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Article

Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles

  • Authors:
    • Chuntang Sun
    • Le Zhou
    • Maling Gou
    • Shuai Shi
    • Tao Li
    • Jinyi Lang
  • View Affiliations / Copyright

    Affiliations: Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, P.R. China, Department of Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China, Institute of Biomedical Engineering, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
  • Pages: 3600-3606
    |
    Published online on: April 15, 2016
       https://doi.org/10.3892/or.2016.4748
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Abstract

Doxorubicin (Dox) is a broad-spectrum antitumor drug used for the treatment of many types of malignant tumors. Although it possesses powerful antitumor activity, its clinical application is seriously encumbered by its unselective distribution and systemic toxicities, particularly myocardial toxicity. Thus, it is imperative to modify Dox to decrease its systemic toxicities and improve its therapeutic index. In the present study, we adopted a novel type of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to encapsulate Dox to prepare Dox-loaded MPEG-PCL (Dox/MPEG-PCL) nanoparticles by a controllable self-assembly process. The cellular uptake efficiency and cell proliferation inhibition of the Dox/MPEG-PCL nanoparticles were examined. The antitumor activity of the Dox/MPEG-PCL nanoparticles was tested on a multiple pulmonary metastasis model of melanoma on C57BL/6 mice. Systemic toxicities and survival time were compared between the mice treated with the Dox/MPEG-PCL nanoparticles and free Dox. The potential myocardial toxicity of the Dox/MPEG-PCL nanoparticles was investigated using a prolonged observation period. Encapsulation of Dox in MPEG-PCL nanoparticles significantly improved the cellular uptake and cell proliferation inhibition of Dox in vivo. Intravenous injection of Dox/MPEG-PCL nanoparticles obtained significant inhibition of the growth and metastasis of melanoma in the lung and prolonged survival time compared with free Dox (P<0.05). The Dox/MPEG-PCL nanoparticles did not show obvious additional systemic toxicities compared with free Dox during the treatment time. During the prolonged observation period, obvious decreased cardiac toxicity was observed in the Dox/MPEG-PCL nanoparticle-treated mice compared with that observed in the free Dox-treated mice. These results indicated that encapsulating Dox with MPEG-PCL micelles could significantly promote its antitumor activity and reduce its toxicity to the myocardium.
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1 

Azim HA, Santoro L, Bociek RG, Gandini S, Malek RA and Azim HA Jr: High dose intensity doxorubicin in aggressive non-Hodgkin's lymphoma: A literature-based meta-analysis. Ann Oncol. 21:1064–1071. 2010. View Article : Google Scholar

2 

Sauter C: Doxorubicin adjuvant combinations for breast cancer. Lancet. 342:1550–1551. 1993. View Article : Google Scholar : PubMed/NCBI

3 

Staropoli N, Ciliberto D, Botta C, Fiorillo L, Grimaldi A, Lama S, Caraglia M, Salvino A, Tassone P and Tagliaferri P: Pegylated liposomal doxorubicin in the management of ovarian cancer: A systematic review and metaanalysis of randomized trials. Cancer Biol Ther. 15:707–720. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Grenader T, Goldberg A, Hadas-Halperin I and Gabizon A: Long-term response to pegylated liposomal doxorubicin in patients with metastatic soft tissue sarcomas. Anticancer Drugs. 20:15–20. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Heger Z, Cernei N, Kudr J, Gumulec J, Blazkova I, Zitka O, Eckschlager T, Stiborova M, Adam V and Kizek R: A novel insight into the cardiotoxicity of antineoplastic drug doxorubicin. Int J Mol Sci. 14:21629–21646. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Chatterjee K, Zhang J, Honbo N and Karliner JS: Doxorubicin cardiomyopathy. Cardiology. 115:155–162. 2010. View Article : Google Scholar :

7 

Wright J: Nanotechnology: Deliver on a promise. Nature. 509:S58–S59. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Gou M, Zheng X, Men K, Zhang J, Wang B, Lv L, Wang X, Zhao Y, Luo F, Chen L, et al: Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles. Pharm Res. 26:2164–2173. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Zheng L, Gou M, Zhou S, Yi T, Zhong Q, Li Z, He X, Chen X, Zhou L, Wei Y, et al: Antitumor activity of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) micelle-encapsulated doxorubicin against mouse melanoma. Oncol Rep. 25:1557–1564. 2011.PubMed/NCBI

10 

van Spriel AB, van Ojik HH, Bakker A, Jansen MJ and van de Winkel JG: Mac-1 (CD11b/CD18) is crucial for effective Fc receptor-mediated immunity to melanoma. Blood. 101:253–258. 2003. View Article : Google Scholar

11 

Tsai NM, Chen BM, Wei SL, Wu CW and Roffler SR: Anti-tumor immunoglobulin M increases lung metastasis in an experimental model of malignant melanoma. Clin Exp Metastasis. 20:103–109. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Bourzac K: Nanotechnology: Carrying drugs. Nature. 491:S58–S60. 2012. View Article : Google Scholar

13 

Aiken MJ, Suhag V, Garcia CA, Acio E, Moreau S, Priebat DA, Chennupati SP and Van Nostrand D: Doxorubicin-induced cardiac toxicity and cardiac rest gated blood pool imaging. Clin Nucl Med. 34:762–767. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Liu Y, Fang J, Kim YJ, Wong MK and Wang P: Codelivery of doxorubicin and paclitaxel by cross-linked multilamellar liposome enables synergistic antitumor activity. Mol Pharm. 11:1651–1661. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Green AE and Rose PG: Pegylated liposomal doxorubicin in ovarian cancer. Int J Nanomedicine. 1:229–239. 2006.

16 

Unsoy G, Khodadust R, Yalcin S, Mutlu P and Gunduz U: Synthesis of Doxorubicin loaded magnetic chitosan nanoparticles for pH responsive targeted drug delivery. Eur J Pharm Sci. 62:243–250. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Sanyakamdhorn S, Agudelo D and Tajmir-Riahi HA: Encapsulation of antitumor drug Doxorubicin and its analogue by chitosan nanoparticles. Biomacromolecules. 14:557–563. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Yang X, Grailer JJ, Rowland IJ, Javadi A, Hurley SA, Steeber DA and Gong S: Multifunctional SPIO/DOX-loaded wormlike polymer vesicles for cancer therapy and MR imaging. Biomaterials. 31:9065–9073. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Meng H, Liong M, Xia T, Li Z, Ji Z, Zink JI and Nel AE: Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line. ACS Nano. 4:4539–4550. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Jia Y, Yuan M, Yuan H, Huang X, Sui X, Cui X, Tang F, Peng J, Chen J, Lu S, et al: Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery. Int J Nanomedicine. 7:1697–1708. 2012. View Article : Google Scholar :

21 

Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D and Leroux JC: Block copolymer micelles: Preparation, characterization and application in drug delivery. J Control Release. 109:169–188. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Farokhzad OC, Jon S, Khademhosseini A, Tran TN, Lavan DA and Langer R: Nanoparticle-aptamer bioconjugates: A new approach for targeting prostate cancer cells. Cancer Res. 64:7668–7672. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Hudson SP, Padera RF, Langer R and Kohane DS: The biocompatibility of mesoporous silicates. Biomaterials. 29:4045–4055. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Chow EK, Zhang XQ, Chen M, Lam R, Robinson E, Huang H, Schaffer D, Osawa E, Goga A and Ho D: Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci Transl Med. 3:73ra212011. View Article : Google Scholar : PubMed/NCBI

25 

Canelas DA, Herlihy KP and DeSimone JM: Top-down particle fabrication: Control of size and shape for diagnostic imaging and drug delivery. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 1:391–404. 2009. View Article : Google Scholar

26 

Gupta AK and Gupta M: Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications. Biomaterials. 26:3995–4021. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Gupta AK and Wells S: Surface-modified superparamagnetic nanoparticles for drug delivery: Preparation, characterization, and cytotoxicity studies. IEEE Trans Nanobioscience. 3:66–73. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Agarwal A, Mackey MA, El-Sayed MA and Bellamkonda RV: Remote triggered release of doxorubicin in tumors by synergistic application of thermosensitive liposomes and gold nanorods. ACS Nano. 5:4919–4926. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Matsumura Y and Maeda H: A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46:6387–6392. 1986.PubMed/NCBI

30 

Sant S, Poulin S and Hildgen P: Effect of polymer architecture on surface properties, plasma protein adsorption, and cellular interactions of pegylated nanoparticles. J Biomed Mater Res A. 87:885–895. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Lu J, Jia H, Guo L, Zhang G, Cao Y, Yan H and Liu K: Zwitterionic polymeric micelles that undergo a pH-triggered positive charge for enhanced cellular uptake. Eur Polym J. 66:376–385. 2015. View Article : Google Scholar

32 

Gou M, Zheng X, Men K, Zhang J, Zheng L, Wang X, Luo F, Zhao Y, Zhao X, Wei Y, et al: Poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) nanoparticles: Preparation, characterization, and application in doxorubicin delivery. J Phys Chem B. 113:12928–12933. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Sun C, Zhou L, Gou M, Shi S, Li T and Lang J: Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles. Oncol Rep 35: 3600-3606, 2016.
APA
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., & Lang, J. (2016). Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles. Oncology Reports, 35, 3600-3606. https://doi.org/10.3892/or.2016.4748
MLA
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., Lang, J."Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles". Oncology Reports 35.6 (2016): 3600-3606.
Chicago
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., Lang, J."Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles". Oncology Reports 35, no. 6 (2016): 3600-3606. https://doi.org/10.3892/or.2016.4748
Copy and paste a formatted citation
x
Spandidos Publications style
Sun C, Zhou L, Gou M, Shi S, Li T and Lang J: Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles. Oncol Rep 35: 3600-3606, 2016.
APA
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., & Lang, J. (2016). Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles. Oncology Reports, 35, 3600-3606. https://doi.org/10.3892/or.2016.4748
MLA
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., Lang, J."Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles". Oncology Reports 35.6 (2016): 3600-3606.
Chicago
Sun, C., Zhou, L., Gou, M., Shi, S., Li, T., Lang, J."Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles". Oncology Reports 35, no. 6 (2016): 3600-3606. https://doi.org/10.3892/or.2016.4748
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