A self-assembly nanodrug delivery system based on amphiphilic low generations of PAMAM dendrimers-ursolic acid conjugate modified by lactobionic acid for HCC targeting therapy

Shen, Zhichun; Li, Bowen; Liu, Yajun; Zheng, Guirong; Guo, Yan; Zhao, Rui; Jiang, Kai; Fan, Lulu; Shao, Jingwei

doi:10.1016/j.nano.2017.10.007

Cited by 37 publications

(29 citation statements)

References 29 publications

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“…Further, we found UA-PMs could suppress the tumor growth of H22 xenograft and prolong the survival time of the tumor-bearing mice. These results are consistent with the previous report [6,8,12,13].…”

Section: Discussionsupporting

confidence: 94%

“…However, for the further clinical application, the formulation should be further optimized to improve the entrapment efficiency, drug-loading rate. On the other hand, maybe there is another way to develop UA formulation to conjugate UA with the amphiphilic block copolymers to form UA-PEG-PLA and further use it to prepare micelles [6,[12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

“…Among them, ursolic acid (3β-hydroxy-urs-12-en-28-oic acid, UA) as one kind of pentacyclic triterpenoid is widely distributed in a variety of natural plants, such as loquat and glossy privet fruit. UA shows a variety of biological effects like anti-tumor [4,5,6] and anti-angiogenesis [7]. It has been proved to be effective in anti-hepatocellular carcinoma [8].…”

Section: Ivyspringmentioning

confidence: 99%

“…It has been proved to be effective in anti-hepatocellular carcinoma [8]. Moreover, it is low toxicity and became the hot spot in the study of anticancer drugs in recent years [6,9]. Therefore, we chose UA to develop the drug delivery system of UA-loaded polymer micelles (UA-PMs) to overcome the disadvantages of UA in clinical application.…”

Section: Ivyspringmentioning

confidence: 99%

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Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma

Zhou

Liu

et al. 2019

J. Cancer

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Ursolic acid (UA) is widely found in many dietary plants, which has been proved to be effective in cancer therapy. But unfortunately its hydrophobic property limits its clinical application. Polymer micelles (PMs) are constructed from amphiphilic block copolymers that tend to self-assemble and form the unique core-shell structure consisting of a hydrophilic corona outside and a hydrophobic inner core. PMs could entrap the hydrophobic substance into its hydrophobic inner core for solubilizing these poorly water-soluble drugs and it is widely applied as a novel nano-sized drug delivery system. This study aimed to develop the drug delivery system of UA-loaded polymer micelles (UA-PMs) to overcome the disadvantages of UA in clinical application thus enhancing antitumor effect on hepatocellular carcinoma. UA-PMs was prepared and characterized for the physicochemical properties. It was investigated the cell-growth inhibition effect of UA-PMs against the human hepatocellular carcinoma cell line HepG2 and human normal liver cell line L-02. UA-PMs was evaluated about the in vivo toxicity and the antitumor activity. We took a diblock copolymer of methoxy poly (ethylene glycol)-poly(L-lactic acid) (mPEG-PLA) as carrier material to prepare UA-PMs by the thin-film dispersion method. MTT assay and wound-healing assay were investigated to assess the inhibition effect of UA-PMs against HepG2 cells on cell-growth and cell-migration. Further, we chose KM mice for the acute toxicity experiment and assessed the antitumor effect of UA-PMs on the H22 tumor xenograft. UA-PMs could markedly inhibit the proliferation and migration of HepG2 cells. In vivo study showed that UA-PMs could significantly inhibit the growth of H22 xenograft and prolong the survival time of tumor-bearing mice. It demonstrated that UA-PMs possess great potential in liver cancer therapy and may enlarge the application of UA in clinical therapy.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

Section: Ivyspringmentioning

confidence: 99%

See 2 more Smart Citations

Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma

Zhou

Liu

et al. 2019

J. Cancer

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“…The data also validated that improvement of the cellular uptake efficiency of NPs was ascribed to LA group that targeted to HepG2 cells by ASGPR. The results were consistent with the previous research (Dong et al., 2017; Shen et al., 2018).…”

Section: Resultssupporting

confidence: 94%

Multifunctional nanoplatform based on star-shaped copolymer for liver cancer targeting therapy

Gong

Zheng²,

He³

et al. 2019

Drug Delivery

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With high morbidity and death rates, liver cancer has become one of the most common cancers in the world. But, most chemotherapeutic anticancer drugs have high toxicity as well as low specificity. To improve the treatment modalities and enhance the therapeutic effect of liver cancer, a brand new liver-targeting nanoparticle (NP), Ent-11a-hydroxy-15-oxo-kaur-16-en-19-oic acid (5 F)-loaded cholic acid (CA)-functionalized star-shaped poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-lactobionic acid (LA) (5 F-loaded CA-PLGA-PEG-LA), was developed. The particle size, zeta potential, size distribution, surface morphology, drug loading content, drug encapsulation efficiency and drug release of 5 F-loaded NPs were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be internalized by HepG2 cells. Furthermore, the cellular uptake efficiency of coumarin 6loaded CA-PLGA-PEG-LA NPs was much better in compare with that of CA-PLGA-PEG and CA-PLGA NPs. Moreover, LA-conjugated NPs (CA-PLGA-PEG-LA NPs) enhanced fluorescence of HepG2 cells via ligand-mediated endocytosis. The antitumor effects of 5 F-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted 5 F-loaded CA-PLGA-PEG-LA NPs were significantly superior to free 5 F and 5 F-loaded CA-PLGA-PEG NPs. All the results indicated the 5 F-loaded CA-PLGA-PEG-LA NPs can be employed as a novel potentially targeting drug delivery system for liver cancer therapy.

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Nanotherapeutics of Phytoantioxidants in Cancer

Shah¹,

Patel²,

Parmar³

2022

Phytoantioxidants and Nanotherapeutics

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A self-assembly nanodrug delivery system based on amphiphilic low generations of PAMAM dendrimers-ursolic acid conjugate modified by lactobionic acid for HCC targeting therapy

Cited by 37 publications

References 29 publications

Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma

Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma

Multifunctional nanoplatform based on star-shaped copolymer for liver cancer targeting therapy

Nanotherapeutics of Phytoantioxidants in Cancer

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