AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Nano Research Article
Article Link
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article

Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Chengxiang Zhang1,†, Xinfu Zhang1, ,§, Weiyu Zhao1,†,,, ,§, Chunxi Zeng1, Wenqing Li1, Bin Li1, Xiao Luo1, Junan Li2, Justin Jiang1, Binbin Deng3, David W. McComb3,4, Yizhou Dong1,5,6,7,8,9( )
Division of Pharmaceutics & Pharmaceutical Chemistry,College of Pharmacy, The Ohio State University,Columbus,OH 43210,USA;
College of Pharmacy,The Ohio State University,Columbus,OH 43210,USA;
Center for Electron Microscopy and Analysis,The Ohio State University,Columbus,OH 43212,USA;
Department of Materials Science and Engineering,The Ohio State University,Columbus,OH 43210,USA;
Department of Biomedical Engineering,The Ohio State University,Columbus,OH 43210,USA;
The Center for Clinical and Translational Science,The Ohio State University,Columbus,OH 43210,USA;
The Comprehensive Cancer Center,The Ohio State University,Columbus,OH 43210,USA;
Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University,Columbus,OH 43210,USA;
Department of Radiation Oncology,The Ohio State University,Columbus,OH 43210,USA;

† Present address: State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China

§ Chengxiang Zhang, Xinfu Zhang, and Weiyu Zhao contributed equally to this work.

Show Author Information

Graphical Abstract

Abstract

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane® and Lipusu® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

Keywords

paclitaxel amino lipid derived nanoparticlesmRNA therapeuticscombination therapytriple-negative breast cancer

Electronic Supplementary Material

Download File(s)
12274_2019_2308_MOESM1_ESM.pdf (1.9 MB)

References

1

Denkert, C.; Liedtke, C.; Tutt, A.; von Minckwitz, G. Molecular alterations in triple-negative breast cancer—The road to new treatment strategies. Lancet 2017, 389, 2430–2442.
Crossref Google Scholar
2

The National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer (Version I. 2018-March 20, 2018)[Online]. 2018; https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (accessed Jun 1, 2018).
3

Bianchini, G.; Balko, J. M.; Mayer, I. A.; Sanders, M. E.; Gianni, L. Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat. Rev. Clin. Oncol. 2016, 13, 674–690.
Crossref Google Scholar
4

Mehta, R. S.; Barlow, W. E.; Albain, K. S.; Vandenberg, T. A.; Dakhil, S. R.; Tirumali, N. R.; Lew, D. L.; Hayes, D. F.; Gralow, J. R.; Livingston, R. B. et al. Combination anastrozole and fulvestrant in metastatic breast cancer. N. Engl. J. Med. 2012, 367, 435–444.
Crossref Google Scholar
5

Gandhi, L.; Rodríguez-Abreu, D.; Gadgeel, S.; Esteban, E.; Felip, E.; De Angelis, F.; Domine, M.; Clingan, P.; Hochmair, M. J.; Powell, S. F. et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N. Engl. J. Med. 2018, 378, 2078–2092.
Crossref Google Scholar
6

Schmid, P.; Park, Y. H.; Muñoz-Couselo, E.; Kim, S. B.; Sohn, J.; Im, S. A.; Holgado, E.; Wang, Y.; Dang, T.; Aktan, G. et al. Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): Preliminary results from KEYNOTE-173. J. Clin. Oncol. 2017, 35, 556–556.
Crossref Google Scholar
7

Wang, Y. W.; Sun S. Y.; Zhang, Z. Y.; Shi D. L. Nanomaterials for cancer precision medicine. Adv. Mater. 2018, 30, 1705660.
Crossref Google Scholar
8

Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012, 490, 61–70.
Crossref Google Scholar
9

Morris, L. G. T.; Chan, T. A. Therapeutic targeting of tumor suppressor genes. Cancer 2015, 121, 1357–1368.
Crossref Google Scholar
10

Bae, Y. H.; Shin, J. M.; Park, H. J.; Jang, H. O.; Bae, M. K.; Bae, S. K. Gain-of-function mutant p53-R280K mediates survival of breast cancer cells. Genes Genomics 2014, 36, 171–178.
Crossref Google Scholar
11

Sahin, U.; Karikó, K.; Türeci, Ö. mRNA-based therapeutics—Developing a new class of drugs. Nat. Rev. Drug Discov. 2014, 13, 759–780.
Crossref Google Scholar
12

Weissman, D. mRNA transcript therapy. Expert Rev. Vaccines 2015, 14, 265–281.
Crossref Google Scholar
13

Yamamoto, A.; Kormann, M.; Rosenecker, J.; Rudolph, C. Current prospects for mRNA gene delivery. Eur. J. Pharm. Biopharm. 2009, 71, 484–489.
Crossref Google Scholar
14

Islam, M. A.; Reesor, E. K. G.; Xu, Y. J.; Zope, H. R.; Zetter, B. R.; Shi, J. J. Biomaterials for mRNA delivery. Biomater. Sci. 2015, 3, 1519–1533.
Crossref Google Scholar
15

Guan, S.; Rosenecker, J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017, 24, 133–143.
Crossref Google Scholar
16

Hajj, K. A.; Whitehead, K. A. Tools for translation: Non-viral materials for therapeutic mRNA delivery. Nat. Rev. Mater. 2017, 2, 17056.
Crossref Google Scholar
17

Li, B.; Zhang, X. F.; Dong, Y. Z. Nanoscale platforms for messenger RNA delivery. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2018, e1530.
Crossref Google Scholar
18

Liu, L. N.; Wang, Y. H.; Miao, L.; Liu, Q.; Musetti, S.; Li, J.; Huang, L. Combination immunotherapy of MUC1 mRNA nano-vaccine and CTLA-4 blockade effectively inhibits growth of triple negative breast cancer. Mol. Ther. 2018, 26, 45–55.
Crossref Google Scholar
19

Islam, M. A.; Xu, Y. J.; Tao, W.; Ubellacker, J. M.; Lim, M.; Aum, D.; Lee, G. Y.; Zhou, K.; Zope, H.; Yu, M. et al. Restoration of tumour-growth suppression in vivo via systemic nanoparticle-mediated delivery of PTEN mRNA. Nat. Biomed. Eng. 2018, 2, 850–864.
Crossref Google Scholar
20

Haabeth, O. A. W.; Blake, T. R.; McKinlay, C. J.; Waymouth, R. M.; Wender, P. A.; Levy, R. mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice. Proc. Natl. Acad. Sci. USA 2018, 115, E9153–E9161.
Crossref Google Scholar
21

Van Hoecke, L.; Van Lint, S.; Roose, K.; Van Parys, A.; Vandenabeele, P.; Grooten, J.; Tavernier, J.; De Koker, S.; Saelens, X. Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes. Nat. Commun. 2018, 9, 3417.
Crossref Google Scholar
22

Kranz, L. M.; Diken, M.; Haas, H.; Kreiter, S.; Loquai, C.; Reuter, K. C.; Meng, M.; Fritz, D.; Vascotto, F.; Hefesha, H. et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 2016, 534, 396–401.
Crossref Google Scholar
23

Oberli, M. A.; Reichmuth, A. M.; Dorkin, J. R.; Mitchell, M. J.; Fenton, O. S.; Jaklenec, A.; Anderson, D. G.; Langer, R.; Blankschtein, D. Lipid nanoparticle assisted mRNA delivery for potent cancer immunotherapy. Nano Lett. 2017, 17, 1326–1335.
Crossref Google Scholar
24

Cheng, Q.; Wei, T.; Jia, Y. M.; Farbiak, L.; Zhou, K. J.; Zhang, S. Y.; Wei, Y. L.; Zhu, H.; Siegwart, D. J. Dendrimer-based lipid nanoparticles deliver therapeutic FAH mRNA to normalize liver function and extend survival in a mouse model of hepatorenal tyrosinemia type I. Adv. Mater. 2018, 30, 1805308.
Crossref Google Scholar
25

Miller, J. B.; Zhang, S. Y.; Kos, P.; Xiong, H.; Zhou, K. J.; Perelman, S. S.; Zhu, H.; Siegwart, D. J. Non-Viral CRISPR/Cas gene editing in vitro and in vivo enabled by synthetic nanoparticle co-delivery of Cas9 mRNA and sgRNA. Angew. Chem., Int. Ed. 2017, 56, 1059–1063.
Crossref Google Scholar
26

Robinson, E.; MacDonald, K. D.; Slaughter, K.; McKinney, M.; Patel, S.; Sun, C.; Sahay, G. Lipid nanoparticle-delivered chemically modified mRNA Restores chloride secretion in cystic fibrosis. Mol. Ther. 2018, 26, 2034–2046.
Crossref Google Scholar
27

Gurnani, M.; Lipari, P.; Dell, J.; Shi, B.; Nielsen, L. L. Adenovirus- mediated p53 gene therapy has greater efficacy when combined with chemotherapy against human head and neck, ovarian, prostate, and breast cancer. Cancer Chemother. Pharmacol. 1999, 44, 143–151.
Crossref Google Scholar
28

Jiang, C.; Mei, M.; Li, B.; Zhu, X. R.; Zu, W. H.; Tian, Y. J.; Wang, Q. N.; Guo, Y.; Dong, Y. Z.; Tan, X. A non-viral CRISPR/Cas9 delivery system for therapeutically targeting HBV DNA and pcsk9 in vivo. Cell Res. 2017, 27, 440–443.
Crossref Google Scholar
29

Jia, L. Nanoparticle formulation increases oral bioavailability of poorly soluble drugs: Approaches, experimental evidences and theory. Curr. Nanosci. 2005, 1, 237–243.
Crossref Google Scholar
30

Doane, T.; Burda, C. Nanoparticle mediated non-covalent drug delivery. Adv. Drug Deliv. Rev. 2013, 65, 607–621.
Crossref Google Scholar
31

Sofias, A. M.; Dunne, M.; Storm, G.; Allen, C. The battle of "nano" paclitaxel. Adv. Drug Deliv. Rev. 2017, 122, 20–30.
Crossref Google Scholar
32

Ye, L.; He, J.; Hu, Z. P.; Dong, Q. J.; Wang, H. B.; Fu, F. H.; Tian, J. W. Antitumor effect and toxicity of Lipusu in rat ovarian cancer xenografts. Food Chem. Toxicol. 2013, 52, 200–206.
Crossref Google Scholar
33

Oudin, M. J.; Barbier, L.; Schäfer, C.; Kosciuk, T.; Miller, M. A.; Han, S.; Jonas, O.; Lauffenburger, D. A.; Gertler, F. B. MENA confers resistance to paclitaxel in triple-negative breast cancer. Mol. Cancer Ther. 2017, 16, 143–155.
Crossref Google Scholar
34

Conley, S. J.; Baker, T. L.; Burnett, J. P.; Theisen, R. L.; Lazarus, D.; Peters, C. G.; Clouthier, S. G.; Eliasof, S.; Wicha, M. S. CRLX101, an investigational camptothecin-containing nanoparticle-drug conjugate, targets cancer stem cells and impedes resistance to antiangiogenic therapy in mouse models of breast cancer. Breast Cancer Res. Treat. 2015, 150, 559–567.
Crossref Google Scholar
35

Li, B.; Luo, X.; Deng, B. B.; Wang, J. F.; McComb, D. W.; Shi, Y. M.; Gaensler, K. M. L.; Tan, X.; Dunn, A. L.; Kerlin, B. A. et al. An Orthogonal array optimization of lipid-like nanoparticles for mRNA delivery in vivo. Nano Lett. 2015, 15, 8099–8107.
Crossref Google Scholar
36

Zhang, X. F.; Li, B.; Luo, X.; Zhao, W. Y.; Jiang, J.; Zhang, C. X.; Gao, M.; Chen, X. F.; Dong, Y. Z. Biodegradable amino-ester nanomaterials for Cas9 mRNA delivery in vitro and in vivo. ACS Appl. Mater. Interfaces 2017, 9, 25481–25487.
Crossref Google Scholar
37

Li, B.; Luo, X.; Deng, B. B.; Giancola, J. B.; McComb, D. W.; Schmittgen, T. D.; Dong, Y. Z. Effects of local structural transformation of lipid-like compounds on delivery of messenger RNA. Sci. Rep. 2016, 6, 22137.
Crossref Google Scholar
38

Muller, P. A. J.; Vousden, K. H. Mutant p53 in cancer: New functions and therapeutic opportunities. Cancer Cell 2014, 25, 304–317.
Crossref Google Scholar
39

Weiss, R. B.; Donehower, R. C.; Wiernik, P. H.; Ohnuma, T.; Gralla, R. J.; Trump, D. L.; Baker, J. R. B. Jr.; Van Echo, D. A.; Von Hoff, D. D.; Leyland-Jones, B. Hypersensitivity reactions from taxol. J. Clin. Oncol. 1990, 8, 1263–1268.
Crossref Google Scholar
40

Balaji, B. S.; Lewis, M. R. Double exponential growth of aliphatic polyamide dendrimers via AB2 hypermonomer strategy. Chem. Commun. (Camb. ) 2009, 4593–4595.
Crossref Google Scholar
41

Gjoerup, O.; Zaveri, D.; Roberts, T. M. Induction of p53-independent apoptosis by simian virus 40 small t antigen. J. Virol. 2001, 75, 9142– 9155.
Crossref Google Scholar
42

Kauffman, K. J.; Dorkin, J. R.; Yang, J. H.; Heartlein, M. W.; DeRosa, F.; Mir, F. F.; Fenton, O. S.; Anderson, D. G. Optimization of lipid nanoparticle formulations for mRNA Delivery in vivo with fractional factorial and definitive screening designs. Nano Lett. 2015, 15, 7300–7306.
Crossref Google Scholar
Nano Research
Volume 12 Issue 4,
April 2019
Pages 855-861
DOI: 10.1007/s12274-019-2308-9
Cite this article:
Zhang C, Zhang X, Zhao W, et al. Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer. Nano Research, 2019, 12(4): 855-861. https://doi.org/10.1007/s12274-019-2308-9
Topics:
Chemotherapy DiagnosisDiseasesGenesNanoparticlesProteinsSignal encodingTumors

894

Views

43

Crossref

N/A

Web of Science

45

Scopus

0

CSCD

Altmetrics
Received: 28 December 2018
Revised: 17 January 2019
Accepted: 20 January 2019
Published: 01 February 2019
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019
Return