Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice

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

doi:10.4161/cbt.22001

Cited by 14 publications

(6 citation statements)

References 29 publications

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“…Starting from this interesting work, it was developed the idea of using galactosylated chitosan for the therapy of HCC. Cheng et al developed galactosylated chitosan nanoparticles containing 5-fluorouracil, a cytotoxic drug used for the treatment of solid tumors such as liver cancer [70][71][72]. 5-fluorouracil is rapidly metabolized, and its long-term therapy is associated with some important side effects.…”

Section: Galactosylated Chitosansmentioning

confidence: 99%

“…The results obtained indicated that galactosylated chitosan is a good polymer for the preparation of 5-fluorouracil loaded nanoparticles, that are characterized by a sustained drug release capacity. Drug loaded nanoparticles inhibited tumor growth in an in vivo model of liver cancer (mouse) more markedly than 5-fluorouracil alone [70][71][72].…”

Section: Galactosylated Chitosansmentioning

confidence: 99%

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Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

et al. 2020

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Chitosan nanoparticles are well-known delivery systems widely used as polymeric carriers in the field of nanomedicine. Chitosan is a carbohydrate of natural origin: it is a biodegradable, biocompatible, mucoadhesive, polycationic polymer and it is endowed with penetration enhancer properties. Furthermore, it can be easily derivatized. Hepatocellular carcinoma (HCC) represents a remarkable health problem because current therapies, that include surgery, liver transplantation, trans-arterial embolization, chemoembolization and chemotherapy, present significant limitations due to the high risk of recurrence, to a lack of drug selectivity and to other serious side effects. Therefore, there is the need for new therapeutic strategies and for improving the liver-targeting to HCC. Nanomedicine consists in the use of nanoscale carriers as delivery systems to target and deliver drugs and/or diagnostic agents to specific organs or tissues. Chitosan and its derivatives can be successfully used in the preparation of nanoparticles that, for their peculiar surface-properties, can specifically interact with liver tumor, by passive and active targeting. This review concerns the use of chitosan nanoparticles for the therapy and theranostics of HCC and liver-targeting.

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Section: Galactosylated Chitosansmentioning

confidence: 99%

Section: Galactosylated Chitosansmentioning

confidence: 99%

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

et al. 2020

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“…Consequently, the success of gene therapy depends largely on the development of a safe and effective gene delivery system [ 9 ]. Galactosylated chitosan was synthesized from chitosan and galactose in the previous study conducted by our group, and the gene was successfully transfected in hepatocarcinoma tissue [ 10 , 11 ]. In addition to the cancer cells, this formulation exhibits similar targeting efficacy for normal liver cells.…”

Section: Introductionmentioning

confidence: 99%

Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer

Cheng

Zhu

Li³

et al. 2017

Oncotarget

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The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo.

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“…Asialoglycoprotein receptors (ASGP‐R1 and R2), which are overexpressed in hepatocellular cancer cells, are favorable candidates for HCC‐targeting drug delivery. [ 12b,18 ] Herein, galactose, a ligand for ASGPRs, was chosen to functionalize the lipopolyplexes to further enhance tumor accumulation. [ 19 ] The in vivo real‐time distribution of lipopolyplexes was tracked on HCC PDX‐bearing BALB/c mice after a single intravenous injection of DiR‐loaded SLP (SLP/DiR) or Gal‐SLP (Gal‐SLP/DiR).…”

Section: Resultsmentioning

confidence: 99%

Self‐Activated Cascade‐Responsive Sorafenib and USP22 shRNA Co‐Delivery System for Synergetic Hepatocellular Carcinoma Therapy

Ling

Shan

et al. 2021

Advanced Science

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Resistance to sorafenib severely hinders its effectiveness against hepatocellular carcinoma (HCC). Cancer stemness is closely connected with resistance to sorafenib. Methods for reversing the cancer stemness remains one of the largest concerns in research and the lack of such methods obstructs current HCC therapeutics. Ubiquitin‐specific protease 22 (USP22) is reported to play a pivotal role in HCC stemness and multidrug resistance (MDR). Herein, a galactose‐decorated lipopolyplex (Gal‐SLP) is developed as an HCC‐targeting self‐activated cascade‐responsive nanoplatform to co‐delivery sorafenib and USP22 shRNA (shUSP22) for synergetic HCC therapy. Sorafenib, entrapped in the Gal‐SLPs, induced a reactive oxygen species (ROS) cascade and triggered rapid shUSP22 release. Thus, Gal‐SLPs dramatically suppressed the expression of USP22. The downregulation of USP22 suppresses multidrug resistance‐associated protein 1 (MRP1) to induce intracellular sorafenib accumulation and hampers glycolysis of HCC cells. As a result, Gal‐SLPs efficiently inhibit the viability, proliferation, and colony formation of HCC cells. A sorafenib‐insensitive patient‐derived xenograft (PDX) model is established and adopted to evaluate in vivo antitumor effect of Gal‐SLPs. Gal‐SLPs exhibit potent antitumor efficiency and biosafety. Therefore, Gal‐SLPs are expected to have great potential in the clinical treatment of HCC.

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Preliminary pharmacology of galactosylated chitosan/5-fluorouracil nanoparticles and its inhibition of hepatocellular carcinoma in mice

Cited by 14 publications

References 29 publications

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer

Self‐Activated Cascade‐Responsive Sorafenib and USP22 shRNA Co‐Delivery System for Synergetic Hepatocellular Carcinoma Therapy

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