Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Feb 20;9(5):1426-1452.
doi: 10.7150/thno.31683. eCollection 2019.

Evaluation of Polymer Nanoformulations in Hepatoma Therapy by Established Rodent Models

Qilong Wang  1   2 , Ping Zhang  1 , Zhongmin Li  2   3 , Xiangru Feng  2   4 , Chengyue Lv  2   4 , Huaiyu Zhang  2   3 , Haihua Xiao  5 , Jianxun Ding  2   4 , Xuesi Chen  2   4
Affiliations
Review

Evaluation of Polymer Nanoformulations in Hepatoma Therapy by Established Rodent Models

Qilong Wang et al. Theranostics. .

Abstract

Hepatoma is one of the most severe malignancies usually with poor prognosis, and many patients are insensitive to the existing therapeutic agents, including the drugs for chemotherapy and molecular _targeted therapy. Currently, researchers are committed to developing the advanced formulations with controlled drug delivery to improve the efficacy of hepatoma therapy. Numerous inoculated, induced, and genetically engineered hepatoma rodent models are now available for formulation screening. However, animal models of hepatoma cannot accurately represent human hepatoma in terms of histological characteristics, metastatic pathways, and post-treatment responses. Therefore, advanced animal hepatoma models with comparable pathogenesis and pathological features are in urgent need in the further studies. Moreover, the development of nanomedicines has renewed hope for chemotherapy and molecular _targeted therapy of advanced hepatoma. As one kind of advanced formulations, the polymer-based nanoformulated drugs have many advantages over the traditional ones, such as improved tumor selectivity and treatment efficacy, and reduced systemic side effects. In this article, the construction of rodent hepatoma model and much information about the current development of polymer nanomedicines were reviewed in order to provide a basis for the development of advanced formulations with clinical therapeutic potential for hepatoma.

Keywords: chemotherapy; drug delivery; hepatoma; molecular _targeted therapy; polymer nanoparticle; rodent model.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Scheme 1
Scheme 1
Schematic illustration of rodent hepatoma models of various types and therapy using different polymer-based nanoplatforms.
Figure 1
Figure 1
Trends in published articles on application of polymer nanoformulations in treatment of hepatoma from 1998 to 2018 included in Web of Science Core Collection. The search topic is ((liver cancer OR liver carcinoma OR hepato* carcinoma OR hepatoma) AND (nano*) AND (polym* OR macromolecul*) AND (*therapy)).
Figure 2
Figure 2
Preparation process of DOX-loaded PMLG7-b-PLGA22 and PGLG7-b-PLGA22 micelles and evaluation of the antitumor efficacy . (A) Preparation and _targeted delivery of micelles assembled from glycopeptide and DOX. (B) Antitumor efficacies in vivo, (C) and body weight changes treated with PBS, DOX, and micelles from PMLG7-b-PLGA22/DOX and PGLG7-b-PLGA22/DOX. Evaluation of (D) ALT, (E) AST, (F) BUN, (G) Cr, (H) CK, and (I) LDH levels after all the treatments of PBS, DOX, and nanomedicines from PMLG7-b-PLGA22/DOX and PGLG7-b-PLGA22/DOX. Copyright 2013. Reproduced with permission from Elsevier Ltd.
Figure 3
Figure 3
Preparation of mPEG-P(LP-co-LC) nanogel and determination of the antitumor effect . (A) Synthetic pathway for mPEG-P(LP-co-LC) nanogel, illustrations of DOX encapsulation by nanogel, and its circulation, intratumoral accumulation, endocytosis, and _targeting intracellular DOX release after intravenous injection. (B) Ex vivo DOX fluorescence images of major visceral organs and tumor isolated at 6 or 12 h post-injection of NS, free DOX·HCl, or NG/DOX at a dose of 6.0 mg DOX·HCl equivalent per kg body weight toward BALB/c nude mice bearing a HepG2 tumor. (C) In vivo antitumor efficacies of NS, free DOX·HCl, and NG/DOX at a dose of 3.0 and 6.0 mg DOX·HCl equivalent per kg body weight. Copyright 2015. Reproduced with permission from Elsevier Ltd.
Figure 4
Figure 4
NG/DOX characterizations and DOX encapsulation, cell proliferation inhibition, and pharmacokinetics in vivo . (A) Synthetic pathway for mPEG-P(LG-co-LC) nanogel, DOX encapsulation by nanogel, and its characterization. (B) In vivo pharmacokinetic profiles after injection of DOX and NG/DOX in rats. (C) In vivo antitumor efficacy of NS, or of free DOX·HCl or NG/DOX at a dosage of 3.0 and 6.0 mg DOX equivalent per kg body weight toward H22-hepatoma-grafted BALB/c mouse model. The arrows indicated the treatment times. Each set of data was represented as mean ± SD (n = 10; * P < 0.05, & P < 0.01, # P < 0.001; i, DOX/3.0 vs NG/DOX/3.0; ii and iii, DOX/6.0 vs NG/DOX/6.0). Copyright 2017. Reproduced with permission from the Ivyspring International Publisher.
Figure 5
Figure 5
Fabrication of Dex-DOX conjugates and the assessments of antitumor activity and security . (A) Syntheses and self-assembly of Dex-DOX conjugates and characterization. (B) Tumor volumes and (C) survival rates of mice treated with Dex-O-DOX, Dex-b-DOX, or free DOX·HCl with NS as a control. Copyright 2015. Reproduced with permission from Elsevier Ltd.
Figure 6
Figure 6
Self-assembly, characterization, and antitumor efficacies of Dex-g-DOX . (A) Schematic illustration for some characterizations of Dex-g-DOX. (B) TNs with diameters > 3 mm; (C) TNs with diameters = 1 - 3 mm. Copyright 2016. Reproduced with permission from the American Chemical Society.
Figure 7
Figure 7
Fabrication process of PLGA, PLGA-5FU, and PLGA-5FU-SM5-1, and inhibition of tumor growth . (A) Schematic illustration of the fabrication process of PLGA, PLGA-5FU, and PLGA-5FU-SM5-1. (B) Serial bioluminescent images of the HCC-LM3-fLuc tumor-bearing nude mice that underwent PLGA-5FU-SM5-1 (a) PLGA-5FU (b) 5-FU (c) saline (d) treatment. (C) The quantitative results of cell apoptosis and (D) angiogenesis. Copyright 2014. Reproduced with permission from Elsevier Ltd.
Figure 8
Figure 8
Preparation of the long-circulating CPDG nanoassemblies and inhibition of tumor growth . (A) The long-circulating CPDG nanoassemblies synthesis and preparation process. (B) Growth profiles of tumor volume after i.v. injection of GEM solution and long-circulating CPDG nanoassemblies into the mice. (C) Tumor images following i.v. administration of GEM and long-circulating CPDG nanoassemblies to the mice. Copyright 2016. Reproduced with permission from Elsevier Ltd.
Figure 9
Figure 9
Preparation and fluorescence images of nanomaterials in different treatment groups . (A) Schematic presentation of the synthesis of Gal-P123 and preparation of LPG-modified Gal-P123 modified LPG. (B) Fluorescence images of organs excised at 12 h post injection of DIR solution, DiR-labeled liposome (DiR-LS), DiR-labeled Pluronic P123 modified liposome (DiR-LP) and DiR-labeled Gal-P123 modified liposome (DiR-LPG). (C) Tumor volume of the mice. Copyright 2012. Reproduced with permission from Elsevier Ltd.
Figure 10
Figure 10
Preparation process of LbL-LCN/SF and safety comparison of different treatments . (A) Schematic representation of fabrication process of LbL-LCN/SF. (B) Effects of free SF, LCN, LCN/SF, and LbL-LCN/SF on hemolytic toxicity. In vitro cytotoxicity of control (blank LbL-LCN), free SF, and LbL-LCN/SF on HepG2 cell lines following 24 h (C) and 72 h incubation (D). Copyright 2015. Reproduced with permission from the American Chemical Society.
Figure 11
Figure 11
Preparation process of SF-loaded _targeted polymeric nanoparticle (NP-SF-Ab) and tumor volume comparison of different formulations . (A) Schematic representation of the NP-SF-Ab fabricated from SF, TPGS-b-PCL, and Pluronic P123-Mal by nanoprecipitation method followed with conjugating anti-GPC3 antibody. (B) Tumor volume changes after treatment with saline, SF, NP-SF, and NP-SF-Ab. (C) Tumor images of groups treated with saline, SF, NP-SF, and NP-SF-Ab before and after treatment at day 14. Copyright 2018. Reproduced with permission from Elsevier Ltd.
Figure 12
Figure 12
Preparation of the iNP-VT nanoassemblies and inhibition of tumor growth . (A) Schematic illustration showing the reformulation and self-assembly of VT into PEG-PLGA NPs. (B) Tumor growth curves of different groups. NP-VT and iNP-VT were i.v. injected on day 0, 2, 4, 6, and 8. The blue and green arrows represent the day on which the i.v. and p.o. injections were performed, respectively. (C) Representative images of BEL-7402 after 16 days of treatment. Copyright 2016. Reproduced with permission from the American Chemical Society.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Thomas MB, Zhu AX. Hepatocellular carcinoma: The need for progress. J Clin Oncol. 2005;23:2892–9. - PubMed
    1. Vogel A, Cervantes A, Chau I, Daniele B, Llovet J, Meyer T. et al. Hepatocellular carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29:238–55. - PubMed
    1. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J. et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: A 2017 update. Hepatol Int. 2017;11:317–70. - PMC - PubMed
    1. Chen J, Ding J, Xiao C, Zhuang X, Chen X. Emerging antitumor applications of extracellularly reengineered polymeric nanocarriers. Biomater Sci. 2015;3:988–1001. - PubMed
    1. Ding J, Shi F, Li D, Chen L, Zhuang X, Chen X. Enhanced endocytosis of acid-sensitive doxorubicin derivatives with intelligent nanogel for improved security and efficacy. Biomater Sci. 2013;1:633–46. - PubMed

Publication types

MeSH terms

  NODES
admin 1
INTERN 4
twitter 2