Reconstructed Apoptotic Bodies as Targeted "Nano Decoys" to Treat Intracellular Bacterial Infections within Macrophages and Cancer Cells

被引：66

作者：

Bose, Rajendran J. C. ^{[3
]}

Tharmalingam, Nagendran ^{[4
,5
]}

Marques, Fernando J. Garcia ^{[2
]}

Sukumar, Uday Kumar ^{[3
]}

Natarajan, Arutselvan ^{[3
]}

Zeng, Yitian ^{[3
]}

Robinson, Elise ^{[3
]}

Bermudez, Abel ^{[2
]}

Chang, Edwin ^{[3
]}

Habte, Frezghi ^{[3
]}

Pitteri, Sharon J. ^{[2
]}

McCarthy, Jason R. ^{[6
]}

Gambhir, Sanjiv S. ^{[1
,2
]}

Massoud, Tarik F. ^{[3
]}

Mylonakis, Eleftherios ^{[4
,5
]}

Paulmurugan, Ramasamy ^{[1
,2
]}

机构：

[1] Stanford Univ, Mol Imaging Program Stanford MIPS, Sch Med, Dept Radiol,Canary Ctr & Stanford Canc Early Dete, Palo Alto, CA 94305 USA

[2] Stanford Univ, Dept Radiol, Canary Ctr Stanford Canc Early Detect, Sch Med, Palo Alto, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford MIPS, Palo Alto, CA 94305 USA

[4] Brown Univ, Infect Dis Div, Dept Med, Rhode Isl Hosp, Providence, RI 02903 USA

[5] Brown Univ, Alpert Med Sch, Providence, RI 02903 USA

[6] Masonic Med Res Instil Ute, Utica, NY 13501 USA

来源：

ACS NANO | 2020年 / 14卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Staphylococcus aureus; apoptotic bodies; vancomycin; bacterial therapy; antibiotics; macrophages; cancer cells; CARE-ASSOCIATED INFECTIONS; IDENTIFICATION; EPIDEMIOLOGY; GLIOMAS;

D O I：

10.1021/acsnano.0c00921

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：5818 / 5835

页数：18

共 52 条

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