 5-FU is a cytotoxic drug, which interferes with nucleic acid synthesis, inhibits DNA synthesis and eventually halts cell growth [56].…”

Section: Chitosanmentioning

confidence: 99%

Nanoformulations for Therapy of Pancreatic and Liver Cancers

Souza

Ranjan

Towner

2015

Nanomedicine (Lond.)

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Pancreatic and liver cancers often have poor prognoses. Clinically, pancreatic and liver cancer requires early diagnosis, and surgery is often associated with tumor recurrence. Currently, chemotherapies are limited in their ability to accurately target the tumors, and are associated with significant toxicity in patients. Targeting of chemotherapy can be improved by encapsulation in nanocarriers. A variety of preclinical studies indicate relatively superior therapeutic outcomes compared with drug alone therapy. Targeted nanoparticle imaging agents may also additionally facilitate better diagnosis and improve patient outcomes. This review discusses the nanoformulations that are under investigation (mainly preclinical studies, but also with some current clinical trial examples) against pancreatic and liver cancers, understands the challenges and provides future perspectives.

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“…We found that the GC/5-FU nanoparticles specifically target the liver and liver cancer cells, and that the deficiency of GC/5-FU nanoparticles increased the concentration of 5-FU in normal liver tissues [18]. Therefore, we synthesized nanomaterials targeting liver cancer based on preliminary research that aimed to improve liver cancer targeting and reduce the drug concentrations in liver tissue.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Biotin-Modified Galactosylated Chitosan Nanoparticles and Their Characteristics in Vitro and in Vivo

Cheng

Zhi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Our previous study found that a nanoparticle drug delivery system that operates as a drug carrier and controlled release system not only improves the efficacy of the drugs but also reduces their side effects. However, this system could not efficiently target hepatoma cells. The aim of this study was to synthesize biotin-modified galactosylated chitosan nanoparticles (Bio-GC) and evaluate their characteristics in vitro and in vivo. Methods: Bio-GC nanomaterials were synthesized, and confirmed by fourier transform infrared spectroscopy (FT-IR) and hydrogen-¹ nuclear magnetic resonance (¹H-NMR). The liver position and cancer target property of Bio-GC nanoparticles in vitro and in vivo was tested by confocal laser and small animal imaging system. The characteristics of Bio-GC/5-fluorouracil (5-FU) nanoparticles in vitro and in vivo were explored by cell proliferation, migration and cytotoxicity test, or by animal experiment. Results: Bio-GC nanoparticles were synthesized with biodegradable chitosan as the nanomaterial skeleton with biotin and galactose grafts. Bio-GC was confirmed by FT-IR and ¹H-NMR. Bio-GC/5-FU nanoparticles were synthesized according to the optimal mass ratio for Bio-GC/5-FU (1: 4) and had a mean particle size of 81.1 nm, zeta potential of +39.2 mV, and drug loading capacity of 8.98%. Bio-GC/5-FU nanoparticles had sustained release properties (rapid, steady, and slow release phases). Bio-GC nanoparticles targeted liver and liver cancer cell in vitro and in vivo, and this was confirmed by confocal laser scanning and small animal imaging system. Compared with GC/5-FU nanoparticles, Bio-GC/5-FU nanoparticles showed more specific cytotoxic activity in a dose- and time-dependent manner and a more obvious inhibitory effect on the migration of liver cancer cells. In addition, Bio-GC/5-FU nanoparticles significantly prolonged the survival time of mice in orthotopic liver cancer transplantation model compared with other 5-FU nanoparticles or 5-FU alone. Bio-GC (0.64%) nanomaterial had no obvious cytotoxic effects on cells; thus, the concentration of Bio-GC/5-FU nanoparticles used was only 0.04% and showed no toxic effects on the cells. Conclusion: Bio-GC is a liver- and cancer-targeting nanomaterial. Bio-GC/5-FU nanoparticles as drug carriers have stronger inhibitory effects on the proliferation and migration of liver cancer cells compared with 5-FU in vitro and in vivo.

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5-Fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma via Activation of the p53 Pathway in the Orthotopic Transplant Mouse Model

Cited by 64 publications

References 48 publications

Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

Nanoformulations for Therapy of Pancreatic and Liver Cancers

Synthesis of Biotin-Modified Galactosylated Chitosan Nanoparticles and Their Characteristics in Vitro and in Vivo

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