Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2018 Volume 42 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2018 Volume 42 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery

Corrigendum in: /10.3892/ijmm.2019.4308
  • Authors:
    • Youbei Qiao
    • Bao Liu
    • Yifan Peng
    • Erlong Ji
    • Hong Wu
  • View Affiliations / Copyright

    Affiliations: Department of Pharmaceutical Analysis, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Shiquanhe Medical Station, A'li, Tibet 859000, P.R. China
  • Pages: 3495-3502
    |
    Published online on: September 25, 2018
       https://doi.org/10.3892/ijmm.2018.3893
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Poly (β‑malic acid), referred to as PMLA, has been synthesized and introduced as a polymeric drug carrier due to its desirable biological properties. In the present study, a novel pH‑sensitive polymer‑drug conjugate based on PMLA, PMLA‑Hz‑doxorubicin (DOX), was prepared, and another conjugate, PMLA‑ami‑DOX, was synthesized as a comparison. The structures, conjugation efficiency, and drug release properties of the prodrugs were determined. The cytotoxicity and cell uptake were assessed using the HT1080 human fibrosarcoma cell line as an in vitro cell model. The release of DOX in the two conjugates were pH‑dependent in PBS buffer at a pH of 5.6, 6.0, 6.8 and 7.4. The quantity of drug released increased with the decrease in pH, and PMLA‑ami‑DOX released twice as much as PMLA‑Hz‑DOX (12 h). The cytotoxicity of PMLA‑Hz‑DOX at pH 7.4 was lower than that of free DOX and increased with the decrease in pH, indicating that the cytotoxicity of PMLA‑Hz‑DOX was pH‑sensitive. Flow cytometry and confocal experiments confirmed the efficiency of the PMLA‑Hz‑DOX conjugate. Therefore, bonding DOX to PMLA via an acid‑sensitive hydrazone bond may be used to reduce its toxic side effects on normal tissues while responding to tumor pH and releasing the drug.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

View References

1 

Kopecek J: Polymer-drug conjugates: Origins, progress to date and future directions. Adv Drug Deliv Rev. 65:49–59. 2013. View Article : Google Scholar

2 

Larson N and Ghandehari H: Polymeric conjugates for drug delivery. Chem Mater. 24:840–853. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Li J, Yu F, Chen Y and Oupicky D: Polymeric drugs: Advances in the development of pharmacologically active polymers. J Control Release. 219:369–382. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Khandare J and Minko T: Polymer-drug conjugates: Progress in polymeric prodrugs. Prog Polym Sci. 31:359–397. 2006. View Article : Google Scholar

5 

Li C and Wallace S: Polymer-drug conjugates: Recent development in clinical oncology. Adv Drug Deliv Rev. 60:886–898. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Feng Q and Tong R: Anticancer nanoparticulate polymer-drug conjugate. Bioeng Transl Med. 1:277–296. 2016.PubMed/NCBI

7 

Canal F, Sanchis J and Vicent MJ: Polymer-drug conjugates as nano-sized medicines. Curr Opin Biotechnol. 22:894–900. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Lee BS, Vert M and Holler E: Water-soluble aliphatic polyesters: Poly(malic acid)s. Wiley-VCH Verlag GmbH & Co KGaA. 2005.

9 

Braud C, Bunel C and Vert M: Poly(β-malic acid): A new polymeric drug-carrier. Polymer Bulletin. 13:293–299. 1985. View Article : Google Scholar

10 

Loyer P and Cammas-Marion S: Natural and synthetic poly(malic acid)-based derivates: A family of versatile biopolymers for the design of drug nanocarriers. J Drug Target. 22:556–575. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Fernández CE, Mancera M, Holler E, Galbis JA and Muñoz-Guerra S: High molecular weight methyl ester of microbial poly(β,l-malic acid): Synthesis and crystallization. Polymer. 47:6501–6508. 2006. View Article : Google Scholar

12 

Martinez Barbosa ME, Cammas S, Appel M and Ponchel G: Investigation of the degradation mechanisms of poly(malic acid) esters in vitro and their related cytotoxicities on J774 macrophages. Biomacromolecules. 5:137–143. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Segal E and Satchi-Fainaro R: Design and development of polymer conjugates as anti-angiogenic agents. Adv Drug Deliv Rev. 61:1159–1176. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Ljubimova JY, Portilla-Arias J, Patil R, Ding H, Inoue S, Markman JL, Rekechenetskiy A, Konda B, Gangalum PR, Chesnokova A, et al: Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates for triple-negative breast cancer treatment. J Drug Target. 21:956–967. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Lee BS, Fujita M, Khazenzon NM, Wawrowsky KA, Wachsmann-Hogiu S, Farkas DL, Black KL, Ljubimova JY and Holler E: Polycefin, a new prototype of a multifunctional nano-conjugate based on poly(beta-L-malic acid) for drug delivery. Bioconjug Chem. 17:317–326. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Ding H, Inoue S, Ljubimov AV, Patil R, Portilla-Arias J, Hu J, Konda B, Wawrowsky KA, Fujita M, Karabalin N, et al: Inhibition of brain tumor growth by intravenous poly (beta-L-malic acid) nanobioconjugate with pH-dependent drug release [corrected]. Proc Natl Acad Sci USA. 107:18143–18148. 2010. View Article : Google Scholar

17 

Qiao YB, Duan X, Fan L, Li W, Wu H and Wang YK: Synthesis of controlled molecular weight poly (beta-malic acid) and conjugation with HCPT as a polymeric drug carrier. J Polym Res. 21:3972014. View Article : Google Scholar

18 

Yang T, Li W, Duan X, Zhu L, Fan L, Qiao Y and Wu H: Preparation of two types of polymeric micelles based on poly(beta-L-malic acid) for antitumor drug delivery. PLoS One. 11:e01626072016. View Article : Google Scholar

19 

Guo X, Shi C, Wang J, Di S and Zhou S: pH-triggered intracellular release from actively targeting polymer micelles. Biomaterials. 34:4544–4554. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Chen B, Dai W, He B, Zhang H, Wang X, Wang Y and Zhang Q: Current multistage drug delivery systems based on the tumor microenvironment. Theranostics. 7:538–558. 2017. View Article : Google Scholar : PubMed/NCBI

21 

Huang X, Liao W, Zhang G, Kang S and Zhang CY: pH-sensitive micelles self-assembled from polymer brush (PAE-g-cholesterol)- b-PEG-b-(PAE-g-cholesterol) for anticancer drug delivery and controlled release. Int J Nanomedicine. 12:2215–2226. 2017. View Article : Google Scholar :

22 

Wang X, Yang Y, Zhuang Y, Gao P, Yang F, Shen H, Guo H and Wu D: Fabrication of pH-responsive nanoparticles with an AIE feature for imaging intracellular drug delivery. Biomacromolecules. 17:2920–2929. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Zhao D, Xu JQ, Yi XQ, Zhang Q, Cheng SX, Zhuo RX and Li F: pH-activated targeting drug delivery system based on the selective binding of phenylboronic acid. ACS Appl Mater Interfaces. 8:14845–14854. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Sun T, Zhang YS, Pang B, Hyun DC, Yang M and Xia Y: Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed Engl. 53:12320–12364. 2014.PubMed/NCBI

25 

Karimi M, Eslami M, Sahandi-Zangabad P, Mirab F, Farajisafiloo N, Shafaei Z, Ghosh D, Bozorgomid M, Dashkhaneh F and Hamblin MR: pH-sensitive stimulus-responsive nanocarriers for targeted delivery of therapeutic agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 8:696–716. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Qian CG, Chen YL, Feng PJ, Xiao XZ, Dong M, Yu JC, Hu QY, Shen QD and Gu Z: Conjugated polymer nanomaterials for ther-anostics. Acta Pharmacol Sin. 38:764–781. 2017. View Article : Google Scholar : PubMed/NCBI

27 

Zhu YJ and Chen F: pH-responsive drug-delivery systems. Chem Asian J. 10:284–305. 2015. View Article : Google Scholar

28 

Wang Z, Deng X, Ding J, Zhou W, Zheng X and Tang G: Mechanisms of drug release in pH-sensitive micelles for tumour targeted drug delivery system: A review. Int J Pharm. 535:253–260. 2018. View Article : Google Scholar

29 

Lee ES, Oh KT, Kim D, Youn YS and Bae YH: Tumor pH-responsive flower-like micelles of poly(L-lactic acid)-b-poly(ethylene glycol)-b-poly(L-histidine). J Control Release. 123:19–26. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Zhang H, Li F, Yi J, Gu C, Fan L, Qiao Y, Tao Y, Cheng C and Wu H: Folate-decorated maleilated pullulan-doxorubicin conjugate for active tumor-targeted drug delivery. Eur J Pharm Sci. 42:517–526. 2011. View Article : Google Scholar : PubMed/NCBI

31 

National Pharmacopoeia Committee: Pharmacopoeia of People's Republic of China. China Medical Science Press, Beijing Part. 2:9552015.

32 

Zhou Q, Hou Y, Zhang L, Wang J, Qiao Y, Guo S, Fan L, Yang T, Zhu L and Wu H: Dual-pH sensitive charge-reversal nanocomplex for tumor-targeted drug delivery with enhanced anticancer activity. Theranostics. 7:1806–1819. 2017. View Article : Google Scholar : PubMed/NCBI

33 

Mintzer MA and Simanek EE: Nonviral vectors for gene delivery. Chem Rev. 109:259–302. 2009. View Article : Google Scholar

34 

Aoshima Y, Hokama R, Sou K, Sarker SR, Iida K, Nakamura H, Inoue T and Takeoka S: Cationic amino acid based lipids as effective nonviral Gene delivery vectors for primary cultured neurons. ACS Chem Neurosci. 4:1514–1519. 2013. View Article : Google Scholar : PubMed/NCBI

35 

Zhao G, Long L, Zhang L, Peng M, Cui T, Wen X, Zhou X, Sun L and Che L: Smart pH-sensitive nanoassemblies with cleavable PEGylation for tumor targeted drug delivery. Sci Rep. 7:33832017. View Article : Google Scholar : PubMed/NCBI

36 

Liu Y, Li D, Guo X, Xu H, Li Z, Zhang Y, Song C, Fan R, Tang X and Zhang Z: A pH-responsive prodrug delivery system of 10-HCPT for controlled release and tumor targeting. Int J Nanomedicine. 12:2227–2242. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qiao Y, Liu B, Peng Y, Ji E and Wu H: Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308. Int J Mol Med 42: 3495-3502, 2018.
APA
Qiao, Y., Liu, B., Peng, Y., Ji, E., & Wu, H. (2018). Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308. International Journal of Molecular Medicine, 42, 3495-3502. https://doi.org/10.3892/ijmm.2018.3893
MLA
Qiao, Y., Liu, B., Peng, Y., Ji, E., Wu, H."Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308". International Journal of Molecular Medicine 42.6 (2018): 3495-3502.
Chicago
Qiao, Y., Liu, B., Peng, Y., Ji, E., Wu, H."Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308". International Journal of Molecular Medicine 42, no. 6 (2018): 3495-3502. https://doi.org/10.3892/ijmm.2018.3893
Copy and paste a formatted citation
x
Spandidos Publications style
Qiao Y, Liu B, Peng Y, Ji E and Wu H: Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308. Int J Mol Med 42: 3495-3502, 2018.
APA
Qiao, Y., Liu, B., Peng, Y., Ji, E., & Wu, H. (2018). Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308. International Journal of Molecular Medicine, 42, 3495-3502. https://doi.org/10.3892/ijmm.2018.3893
MLA
Qiao, Y., Liu, B., Peng, Y., Ji, E., Wu, H."Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308". International Journal of Molecular Medicine 42.6 (2018): 3495-3502.
Chicago
Qiao, Y., Liu, B., Peng, Y., Ji, E., Wu, H."Preparation and biological evaluation of a novel pH-sensitive poly (β-malic acid) conjugate for antitumor drug delivery Corrigendum in /10.3892/ijmm.2019.4308". International Journal of Molecular Medicine 42, no. 6 (2018): 3495-3502. https://doi.org/10.3892/ijmm.2018.3893
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team