Non-viral Nanoparticle Delivers Small Interfering RNA to Macrophages in Vitro and in Vivo

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Mar 24

PMID 25799489

Citations 12

Authors

Mei Zhang

Yunxiang Gao

Kevin Caja

Bocheng Zhao

Julian A Kim

Affiliations

Soon will be listed here.

Abstract

Macrophages are increasingly being viewed as therapeutic target for various cancers and many inflammatory diseases. Sequence specific gene reduction by siRNA represents an attractive approach to modulate macrophage function. However, delivery of the therapeutic siRNA into macrophages by non-viral nanoparticles has been a major technical challenge. In this study, we developed a glucan-based siRNA carrier system (BG34-10-Re-I) and demonstrated that the BG34-10-Re-I can effectively assemble siRNA into uniformly distributed nanoparticles of the novel core-shell structure. The BG34-10-Re-I/siRNA nanoparticles effectively reduced gene expression of macrophage migration inhibitory factor (MIF) in primary macrophages at both protein and mRNA level. The nanoparticles also mediated a sustained reduction of MIF within primary macrophages. Moreover, systemic injection of the nanoparticles into the Balb/c mice bearing 4T1 mammary tumors resulted in the MIF reduction in tumor-associated macrophages. Mechanistic studies demonstrated that the glucan-shell and the siRNA-core structure contribute to the effective delivery of MIF siRNA to macrophages both in vitro and in vivo. This study represents the first development of the primary macrophage MIF gene targeted non-viral nanoparticle system for both in vitro and in vivo applications.

Citing Articles

Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review.

Zhao X, Amevor F, Xue X, Wang C, Cui Z, Dai S J Nanobiotechnology. 2023; 21(1):121.

PMID: 37029392 PMC: 10081370. DOI: 10.1186/s12951-023-01876-5.

Genome editing in cancer: Challenges and potential opportunities.

Breier D, Peer D Bioact Mater. 2022; 21:394-402.

PMID: 36185740 PMC: 9483578. DOI: 10.1016/j.bioactmat.2022.08.013.

Tumor-Associated Macrophages: Combination of Therapies, the Approach to Improve Cancer Treatment.

Moeini P, Niedzwiedzka-Rystwej P Int J Mol Sci. 2021; 22(13).

PMID: 34281293 PMC: 8269174. DOI: 10.3390/ijms22137239.

Progress in drug delivery system for fibrosis therapy.

Xing L, Chang X, Shen L, Zhang C, Fan Y, Cho C Asian J Pharm Sci. 2021; 16(1):47-61.

PMID: 33613729 PMC: 7878446. DOI: 10.1016/j.ajps.2020.06.005.

Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting.

Fiani M, Barreca V, Sargiacomo M, Ferrantelli F, Manfredi F, Federico M Int J Mol Sci. 2020; 21(17).

PMID: 32878276 PMC: 7503580. DOI: 10.3390/ijms21176318.

References

Courties G, Heidt T, Sebas M, Iwamoto Y, Jeon D, Truelove J . In vivo silencing of the transcription factor IRF5 reprograms the macrophage phenotype and improves infarct healing. J Am Coll Cardiol. 2013; 63(15):1556-66. PMC: 3992176. DOI: 10.1016/j.jacc.2013.11.023. View

Bach J, Rinn B, Meyer B, Dodel R, Bacher M . Role of MIF in inflammation and tumorigenesis. Oncology. 2008; 75(3-4):127-33. DOI: 10.1159/000155223. View

Barros M, Hauck F, Dreyer J, Kempkes B, Niedobitek G . Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages. PLoS One. 2013; 8(11):e80908. PMC: 3829941. DOI: 10.1371/journal.pone.0080908. View

Larson D, Horak K . Macrophage migration inhibitory factor: controller of systemic inflammation. Crit Care. 2006; 10(2):138. PMC: 1550887. DOI: 10.1186/cc4899. View

Price S . Connective tissue diseases: small-molecule inhibitor of mIF protects lupus-prone mice from kidney disease. Nat Rev Rheumatol. 2011; 7(2):70. DOI: 10.1038/nrrheum.2010.217. View

Zhang X, Edwards J, Mosser D . The expression of exogenous genes in macrophages: obstacles and opportunities. Methods Mol Biol. 2009; 531:123-43. PMC: 2821576. DOI: 10.1007/978-1-59745-396-7_9. View

Kambal A, Mitchell G, Cary W, Gruenloh W, Jung Y, Kalomoiris S . Generation of HIV-1 resistant and functional macrophages from hematopoietic stem cell-derived induced pluripotent stem cells. Mol Ther. 2010; 19(3):584-93. PMC: 3048185. DOI: 10.1038/mt.2010.269. View

Siveen K, Kuttan G . Role of macrophages in tumour progression. Immunol Lett. 2009; 123(2):97-102. DOI: 10.1016/j.imlet.2009.02.011. View

Pires L, Oliveira H, Barrias C, Sampaio P, Pereira A, Maiato H . Imidazole-grafted chitosan-mediated gene delivery: in vitro study on transfection, intracellular trafficking and degradation. Nanomedicine (Lond). 2011; 6(9):1499-512. DOI: 10.2217/nnm.11.51. View

10.

Love K, Mahon K, Levins C, Whitehead K, Querbes W, Dorkin J . Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci U S A. 2010; 107(5):1864-9. PMC: 2804742. DOI: 10.1073/pnas.0910603106. View

11.

Jokerst J, Lobovkina T, Zare R, Gambhir S . Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond). 2011; 6(4):715-28. PMC: 3217316. DOI: 10.2217/nnm.11.19. View

12.

Olefsky J, Glass C . Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010; 72:219-46. DOI: 10.1146/annurev-physiol-021909-135846. View

13.

Zhang M, Kim J . Effect of molecular size and modification pattern on the internalization of water soluble β-(1 → 3)-(1 → 4)-glucan by primary murine macrophages. Int J Biochem Cell Biol. 2012; 44(6):914-27. DOI: 10.1016/j.biocel.2012.02.018. View

14.

Basha G, Novobrantseva T, Rosin N, Tam Y, Hafez I, Wong M . Influence of cationic lipid composition on gene silencing properties of lipid nanoparticle formulations of siRNA in antigen-presenting cells. Mol Ther. 2011; 19(12):2186-200. PMC: 3242662. DOI: 10.1038/mt.2011.190. View

15.

Muta T . Molecular basis for invertebrate innate immune recognition of (1-->3)-beta-D-glucan as a pathogen-associated molecular pattern. Curr Pharm Des. 2006; 12(32):4155-61. DOI: 10.2174/138161206778743529. View

16.

Wilson R, Doudna J . Molecular mechanisms of RNA interference. Annu Rev Biophys. 2013; 42:217-39. PMC: 5895182. DOI: 10.1146/annurev-biophys-083012-130404. View

17.

Bloomfield V . DNA condensation by multivalent cations. Biopolymers. 1997; 44(3):269-82. DOI: 10.1002/(SICI)1097-0282(1997)44:3<269::AID-BIP6>3.0.CO;2-T. View

18.

Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y, Todo S . Macrophage migration inhibitory factor (MIF): Its potential role in tumor growth and tumor-associated angiogenesis. Ann N Y Acad Sci. 2003; 995:171-82. DOI: 10.1111/j.1749-6632.2003.tb03220.x. View

19.

Pecot C, Calin G, Coleman R, Lopez-Berestein G, Sood A . RNA interference in the clinic: challenges and future directions. Nat Rev Cancer. 2010; 11(1):59-67. PMC: 3199132. DOI: 10.1038/nrc2966. View

20.

Pelosi L, Imai T, Chanzy H, Heux L, Buhler E, Bulone V . Structural and morphological diversity of (1-->3)-beta-D-glucans synthesized in vitro by enzymes from Saprolegnia monoïca. Comparison with a corresponding in vitro product from blackberry (Rubus fruticosus). Biochemistry. 2003; 42(20):6264-74. DOI: 10.1021/bi0340550. View