Antibiotic-Derived Lipid Nanoparticles to Treat Intracellular <i>Staphylococcus aureus</i>

Zhang, Chengxiang; Zhao, Weiliang; Bian, Cong; Hou, Xucheng; Deng, Binbin; McComb, David W.; Chen, Xiaofang; Dong, Yizhou

doi:10.1021/acsabm.8b00821

Cited by 24 publications

(18 citation statements)

References 33 publications

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“…Bioactive Molecules Derived Lipids. Lipids incorporating various bioactive molecules, such as oligopeptides/ amino acids, sugar, 575 and small molecular drugs, 59,576,577 have been developed as formulation components for RNA delivery. Cholesterol, for example, is biologically compatible and generally used as a helper lipid to stabilize the LNPs.…”

Section: Ionizable Lipidsmentioning

confidence: 99%

Lipids and Lipid Derivatives for RNA Delivery

et al. 2021

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RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability. LNPs represent the most widely used delivery systems for RNA-based therapeutics, as evidenced by the clinical approvals of three LNP-RNA formulations, patisiran, BNT162b2, and mRNA-1273. This review covers recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades. We focus mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure–activity relationships. We also briefly describe the current status of representative preclinical studies and clinical trials and highlight future opportunities and challenges.

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Section: Ionizable Lipidsmentioning

confidence: 99%

Lipids and Lipid Derivatives for RNA Delivery

et al. 2021

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“…Many approaches have been investigated to achieve this. For example, fabrication of a nanoparticle delivery vector system employing liposomes, nanohydrogels, or polymer-based nanoparticles have been designed to overcome cellular barriers allowing for enhanced uptake of antibiotics. − Although these approaches provide effective therapeutic efficacy toward intracellular pathogen, nanoparticles are also associated with a complicated synthesis process requiring considerable effort to achieve entrapment optimization for each new cargo. Additionally, engineered peptides containing methotrexate (MTX), or anti-S.…”

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confidence: 99%

Overcoming Planktonic and Intracellular Staphylococcus aureus-Associated Infection with a Cell-Penetrating Peptide-Conjugated Antimicrobial Peptide

et al. 2020

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Staphylococcus aureus is a primary pathogen responsible for causing postoperative infections as it survives and persists in host cells, including osteoblasts and macrophages. These cells then serve as reservoirs resulting in chronic infections. Most traditional antibiotics have poor effects on intracellular S. aureus because they cannot enter the cell. Herein, a cell-penetrating peptide TAT-KR-12 was derived from the trans-activating transcription (TAT) peptide and KR-12 (residues 18–29 of human cathelicidin LL-37). The TAT acts as a “trojan horse” to deliver KR-12 peptide into the cells to kill S. aureus. Moreover, effective antibacterial properties and biocompatibility were observed in vitro, demonstrating that TAT-KR-12 is effective not only in eliminating planktonic S. aureus, but also in eliminating intracellular S. aureus cells in vitro. TAT-KR-12, as with LL-37, also elicits strong anti-inflammatory activities in LPS-stimulated macrophages, as demonstrated by significant inhibition of NO, TNF-α, and IL-1β expression and secretion from LPS-stimulated RAW264.7 cells. In the subcutaneous infection mouse model of planktonic and intracellular infections, the growth of S. aureus in vivo is evidently inhibited without cytotoxicity. These results suggest that the novel antimicrobial TAT-KR-12 may prove to be an effective treatment option to overcome antibiotic resistance caused by intracellular bacterial infections.

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“…4a). Nanomedicine has been widely used due to its success in eradicating drug-resistant bacteria in vitro or in vivo [27][28][29][30][31][32]. We focused on the effect of nanocarriers encapsulating two drugs on the treatment of the bacteremia induced by MRSA.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice

Liao

Yang

et al. 2021

J Nanobiotechnol

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Background Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. Results The mean nanoparticle size and zeta potential of the NLCs were 171 nm and − 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. Conclusions The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

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Antibiotic-Derived Lipid Nanoparticles to Treat Intracellular Staphylococcus aureus

Cited by 24 publications

References 33 publications

Lipids and Lipid Derivatives for RNA Delivery

Lipids and Lipid Derivatives for RNA Delivery

Overcoming Planktonic and Intracellular Staphylococcus aureus-Associated Infection with a Cell-Penetrating Peptide-Conjugated Antimicrobial Peptide

Multifunctional lipid-based nanocarriers with antibacterial and anti‐inflammatory activities for treating MRSA bacteremia in mice

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