Reconstructed apoptotic bodies as targeted "nano decoys" to treat intracellular bacterial infections within macrophages and cancer cells
Open accessAbstract
Abstract Staphylococcus aureus (S. aureus) is a highly pathogenic facultative anaerobe that in some instances resides as an intracellular bacterium within macrophages and cancer cells. This pathogen can establish secondary infection foci, resulting in recurrent systemic infections that are difficult to treat using systemic antibiotics. Here, we use reconstructed apoptotic bodies (ReApoBds) derived from cancer cells as “nano decoys” to deliver vancomycin intracellularly to kill S. aureus by targeting inherent “eat me” signaling of ApoBds. We prepared ReApoBds from different cancer cells (SKBR3, MDA-MB-231, HepG2, U87-MG, and LN229) and used them for vancomycin delivery. Physicochemical characterization showed ReApoBds size ranges from 80 to 150 nm and vancomycin encapsulation efficiency of 60 ± 2.56%. We demonstrate that the loaded vancomycin was able to kill intracellular S. aureus efficiently in an in vitro model of S. aureus infected RAW-264.7 macrophage cells, and U87-MG (p53-wt) and LN229 (p53-mt) cancer cells, compared to free-vancomycin treatment (P < 0.001). The vancomycin loaded ReApoBds treatment in S. aureus infected macrophages showed a two-log-order higher CFU reduction than the free-vancomycin treatment group. In vivo studies revealed that ReApoBds can specifically target macrophages and cancer cells. Vancomycin loaded ReApoBds have the potential to kill intracellular S. aureus infection in vivo in macrophages and cancer cells.
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Intracellular bacterial reservoirs within host cells pose a critical challenge in osteomyelitis by facilitating immune evasion and reducing antibiotic clearance, contributing to recurrence of refractory infections.
“Beyond biofilm formation, intracellular bacterial reservoirs within host cells pose a critical challenge in osteomyelitis by facilitating immune evasion and reducing antibiotic clearance, thereby contributing to the recurrence of refractory infections [40].”
From Nanocatalytic magnesium osteoimplants with biodegradable self-adaptive interfaces for therapeutic repair of infected bone defects (2026) · cites this paper as [40]
The Abstract (page not provided) says that intracellular S. aureus reservoirs can evade host defenses and seed recurrent infections. The Results and Discussion section (page not provided) says intracellular persistence may circumvent vancomycin treatment. The paper does not establish these effects specifically in osteomyelitis or link them to recurrent refractory bone infections. (LLM, conf=0.88)
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Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · see citing works
Protective and pathogenic functions of macrophage subsets
Murray, P. J., & Wynn, T. A. (2011) · Nature Reviews Immunology · doi:10.1038/nri3073 · Cited by 5,269 · see citing works
Tong, S. Y. C., Davis, J. S., Eichenberger, E., Holland, T. L., & Fowler, V. G. (2015) · Clinical Microbiology Reviews · doi:10.1128/cmr.00134-14 · Cited by 5,192 · see citing works
Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection
Zernecke, A., Bidzhekov, K., Noels, H., Shagdarsuren, E., Gan, L., Denecke, B., Hristov, M., Koeppel, T. A., Nazari-Jahantigh, M., Lutgens, E., et al. (2009) · Science Signaling · doi:10.1126/scisignal.2000610 · Cited by 1,335 · see citing works
Changes in prevalence of health care-associated infections in U.S. hospitals
Magill, S. S., O’Leary, E., Janelle, S. J., Thompson, D. L., Dumyati, G., Nadle, J., Wilson, L. E., Kainer, M. A., Lynfield, R., Greissman, S., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1801550 · Cited by 1,249 · see citing works
Apoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223 · see citing works
Health care-associated infections – an overview
Haque, M., Sartelli, M., McKimm, J., & Bakar, M. A. (2018) · Infection and Drug Resistance · doi:10.2147/idr.s177247 · Cited by 1,207 · see citing works
Novel antibody-antibiotic conjugate eliminates intracellular S. aureus
Lehar, S. M., Pillow, T., Xu, M., Staben, L., Kajihara, K. K., Vandlen, R., DePalatis, L., Raab, H., Hazenbos, W. L., Hiroshi Morisaki, J., et al. (2015) · Nature · doi:10.1038/nature16057 · Cited by 838 · see citing works
Nunes, A. S., Barros, A. S., Costa, E. C., Moreira, A. F., & Correia, I. J. (2019) · Biotechnology and Bioengineering · doi:10.1002/bit.26845 · Cited by 721 · see citing works
Zheng, J. H., Nguyen, V. H., Jiang, S.-N., Park, S.-H., Tan, W., Hong, S. H., Shin, M. G., Chung, I.-J., Hong, Y., Bom, H.-S., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aak9537 · Cited by 588 · see citing works
Caspase-mediated cleavage of phospholipid flippase for apoptotic phosphatidylserine exposure
Segawa, K., Kurata, S., Yanagihashi, Y., Brummelkamp, T. R., Matsuda, F., & Nagata, S. (2014) · Science · doi:10.1126/science.1252809 · Cited by 528 · see citing works
How macrophages deal with death
Lemke, G. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0167-y · Cited by 437 · see citing works
Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy
Hussain, S., Joo, J., Kang, J., Kim, B., Braun, G. B., She, Z.-G., Kim, D., Mann, A. P., Mölder, T., Teesalu, T., et al. (2018) · Nature Biomedical Engineering · doi:10.1038/s41551-017-0187-5 · Cited by 399 · see citing works
Intracellular staphylococcus aureus: Live-in and let die
Fraunholz, M. J., & Sinha, B. N. M. (2012) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2012.00043 · Cited by 380 · see citing works
A novel community driven software for functional enrichment analysis of extracellular vesicles data
Pathan, M., Keerthikumar, S., Chisanga, D., Alessandro, R., Ang, C., Askenase, P. W., Batagov, A. O., Benito‐Martín, A., Camussi, G., Clayton, A., et al. (2017) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2017.1321455 · Cited by 346 · see citing works
Infections in Cancer Patients with Solid Tumors: A Review
Rolston, K. V. I. (2017) · Infectious Diseases and Therapy · doi:10.1007/s40121-017-0146-1 · Cited by 335 · see citing works
Pavlyukov, M. S., Yu, H., Bastola, S., Minata, M., Shender, V. О., Lee, Y., Zhang, S., Wang, J., Komarova, S. V., Wang, J., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.012 · Cited by 321 · see citing works
Revisiting Mouse Peritoneal Macrophages: Heterogeneity, Development, and Function
Cassado, A. D. A., D’Império Lima, M. R., & Bortoluci, K. R. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00225 · Cited by 315 · see citing works
Identification and treatment of the Staphylococcus aureus reservoir in vivo
Surewaard, B. G. J., Deniset, J., Zemp, F. J., Amrein, M., Otto, M. J., Conly, J. M., Omri, A., Yates, R. M., & Kubes, P. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20160334 · Cited by 257 · see citing works
Where does a Staphylococcus aureus vaccine stand?
Fowler, V. G., & Proctor, R. A. (2014) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12570 · Cited by 241 · see citing works
Delivery systems to increase the selectivity of antibiotics in phagocytic cells
Briones, E., Colino, C. I., & Lanao, J. M. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.10.027 · Cited by 226 · see citing works
Bose, R. J., Sukumar, U. K., Zeng, Y., Afjei, R., Robinson, E. R., Lau, K. H., Bermudez, A., Habte, F. G., Pitteri, S. J., Sinclair, R., et al. (2018) · ACS Nano · doi:10.1021/acsnano.8b02587 · Cited by 224 · see citing works
Self-citationDisassembly of the Dying: Mechanisms and Functions
Atkin‐Smith, G. K., & Poon, I. K. H. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.08.011 · Cited by 214 · see citing works
Cain, D. W., O’Koren, E. G., Kan, M. J., Womble, M. A., Sempowski, G. D., Hopper, K., Gunn, M. D., & Kelsoe, G. H. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1300581 · Cited by 187 · see citing works
Extracellular vesicles induce minimal hepatotoxicity and immunogenicity
Saleh, A. F. A., Lázaro‐Ibáñez, E., Forsgard, M., Shatnyeva, O., Osteikoetxea, X., Karlsson, F. H., Heath, N., Ingelsten, M., Rose, J., Harris, J., et al. (2019) · Nanoscale · doi:10.1039/c8nr08720b · Cited by 185 · see citing works
Cell membrane-coated nanocarriers: the emerging targeted delivery system for cancer theranostics
Bose, R. J., Paulmurugan, R., Moon, J. J., Lee, S., & Park, H. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.02.001 · Cited by 154 · see citing works
Self-citationDBToolkit: processing protein databases for peptide-centric proteomics
Martens, L., Vandekerckhove, J., & Gevaert, K. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti588 · Cited by 140 · see citing works
Ercoli, G., Fernandes, V. E., Chung, W. Y., Wanford, J. J., Thomson, S., Bayliss, C. D., Straatman, K. R., Crocker, P. R., Dennison, A. R., Martínez‐Pomares, L., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0147-1 · Cited by 138 · see citing works
Zhang, J., Li, Q., Wu, Y., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0328-4 · Cited by 129 · see citing works
Zhang, X., Angsantikul, P., Man, Y. M., Zhuang, J., Zhang, Q., Wei, X., Jiang, Y., Zhang, Y., Dehaini, D., Chen, M., et al. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201707598 · Cited by 114 · see citing works
Krezalek, M. A., Hyoju, S. K., Zaborin, A., Okafor, E., Chandrasekar, L., Bindokas, V., Guyton, K. L., Montgomery, C. P., Daum, R. S., Zaborina, O. Y., et al. (2017) · Annals of Surgery · doi:10.1097/sla.0000000000002173 · Cited by 109 · see citing works
In or out: Phagosomal escape of <i>Staphylococcus aureus</i>
Moldovan, A., & Fraunholz, M. J. (2019) · Cellular Microbiology · doi:10.1111/cmi.12997 · Cited by 106 · see citing works
Pumerantz, A. S., Muppidi, K., Agnihotri, S. A., et al. (2010) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2010.10.011 · Cited by 95 · see citing works
Bodro, M., Gudiol, C., García‐Vidal, C., et al. (2013) · Supportive Care in Cancer · doi:10.1007/s00520-013-2012-3 · Cited by 88 · see citing works
Abed, N., Hassane, F. S., Zouhiri, F., Mougin, J., Nicolas, V., Desmaële, D., Gref, R., & Couvreur, P. (2015) · Scientific Reports · doi:10.1038/srep13500 · Cited by 88 · see citing works
Remote‐Loaded Platelet Vesicles for Disease‐Targeted Delivery of Therapeutics
Man, Y. M., Zhuang, J., Wei, X., Zhang, X., Zhang, Y., Jiang, Y., Dehaini, D., Chen, M., Gu, S., Gao, W., et al. (2018) · Advanced Functional Materials · doi:10.1002/adfm.201801032 · Cited by 87 · see citing works
Johnson, M. B., & Criss, A. K. (2013) · Journal of Visualized Experiments · doi:10.3791/50729 · Cited by 85 · see citing works
Super-resolution imaging in live cells
Cox, S. (2014) · Developmental Biology · doi:10.1016/j.ydbio.2014.11.025 · Cited by 80 · see citing works
Peritoneal GATA6+ macrophages function as a portal for Staphylococcus aureus dissemination
Jorch, S. K., Surewaard, B. G. J., Hossain, M., Peiseler, M., Deppermann, C., Deng, J., Bogoslowski, A., van der Wal, F., Omri, A., Hickey, M. J., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci127286 · Cited by 77 · see citing works
McGaha, T. L., & Karlsson, M. C. I. (2015) · Immunological Reviews · doi:10.1111/imr.12382 · Cited by 63 · see citing works
Apoptosis and Compensatory Proliferation Signaling Are Coupled by CrkI-Containing Microvesicles
Gupta, K. H., Goldufsky, J. W., Wood, S. J., Tardi, N. J., Moorthy, G. S., Gilbert, D. Z., Zayas, J. P., Hahm, E., Altintas, M. M., Reiser, J., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.05.014 · Cited by 61 · see citing works
Baltch, A. L., Ritz, W. J., Bopp, L. H., Michelsen, P. B., & Smith, R. P. (2007) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00973-06 · Cited by 46 · see citing works
Transportan 10 improves the pharmacokinetics and pharmacodynamics of vancomycin
Ruczyński, J., Rusiecka, I., Turecka, K., Kozłowska, A., Alenowicz, M., Gągało, I., Kawiak, A., Rekowski, P., Waleron, K., & Kocić, I. (2019) · Scientific Reports · doi:10.1038/s41598-019-40103-w · Cited by 45 · see citing works
Staphylococcus aureus induces DNA damage in host cell
Deplanche, M., Mouhali, N., Nguyen, M., Cauty, C., Ezan, F., Diot, A., Raulin, L., Dutertre, S., Langouët, S., Legembre, P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-44213-3 · Cited by 45 · see citing works
AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models
Chang, E., Pohling, C., Natarajan, A., Witney, T. H., Kaur, J., Xu, L., Gowrishankar, G., D’Souza, A. L., Murty, S., Schick, S., et al. (2015) · Journal of Neuro-Oncology · doi:10.1007/s11060-015-1972-1 · Cited by 42 · see citing works
Self-citationArntzen, M. Ø., & Thiede, B. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.010447 · Cited by 39 · see citing works
Sompel, D. V. D., Sasportas, L. S., Dragulescu‐Andrasi, A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045337 · Cited by 26 · see citing works
Campennì, A., Caruso, G., Barresi, V., et al. (2015) · The Kaohsiung Journal of Medical Sciences · doi:10.1016/j.kjms.2015.03.003 · Cited by 12 · see citing works
la Cruz-Hernández, I. D., Cornejo‐Juárez, P., Tellez-Miranda, O., Barrera-Pérez, L., Sandoval, S., Vilar‐Compte, D., Velázquez-Acosta, C., & Volkow-Fernández, P. A. (2019) · American Journal of Infection Control · doi:10.1016/j.ajic.2019.06.008 · Cited by 11 · see citing works
Molecular Imaging of Retinoic Acids in Live Cells Using Single-Chain Bioluminescence Probes
Kim, S. B., Fujii, R., Nishihara, R., Bose, R. J., Citterio, D., Suzuki, K. A. O., Massoud, T. F., & Paulmurugan, R. (2019) · ACS Combinatorial Science · doi:10.1021/acscombsci.9b00035 · Cited by 9 · see citing works
Self-citationBrain Abscess after Glioblastoma Resection: An Unusual Case Report
Raswan, U. S., Nayil, K., Makhdoomi, R. H., et al. (2017) · Surgical Infections Case Reports · doi:10.1089/crsi.2016.0015 · Cited by 2 · see citing works
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Research works printed but not linked: 1
- [35]Bai C; Li D; Zhang Q; Zheng S; Wang H; Li L; Zhang W. Prognostic Analysis of Cancer Patients with Staphylococcus aureus Infection: Five-Year Experience at a Comprehensive Cancer Center. Int. J. Clin. Exp. Med 2018, 11, 8640– 8645.
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Wu, Y., Cai, Z., Zhang, Y., Zheng, Y., Liao, L., & Jia, Z. (2026) · Bioactive Materials · doi:10.1016/j.bioactmat.2025.12.018 · Cited by 7 · see citing works
“Beyond biofilm formation, intracellular bacterial reservoirs within host cells pose a critical challenge in osteomyelitis by facilitating immune evasion and reducing antibiotic clearance, thereby contributing to the recurrence of refractory infections [40].”
- Authors
- Bose, R. J. C., Tharmalingam, N., Garcia Marques, F. J., Sukumar, U. K., Natarajan, A., Zeng, Y., Robinson, E., Bermudez, A., Chang, E., Habte, F., Pitteri, S. J., McCarthy, J. R., Gambhir, S. S., Massoud, T. F., Mylonakis, E., & Paulmurugan, R.
- Affiliations
- Stanford Medicine (US)
- Brown University (US)
- Stanford University , , 3155 Porter Drive , , ,
- Masonic Medical Research Laboratory (US)
- Corresponding author
- Paulmurugan, Ramasamy
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-04-29
- Volume
- 14
- Issue
- 5
- Pages
- 5818-5835
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC9116903
- OpenAlex
- W3020703473
- Cited by
- 84
- References
- 51
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 12 · 2023: 15 · 2022: 17 · 2021: 12 · 2020: 5
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Nano (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA209888, U54 CA199075)
- National Institute of Biomedical Imaging and Bioengineering (R21EB022298)
- Ben and Catherine Ivy Foundation
- Focused Ultrasound Foundation
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- Staphylococcus aureus, intracellular bacterial infection, macrophages, cancer cells, intracellular drug delivery, p53, targeted drug delivery, antibiotic resistance
- MeSH terms
- Extracellular Vesicles, Animals, Anti-Bacterial Agents, Macrophages, Microbial Sensitivity Tests, Neoplasms, Staphylococcal Infections, Staphylococcus aureus, Vancomycin, Mice
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