Back to Journals » International Journal of Nanomedicine » Volume 10 » Issue 1

PLGA-PLL-PEG-Tf-based targeted nanoparticles drug delivery system enhance antitumor efficacy via intrinsic apoptosis pathway

Authors Bao W, Liu R, Wang Y, Wang F, Xia G, Zhang H, Li X, Yin H, Chen B

Received 29 September 2014

Accepted for publication 18 November 2014

Published 12 January 2015 Volume 2015:10(1) Pages 557—566


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster

Wen Bao,1 Ran Liu,1 Yonglu Wang,1,2 Fei Wang,1 Guohua Xia,1 Haijun Zhang,1 Xueming Li,2 Haixiang Yin,2 Baoan Chen1

1Department of Hematology and Oncology, Key Medical Disciplines of Jiangsu Province, Zhongda Hospital, Medical School of Southeast University, 2College of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China

Abstract: Chemotherapy offers a systemic cancer treatment; however, it is limited in clinical administration due to its serious side effects. In cancer medicine, the use of nanoparticles (NPs) drug delivery system (DDS) can sustainedly release anticancer drug at the specific site and reduce the incidence of toxicity in normal tissues. In the present study, we aimed to evaluate the benefit of a novel chemotherapeutic DDS and its underlying mechanisms. Daunorubicin (DNR) was loaded into poly (lactic-co-glycolic acid) (PLGA)-poly-l-lysine (PLL)-polyethylene glycol (PEG)-transferrin (Tf) NPs to construct DNR-PLGA-PLL-PEG-Tf-NPs (DNR-loaded NPs) as a DDS. After incubating with PLGA-PLL-PEG-Tf-NPs, DNR, and DNR-loaded NPs, the leukemia K562 cells were collected and the intracellular concentration of DNR was detected by flow cytometry, respectively. Furthermore, the effect of drugs on the growth of tumors in K562 xenografts was observed and the relevant toxicity of therapeutic drugs on organs was investigated in vivo. Meanwhile, cell apoptosis in the excised xenografts was measured by transferase-mediated dUTP nick-end labeling assay, and the expression of apoptosis-related proteins, including Bcl-2, Bax, Caspase-9, Caspase-3, and cleaved-PARP, was determined by Western blotting analysis. Results showed that DNR-loaded NPs increased intracellular concentration of DNR in K562 cells in vitro and induced a remarkable improvement in anticancer activity in the xenografts in vivo. The expression of Bcl-2 protein was downregulated and that of Bax, Caspase-9, Caspase-3, and cleaved-PARP proteins were obviously upregulated in the DNR-loaded NPs group than that in other ones. Interestingly, pathological assessment showed no apparent damage to the main organs. In summary, the results obtained from this study showed that the novel NPs DDS could improve the efficacy of DNR in the treatment of leukemia and induce apoptosis via intrinsic pathway. Thus, it can be inferred that the new drug delivery may be a useful clinical tool.

Keywords: PLGA-PLL-PEG, daunorubicin, transferrin, K562 cells, apoptosis

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other articles by this author:

Tf-PEG-PLL-PLGA nanoparticles enhanced chemosensitivity for hypoxia-responsive tumor cells

Liu P, Zhang H, Wu X, Guo L, Wang F, Xia G, Chen B, Yin H, Wang Y, Li X

OncoTargets and Therapy 2016, 9:5049-5059

Published Date: 12 August 2016

Lobaplatin for the treatment of SK-MES-1 lung squamous cell line in vitro and in vivo

Zhang H, Chen R, Yang S, Liu W, Li K, Zhang H, Zhu X, Chen B

OncoTargets and Therapy 2016, 9:4215-4224

Published Date: 11 July 2016

Advances of wogonin, an extract from Scutellaria baicalensis, for the treatment of multiple tumors

Wu X, Zhang H, Salmani JMM, Fu R, Chen B

OncoTargets and Therapy 2016, 9:2935-2943

Published Date: 17 May 2016

Targeted multidrug-resistance reversal in tumor based on PEG-PLL-PLGA polymer nano drug delivery system

Guo L, Zhang H, Wang F, Liu P, Wang Y, Xia G, Liu R, Li X, Yin H, Jiang H, Chen B

International Journal of Nanomedicine 2015, 10:4535-4547

Published Date: 16 July 2015

Synthesis and characterization of tumor-targeted copolymer nanocarrier modified by transferrin

Liu R, Wang Y, Li X, Bao W, Xia G, Chen W, Cheng J, Xu Y, Guo L, Chen B

Drug Design, Development and Therapy 2015, 9:2705-2719

Published Date: 22 May 2015

Primary malignant lymphoma of the uterus and broad ligament: a case report and review of literature

Chen R, Yu Z, Zhang H, Ding J, Chen B

OncoTargets and Therapy 2015, 8:265-268

Published Date: 29 January 2015

Apoptosis selectively induced in BEL-7402 cells by folic acid-modified magnetic nanoparticles combined with 100 Hz magnetic field

Wen J, Jiang S, Chen Z, Zhao W, Yi Y, Yang R, Chen B

International Journal of Nanomedicine 2014, 9:2043-2050

Published Date: 23 April 2014

Clinical outcomes of transfusion-associated iron overload in patients with refractory chronic anemia

Gao C, Li L, Chen BA, Song HH, Cheng J, Zhang XP, Sun YY

Patient Preference and Adherence 2014, 8:513-517

Published Date: 22 April 2014

Readers of this article also read:

Emerging and future therapies for hemophilia

Carr ME, Tortella BJ

Journal of Blood Medicine 2015, 6:245-255

Published Date: 3 September 2015

Molecular targets in arthritis and recent trends in nanotherapy

Roy K, Kanwar RK, Kanwar JR

International Journal of Nanomedicine 2015, 10:5407-5420

Published Date: 26 August 2015

Is increasing the dose of Entecavir effective in partial virological responders?

Erturk A, Adnan Akdogan R, Parlak E, Cure E, Cumhur Cure M, Ozturk C

Drug Design, Development and Therapy 2014, 8:621-625

Published Date: 29 May 2014

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012