Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy
Abstract
Repolarizing Tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages with microRNA (miR) is a plausible approach for cancer treatment. However, how to achieve TAM-targeted miR delivery remains a challenge. The present study generated redox/pH dual-responsive hybrid polypeptide nanovectors, which consisted of self-crosslinked redox-responsive nanoparticles based on galactose-functionalized n-butylamine-poly(l-lysine)-b-poly(l-cysteine) polypeptides (GLC) coated with DCA-grafted sheddable PEG-PLL (sPEG) copolymers. The ex vivo study showed that sPEG shielded cationic GLC core at physiological pH but quickly shed off to re-expose GLC due to it charge reversible property. Encapsulation with sPEG/GLC nanovectors effectively facilitated macrophage-targeted miR delivery at the acidic condition but diminished miR uptake at neutral pH. Administration of miR155-loaded sPEG/GLC (sPEG/GLC/155) nanocomplexes increased miR155 expression in TAMs about 100-400 folds both in vitro and in vivo. sPEG/GLC/155 also effectively repolarized immunosuppressive TAMs to anti-tumor M1 macrophages through elevating M1 macrophage markers (IL-12, iNOS, MHC II) and suppressing M2 macrophage markers (Msr2 and Arg1) in TAMs. Moreover, the treatment of sPEG/GLC/155 significantly increased activated T lymphocytes and NK cells in tumors, which consequently led to robust tumor regression. Hence, TAM-targeted delivery of miR with redox/pH dual-responsive sPEG/GLC nanovectors could be a promising approach to re-polarize TAMs to M1 macrophages in situ and induce tumor regression.
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Extensive efforts on facilitating particle accumulation in targeted tissues for non-viral delivery vectors-mediated gene therapy exist.
“In the past decades, there have been extensive efforts on facilitating particles accumulation in the targeted tissues for non-viral delivery vectors-mediated gene therapy [155, 156].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [155]
Cites
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,208 · see citing works
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190 · see citing works
Non-viral vectors for gene-based therapy
Yin, H., Kanasty, R. L., Eltoukhy, A. A., Vegas, A. J., Dorkin, J. R., & Anderson, D. G. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3763 · Cited by 3,123 · see citing works
Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis
Condeelis, J. S., & Pollard, J. W. (2006) · Cell · doi:10.1016/j.cell.2006.01.007 · Cited by 2,693 · see citing works
He, C., Hu, Y., Yin, L., Tang, C., & Yin, C. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.01.065 · Cited by 2,607 · see citing works
Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment
Chanmee, T., Ontong, P., Konno, K., & Itano, N. (2014) · Cancers · doi:10.3390/cancers6031670 · Cited by 1,537 · see citing works
THE INTERLEUKIN-12/INTERLEUKIN-12-RECEPTOR SYSTEM: Role in Normal and Pathologic Immune Responses
Gately, M. K., Renzetti, L. M., Magram, J., STERN, A. S., Adorini, L., Gubler, U., & Presky, D. H. (1998) · Annual Review of Immunology · doi:10.1146/annurev.immunol.16.1.495 · Cited by 1,231 · see citing works
Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation
Salomon, B. L., & Bluestone, J. A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.225 · Cited by 1,005 · see citing works
RNAi therapeutics: Principles, prospects and challenges
Aagaard, L., & Rossi, J. J. (2007) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.03.005 · Cited by 895 · see citing works
Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids
Heyes, J., Palmer, L., Bremner, K., & MacLachlan, I. (2005) · Journal of Controlled Release · doi:10.1016/j.jconrel.2005.06.014 · Cited by 572 · see citing works
The preparation of N-carboxyanhydrides of α-amino acids using bis(trichloromethyl)carbonate
Daly, W. H., & Poché, D. S. (1988) · Tetrahedron Letters · doi:10.1016/s0040-4039(00)82209-1 · Cited by 556 · see citing works
Kedmi, R., Ben-Arie, N., & Peer, D. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.05.027 · Cited by 546 · see citing works
Cytokines as biomarkers of nanoparticle immunotoxicity
Elsabahy, M., & Wooley, K. L. (2013) · Chemical Society Reviews · doi:10.1039/c3cs60064e · Cited by 408 · see citing works
Gandhi, N. S., Tekade, R. K., & Chougule, M. B. (2014) · Journal of Controlled Release · doi:10.1016/j.jconrel.2014.09.001 · Cited by 397 · see citing works
Tumor-associated macrophages: Effectors of angiogenesis and tumor progression
Coffelt, S. B., Hughes, R., & Lewis, C. E. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.02.004 · Cited by 350 · see citing works
Tumour macrophages as potential targets of bisphosphonates
Rogers, T. L., & Holen, I. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-177 · Cited by 329 · see citing works
Allavena, P., Signorelli, M., Chieppa, M., Erba, E., Bianchi, G., Marchesi, F., Olimpio, C. O., Bonardi, C., Garbi, A., Lissoni, A. A., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4037 · Cited by 286 · see citing works
Anti‐tumour strategies aiming to target tumour‐associated macrophages
Tang, X., Mo, C., Wang, Y., Wei, D., & Xiao, H. (2012) · Immunology · doi:10.1111/imm.12023 · Cited by 278 · see citing works
Watkins, S. K., Egilmez, N. K., Suttles, J., & Stout, R. D. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.3.1357 · Cited by 273 · see citing works
Re-polarization of tumor-associated macrophages to pro-inflammatory M1 macrophages by microRNA-155
Cai, X. F., Yin, Y., Li, N., Zhu, D., Zhang, J., Zhang, C., & Zen, K. (2012) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjs044 · Cited by 260 · see citing works
Zhu, S., Niu, M., O’Mary, H. L., & Cui, Z. (2013) · Molecular Pharmaceutics · doi:10.1021/mp400216r · Cited by 233 · see citing works
He, Y., Cheng, G., Li, X., Nie, Y., He, B., & Gu, Z. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.09.049 · Cited by 216 · see citing works
Zheng, C., Zheng, M., Gong, P., Deng, J., Yi, H., Zhang, P., Zhang, Y., Liu, P., Ma, Y., & Cai, L. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.01.053 · Cited by 200 · see citing works
Self-citationHe, M. Y., Xu, Z., Ding, T., Kuang, D., & Zheng, L. (2009) · Cellular and Molecular Immunology · doi:10.1038/cmi.2009.45 · Cited by 199 · see citing works
Targeted delivery of oligonucleotides into tumor-associated macrophages for cancer immunotherapy
Huang, Z. D., Zhang, Z., Jiang, Y., Zhang, D., Chen, J., Dong, L., & Zhang, J. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.11.013 · Cited by 169 · see citing works
Eubank, T. D., Roberts, R. D., Khan, M., Curry, J. M., Nuovo, G. J., Kuppusamy, P., & Marsh, C. B. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-1405 · Cited by 166 · see citing works
Pan, H., Liu, L., & Cai, L. (2022) · Biomaterial engineering · doi:10.1007/978-981-16-5419-0_18 · Cited by 165 · see citing works
Self-citationThe C-type lectin MGL expressed by dendritic cells detects glycan changes on MUC1 in colon carcinoma
Saeland, E., van Vliet, S. J., Bäckström, M., van den Berg, V. C. M., Geijtenbeek, T. B. H., Meijer, G. A., & van Kooyk, Y. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-006-0274-z · Cited by 150 · see citing works
Nuclear Factor-κB and Tumor-Associated Macrophages
Mancino, A., & Lawrence, T. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1015 · Cited by 147 · see citing works
Cubillos‐Ruiz, J. R., Baird, J. R., Tesone, A. J., Rutkowski, M. R., Scarlett, U. K., Camposeco-Jacobs, A. L., Anadon-Arnillas, J., Harwood, N. M., Korc, M., Fiering, S., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3160 · Cited by 145 · see citing works
Luo, Z., Wang, C., Yi, H., et al. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.10.050 · Cited by 138 · see citing works
Self-citationMicroRNAs in cancer biology and therapy: Current status and perspectives
Price, C. O., & Chen, J. (2014) · Genes & Diseases · doi:10.1016/j.gendis.2014.06.004 · Cited by 137 · see citing works
The multiple roles of microRNA-155 in oncogenesis
Higgs, G., & Slack, F. (2013) · Journal of Clinical Bioinformatics · doi:10.1186/2043-9113-3-17 · Cited by 137 · see citing works
Nagai, T., Tanaka, M., Tsuneyoshi, Y., et al. (2009) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-009-0667-x · Cited by 126 · see citing works
Targeting of macrophage galactose‐type C ‐type lectin ( MGL ) induces DC signaling and activation
Napoletano, C., Zizzari, I. G., Rughetti, A., et al. (2012) · European Journal of Immunology · doi:10.1002/eji.201142086 · Cited by 109 · see citing works
Manthey, C. L., Johnson, D. L., Illig, C. R., Tuman, R. W., Zhao, Z., Baker, J. F., Chaikin, M. A., Donatelli, R. R., Franks, C. F., Zeng, L., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-09-0255 · Cited by 109 · see citing works
Immunotoxicity of Nanoparticles
Petrarca, C., Mangifesta, R., & Giampaolo, L. D. (2020) · Current topics in environmental health and preventive medicine · doi:10.1007/978-981-15-4735-5_6 · Cited by 97 · see citing works
Shiri, S., Alizadeh, A. M., Baradaran, B., Farhanghi, B., Shanehbandi, D., Khodayari, S., Khodayari, H., & Tavasoli, A. (2015) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2015.16.9.3917 · Cited by 92 · see citing works
Local targets for immune therapy to cancer: Tumor draining lymph nodes and tumor microenvironment
Fransen, M. F., Arens, R., & Melief, C. J. M. (2012) · International Journal of Cancer · doi:10.1002/ijc.27755 · Cited by 85 · see citing works
Soualhine, H., Deghmane, A., Sun, J., et al. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.179.8.5137 · Cited by 58 · see citing works
Lind, E. F., Millar, D. G., Dissanayake, D., Savage, J. C., Grimshaw, N., Kerr, W. G., & Ohashi, P. S. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1302941 · Cited by 54 · see citing works
Yi, H., Liu, L., Sheng, N., et al. (2016) · Biomacromolecules · doi:10.1021/acs.biomac.6b00141 · Cited by 45 · see citing works
Self-citationLiu, L., Yi, H., Wang, C., He, H., Li, P., Pan, H., Sheng, N., Ji, M., Cai, L., & Ma, Y. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1600182 · Cited by 45 · see citing works
Self-citationYi, H., Liu, P., Sheng, N., et al. (2016) · Nanoscale · doi:10.1039/c5nr07348k · Cited by 44 · see citing works
Self-citationScarano, A., Piattelli, A., Assenza, B., et al. (2011) · International Journal of Immunopathology and Pharmacology · doi:10.1177/03946320110240s212 · Cited by 32 · see citing works
Chèvre, R., Bihan, O. L., Beilvert, F., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq922 · Cited by 27 · see citing works
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Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities
Li, L., Hu, S., & Chen, X. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.04.031 · Cited by 415 · see citing works
Sun, Y., Zhao, Y., Zhao, X., Lee, R. J., Teng, L., & Zhou, C. (2017) · Molecules · doi:10.3390/molecules22101724 · Cited by 56 · see citing works
Li, J., Wang, J., Zhang, X., Xia, X., & Zhang, C. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.09.085 · Cited by 17 · see citing works
- Authors
- Liu, L., Yi, H., He, H., Pan, H., Cai, L., & Ma, Y.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Cai, Lintao
- Ma, Yifan
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 134
- Pages
- 166-179
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2608151576
- Cited by
- 124
- References
- 46
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 14 · 2021: 30 · 2020: 18 · 2019: 16 · 2018: 16 · 2017: 1
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81371679, 31571013, 21375141, 81401509, 81501580)
- Key International S&T Cooperation Project (2015DFH50230)
- Instrument Developing Project of CAS (YZ201439)
- Guangdong Natural Science Foundation of Research Team (2016A030312006)
- Shenzhen Science and Technology Program (KQCX20140521115045447, JCYJ20150401145529015, JCYJ20130402092657771, JSGG20160331185422390, JCYJ20150521094519473, JCYJ20160429191503002)
- SIAT Innovation Program for Excellent Young Researchers (201506)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- tumor-associated macrophages, macrophage repolarization, M1 macrophages, microRNA delivery, miR-155, redox-responsive nanoparticles, pH-responsive nanoparticles, dual-responsive drug delivery, cancer immunotherapy, tumor regression
- MeSH terms
- RAW 264.7 Cells, Animals, Electrophoresis, Agar Gel, Female, Killer Cells, Natural, Melanoma, Melanoma, Experimental, Mice, Inbred C57BL, Mice, Nude, Magnetic Resonance Spectroscopy, Peptides, T-Lymphocytes, Signal Transduction, Interleukin-12, MicroRNAs, Mice, Nitric Oxide Synthase Type II, Nanoparticles
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