Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling
Open accessAbstract
Despite efforts to understand the interactions between nanoparticles and cells, the cellular processes that determine the efficiency of intracellular drug delivery remain unclear. Here we examine cellular uptake of short interfering RNA (siRNA) delivered in lipid nanoparticles (LNPs) using cellular trafficking probes in combination with automated high-throughput confocal microscopy. We also employed defined perturbations of cellular pathways paired with systems biology approaches to uncover protein-protein and protein-small molecule interactions. We show that multiple cell signaling effectors are required for initial cellular entry of LNPs through macropinocytosis, including proton pumps, mTOR and cathepsins. siRNA delivery is substantially reduced as ≅70% of the internalized siRNA undergoes exocytosis through egress of LNPs from late endosomes/lysosomes. Niemann-Pick type C1 (NPC1) is shown to be an important regulator of the major recycling pathways of LNP-delivered siRNAs. NPC1-deficient cells show enhanced cellular retention of LNPs inside late endosomes and lysosomes, and increased gene silencing of the target gene. Our data suggest that siRNA delivery efficiency might be improved by designing delivery vehicles that can escape the recycling pathways.
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Only a small amount of lipid nanoparticles may be able to escape from the endosome.
“Indeed, only a small amount of lipid nanoparticles may be able to escape from the endosome137–139.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [137]
Following cellular internalization, lipid nanoparticles are usually trapped in endosomal compartments.
“Following cellular internalization, lipid nanoparticles are usually trapped in endosomal compartments137–139.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [137]
The transporter Niemann-Pick Type C-1 located on late endolysosomes is responsible for exocytosis of a large fraction of internalized (si)RNA LNPs, strongly reducing cytosolic delivery.
“For instance, the transporter Niemann-Pick Type C-1, located on late endolysomes, was found to be responsible for the exocytosis of a large fraction of internalized (si)RNA LNPs, hence strongly reducing the cytosolic delivery [121].”
From Three decades of messenger RNA vaccine development (2019) · cites this paper as [121]
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Cytoscape: A software Environment for integrated models of biomolecular interaction networks
Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., & Ideker, T. (2003) · Genome Research · doi:10.1101/gr.1239303 · Cited by 51,888 · see citing works
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456 · see citing works
Maere, S., Heymans, K., & Kuiper, M. (2005) · Bioinform. · doi:10.1093/bioinformatics/bti551 · Cited by 4,251 · see citing works
Knocking down barriers: advances in siRNA delivery
Whitehead, K. A., Langer, R., & Anderson, D. G. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2742 · Cited by 3,115 · see citing works
Self-citationDoherty, G. J., & McMahon, H. T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.081307.110540 · Cited by 3,075 · see citing works
Rab27a and Rab27b control different steps of the exosome secretion pathway
Ostrowski, M., Carmo, N., Krumeich, S., Fanget, I., Raposo, G., Savina, A., Moita, C. F., Schauer, K., Hume, A. N., Freitas, R. P., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb2000 · Cited by 2,761 · see citing works
Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
Davis, M. E., Zuckerman, J. E., Choi, C. H. J., Seligson, D. B., Tolcher, A. W., Alabi, C. A., Yen, Y., Heidel, J. D., & Ribas, A. (2010) · Nature · doi:10.1038/nature08956 · Cited by 2,508 · see citing works
Self-citationSahay, G., Alakhova, D. Y., & Kabanov, A. V. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.01.036 · Cited by 2,181 · see citing works
Self-citationRegulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., Garcı́a-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,726 · see citing works
Self-citationZoncu, R., Bar-Peled, L., Efeyan, A., Wang, S., Sancak, Y., & Sabatini, D. M. (2011) · Science · doi:10.1126/science.1207056 · Cited by 1,673 · see citing works
Self-citationCellular cholesterol trafficking and compartmentalization
Ikonen, E. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2336 · Cited by 1,455 · see citing works
Ebola virus entry requires the cholesterol transporter Niemann–Pick C1
Carette, J. E., Raaben, M., Wong, A., Herbert, A. S., Obernosterer, G., Mulherkar, N., Kuehne, A. I., Kranzusch, P. J., Griffin, A. M., Ruthel, G. T., et al. (2011) · Nature · doi:10.1038/nature10348 · Cited by 1,309 · see citing works
Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms
Akinc, A., Querbes, W., De, S., Qin, J., Frank-Kamenetsky, M., Jayaprakash, K. N., Jayaraman, M., Rajeev, K. G., Cantley, W. L., Dorkin, J. R., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.85 · Cited by 1,261 · see citing works
Uptake Pathways and Subsequent Intracellular Trafficking in Nonviral Gene Delivery
Khalil, I. A., Kogure, K., Akita, H., & Harashima, H. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.1.8 · Cited by 1,241 · see citing works
Chloride Accumulation and Swelling in Endosomes Enhances DNA Transfer by Polyamine-DNA Polyplexes
Sonawane, N. D., Szoka, F. C., & Verkman, A. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308643200 · Cited by 1,083 · see citing works
Gibbings, D., Ciaudo, C., Erhardt, M., & Voinnet, O. (2009) · Nature Cell Biology · doi:10.1038/ncb1929 · Cited by 990 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
Self-citationTherapeutic siRNA silencing in inflammatory monocytes in mice
Leuschner, F., Dutta, P., Gorbatov, R., Novobrantseva, T. I., Donahoe, J. S., Courties, G., Lee, K. M., Kim, J. I., Markmann, J. F., Marinelli, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1989 · Cited by 839 · see citing works
Self-citationStenmark, H., & Olkkonen, V. M. (2001) · Genome biology · doi:10.1186/gb-2001-2-5-reviews3007 · Cited by 714 · see citing works
More Effective Nanomedicines through Particle Design
Wang, J., Byrne, J. D., Napier, M. E., & DeSimone, J. M. (2011) · Small · doi:10.1002/smll.201100442 · Cited by 474 · see citing works
Systems survey of endocytosis by multiparametric image analysis
Collinet, C., Stöter, M., Bradshaw, C. R., Samusik, N., Rink, J. C., Kenski, D. M., Habermann, B. H., Buchholz, F., Henschel, R., Mueller, M., et al. (2010) · Nature · doi:10.1038/nature08779 · Cited by 446 · see citing works
Chen, D. L., Love, K. T., Chen, Y., Eltoukhy, A. A., Kastrup, C. J., Sahay, G., Jeon, A., Dong, Y., Whitehead, K. A., & Anderson, D. G. (2012) · Journal of the American Chemical Society · doi:10.1021/ja301621z · Cited by 422 · see citing works
Self-citationComplex Inhibitory Effects of Nitric Oxide on Autophagy
Sarkar, S., Korolchuk, V. I., Renna, M., Imarisio, S., Fleming, A., Williams, A. J., Garcı́a-Arencibia, M., Rose, C., Luo, S., Underwood, B. R., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.04.029 · Cited by 381 · see citing works
Self-citationNucleic Acid Delivery: The Missing Pieces of the Puzzle?
Nguyen, J., & Szoka, F. C. (2012) · Accounts of Chemical Research · doi:10.1021/ar3000162 · Cited by 347 · see citing works
Silencing by small RNAs is linked to endosomal trafficking
Lee, Y. S., Pressman, S., Andress, A. P., Kim, K., White, J. L., Cassidy, J. J., Li, X., Lubell, K., Lim, D., Cho, I. S., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1930 · Cited by 338 · see citing works
Bayer, N., Schober, D., Prchla, E., Murphy, R. F., Blaas, D., & Fuchs, R. (1998) · Journal of Virology · doi:10.1128/jvi.72.12.9645-9655.1998 · Cited by 329 · see citing works
Concanamycin A, the Specific Inhibitor of V-ATPases, Binds to the Vo Subunit c
Huss, M., Ingenhorst, G., König, S., Gaßel, M., Dröse, S., Zeeck, A., Altendorf, K., & Wieczorek, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207345200 · Cited by 278 · see citing works
Ko, D. C., Gordon, M. D., Jin, J. Y., & Scott, M. P. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.3.601 · Cited by 244 · see citing works
The rough endoplasmatic reticulum is a central nucleation site of siRNA‐mediated RNA silencing
Stalder, L., Heusermann, W., Sokol, L., Trojer, D., Wirz, J., Hean, J., Fritzsche, A., Aeschimann, F., Pfanzagl, V., Basselet, P., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.52 · Cited by 229 · see citing works
A Novel Mechanism Is Involved in Cationic Lipid-Mediated Functional siRNA Delivery
Lu, J. J.-Q., Langer, R., & Chen, J. (2009) · Molecular Pharmaceutics · doi:10.1021/mp900023v · Cited by 219 · see citing works
Self-citationCellular Uptake and Intracellular Trafficking of Antisense and siRNA Oligonucleotides
Juliano, R. L., Ming, X., & Nakagawa, O. (2011) · Bioconjugate Chemistry · doi:10.1021/bc200377d · Cited by 193 · see citing works
Basha, G., Novobrantseva, T. I., Rosin, N. L., Tam, Y. Y. C., Hafez, I. M., Wong, M., Sugo, T., Ruda, V. M., Qin, J., Klebanov, B., et al. (2011) · Molecular Therapy · doi:10.1038/mt.2011.190 · Cited by 182 · see citing works
Cessation of rapid late endosomal tubulovesicular trafficking in Niemann–Pick type C1 disease
Zhang, M., Dwyer, N. K., Love, D. C., Cooney, A. M., Comly, M., Neufeld, E. B., Pentchev, P. G., Blanchette‐Mackie, E. J., & Hanover, J. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081070898 · Cited by 143 · see citing works
Modulation of Cellular Cholesterol Transport and Homeostasis by Rab11
Hölttä‐Vuori, M., Tanhuanpää, K., Möbius, W., Somerharju, P. J., & Ikonen, E. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-01-0025 · Cited by 141 · see citing works
Rab8-dependent Recycling Promotes Endosomal Cholesterol Removal in Normal and Sphingolipidosis Cells
Linder, M. D., Uronen, R., Hölttä‐Vuori, M., van der Sluijs, P., Peränen, J., & Ikonen, E. (2006) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-07-0575 · Cited by 97 · see citing works
Endocytic Trafficking of Sphingomyelin Depends on Its Acyl Chain Length
Koivusalo, M., Jansen, M., Somerharju, P. J., & Ikonen, E. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-04-0330 · Cited by 76 · see citing works
Proof of concept for next-generation nanoparticle drugs in humans
Sheridan, C. (2012) · Nature Biotechnology · doi:10.1038/nbt0612-471 · Cited by 69 · see citing works
FRET-Labeled siRNA Probes for Tracking Assembly and Disassembly of siRNA Nanocomplexes
Alabi, C. A., Love, K. T., Sahay, G., Stutzman, T., Young, W. T., Langer, R., & Anderson, D. G. (2012) · ACS Nano · doi:10.1021/nn3013838 · Cited by 67 · see citing works
Self-citationLai, S. K., Hida, K., Chen, C., & Hanes, J. S. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.015 · Cited by 67 · see citing works
RISC hitches onto endosome trafficking
Siomi, H., & Siomi, M. C. (2009) · Nature Cell Biology · doi:10.1038/ncb0909-1049 · Cited by 51 · see citing works
Real‐time gene delivery vector tracking in the endo‐lysosomal pathway of live cells
Suh, J., An, Y., Tang, B. C., et al. (2011) · Microscopy Research and Technique · doi:10.1002/jemt.21113 · Cited by 32 · see citing works
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Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076 · see citing works
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- Authors
- Sahay, G., Querbes, W., Alabi, C., Eltoukhy, A., Sarkar, S., Zurenko, C., Karagiannis, E., Love, K., Chen, D., Zoncu, R., Buganim, Y., Schroeder, A., Langer, R., & Anderson, D. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Alnylam Pharmaceuticals (United States) (US)
- Massachusetts Institute of Technology (US)
- Whitehead Institute for Biomedical Research (US)
- Harvard–MIT Division of Health Sciences and Technology (US)
- Corresponding author
- Anderson, Daniel G
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2013-06-23
- Volume
- 31
- Issue
- 7
- Pages
- 653-658
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC3814166
- OpenAlex
- W1483024467
- Cited by
- 948
- References
- 41
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- FWCI
- 29.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- PMC
- Funders
- National Institutes of Health (4r37eb000244-34)
- National Heart, Lung, and Blood Institute (HHSN268201000045C)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000244, R37-EB000244)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- siRNA delivery, lipid nanoparticles, endocytic recycling, macropinocytosis, NPC1, late endosomes, lysosomes, exocytosis, mTOR, cathepsins, proton pump, cellular uptake, gene silencing, intracellular trafficking
- MeSH terms
- Niemann-Pick C1 Protein, Carrier Proteins, Endocytosis, Humans, Lipids, Membrane Glycoproteins, Signal Transduction, Gene Transfer Techniques, Microscopy, Confocal, Gene Silencing, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins, Metal Nanoparticles, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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