Enhanced Efficacy and Broadening of Antibacterial Action of Drugs via the Use of Capped Mesoporous Nanoparticles

Mas, Nuria de; Galiana, Irene; Mondragón, Laura; Aznar, Elena; Climent, Estela; Cabedo, Nuria; Sancenón, Félix; Murguía, José Ramón; Martínez‐Máñez, Ramón; Marcos, M. Dolores; Amorós, Pedro

doi:10.1002/chem.201302170

Cited by 36 publications

(37 citation statements)

References 45 publications

(66 reference statements)

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“…The error bars present the SEM of at least two independent experiments in duplicate. bacteria, effort is also being directed toward the improving pharmacological properties, potency and delivery of known antibiotics, 19 , 45 , 27 , 46 , 20 Here we employed a recently described nanotechnology approach, 27 to enhance permeability of recently identified putative histidine kinase autophosphorylation inhibitors (HKAIs) in Gr− bacteria and demonstrated that they are bactericidal for Gr− bacteria. 12 The previously reported HKAIs were bactericidal for Gr + bacteria but not Gr− bacteria despite the fact they inhibit the autophosphorylation of HKs from both Gr− and Gr + in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…27 Figure 2 shows a schematic representation of the expected mechanism of action of N. Rho and N.HKAIs solids in the presence of Gr− bacteria. Standard procedures were used to characterize the prepared NP solids (see Supporting Information).…”

Section: Synthesis and Characterization Of Mesoporous Silica-based Namentioning

confidence: 99%

“…vancomycin 27 we performed confocal microscopy experiments. Incubation of E. coli DH5α with ePLL-capped NPs loaded with rhodamine resulted in concentration-dependent internalization of rhodamine (Figure 8).…”

Section: Epll-capped Nps Enhance the Internalization Of The Cargomentioning

confidence: 99%

“…27 MSNs loaded with vancomycin, functionalized with n-[(3-trimethoxysilyl)propyl]ethylendiamine (f) and capped with a cationic polymer of ε-poly-L-lysine (ePLL) showed an extended spectrum of activity against Gr− bacteria including E. coli (DH5α, 100, 405), Salmonella typhimurium and Erwinia carotovora. 27 Most Gr− pathogens are intrinsically resistant to vancomycin due to its relatively high molecular weight and size and inability to pass through porins in the OM, 28 but ePLL promoted ionic bonding of the nanoparticles loaded with vancomycin (N. Van) with the negatively charged OM and facilitated membrane permeability of vancomycin. 29 Moreover when ePLL and vancomycin were used in the N. Van nano-formulation a potent synergistic effect was observed which did not occur when ePLL and vancomycin were used alone.…”

mentioning

confidence: 99%

“…29 Moreover when ePLL and vancomycin were used in the N. Van nano-formulation a potent synergistic effect was observed which did not occur when ePLL and vancomycin were used alone. 27 To test whether the approach described above could extend the spectrum of activity of the HKAIs to Gr− bacteria we loaded MSNs with different inhibitors, rhodamine as a control, and then capped the functionalised nanoparticles (NPs) with ePLL. The minimal inhibitory concentrations (MICs) of the NPs alone, NPs loaded with rhodamine and capped with ePLL (N. Rho), ePLL alone, and different HKAIs loaded to nanoparticles capped with ePLL were determined using a standard double dilution method and compared to the free HKAIs.…”

mentioning

confidence: 99%

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Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Velikova

Mas

Miguel-Romero

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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Two-component systems (TCS) regulate diverse processes such as virulence, stress responses, metabolism and antibiotic resistance in bacteria but are absent in humans, making them promising targets for novel antibacterials. By incorporating recently described TCS histidine kinase autophosphorylation inhibitors (HKAIs) into ε-poly-L-lysine capped nanoparticles (NPs) we could overcome the Gram negative (Gr−) permeability barrier for the HKAIs. The observed bactericidal activity against Gr− bacteria was shown to be due to the enhanced delivery and internalization of the HKAIs and not an inhibitory or synergistic effect of the NPs. The NPs had no adverse effects on mammalian cell viability or the immune function of macrophages in vitro and showed no signs of toxicity to zebrafish larvae in vivo. These results show that HKAIs are promising antibacterials for both Gr− and Gr + pathogens and that NPs are a safe drug delivery technology that can enhance the selectivity and efficacy of HKAIs against bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Synthesis and Characterization Of Mesoporous Silica-based Namentioning

confidence: 99%

Section: Epll-capped Nps Enhance the Internalization Of The Cargomentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Velikova

Mas

Miguel-Romero

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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The High Potential of ε‐Poly‐l‐Lysine for the Development of Antimicrobial Biomaterials

Lebaudy,

Guilbaud-Chéreau,

Frisch

et al. 2023

Advanced NanoBiomed Research

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ε‐poly‐l‐lysine (ε‐PLL) is a natural polypeptide/polycation originating from bacteria. Thanks to its antifungal and antibacterial properties, it is the subject of extensive research in the food and medical industries. ε‐PLL is also used to develop biomaterials in a broad range of applications, such as drug delivery, wound healing, or antimicrobial coatings. Indeed, loading ε‐PLL inside nanoparticles, functionalizing implant surfaces with ε‐PLL, or developing hydrogels based on reactions between ε‐PLL and other polymers can improve the materials properties, leading to biocompatible, antibacterial, and antifungal systems. These characteristics are necessary not only for the development of biomaterials, for their integrity in a biological environment, but also for improving the performances of medical devices. Moreover, ε‐PLL can be used as an alternative to antibiotics as its mechanism of action reduces the bacterial resistance risk compared with antibiotics. Finally, “smart” systems using ε‐PLL may be developed, with controllable material degradation or drug delivery via pH or temperature variations. This review sought to gather the latest research on the development of antimicrobial biomaterials based on the ε‐PLL polypeptide.

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Chromo‐Fluorogenic Detection of Nitroaromatic Explosives by Using Silica Mesoporous Supports Gated with Tetrathiafulvalene Derivatives

Salinas

Solano

Sørensen

et al. 2013

Chemistry A European J

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Three new hybrid gated mesoporous materials (SN3 -1, SNH2 -2, and SN3 -3) loaded with the dye [Ru(bipy)3 ](2+) (bipy=bipyridine) and capped with different tetrathiafulvalene (TTF) derivatives (having different sizes and shapes and incorporating different numbers of sulfur atoms) have been prepared. The materials SN3 -1 and SN3 -3 are functionalized on their external surfaces with the TTF derivatives 1 and 3, respectively, which were attached by employing the "click" chemistry reaction, whereas SNH2 -2 incorporates the TTF derivative 2, which was anchored to the solid through an amidation reaction. The final gated materials have been characterized by standard techniques. Suspensions of these solids in acetonitrile showed "zero release", most likely because of the formation of dense TTF networks around the pore outlets. The release of the entrapped [Ru(bipy)3 ](2+) dye from SN3 -1, SNH2 -2, and SN3 -3 was studied in the presence of selected explosives (Tetryl, TNT, TNB, DNT, RDX, PETN, PA, and TATP). SNH2 -2 showed a fairly selective response to Tetryl, whereas for SN3 -1 and SN3 -3 dye release was found to occur with Tetryl, TNT, and TNB. The uncapping process in the three materials can be ascribed to the formation of charge-transfer complexes between the electron-donating TTF units and the electron-accepting nitroaromatic explosives. Finally, solids SNH2 -2 and SN3 -1 have been tested for Tetryl detection in soil with good results, pointing toward a possible use of these or similar hybrid capped materials as probes for the selective chromo-fluorogenic detection of nitroaromatic explosives.

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Enhanced Efficacy and Broadening of Antibacterial Action of Drugs via the Use of Capped Mesoporous Nanoparticles

Cited by 36 publications

References 45 publications

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

Broadening the antibacterial spectrum of histidine kinase autophosphorylation inhibitors via the use of ε-poly-L-lysine capped mesoporous silica-based nanoparticles

The High Potential of ε‐Poly‐l‐Lysine for the Development of Antimicrobial Biomaterials

Chromo‐Fluorogenic Detection of Nitroaromatic Explosives by Using Silica Mesoporous Supports Gated with Tetrathiafulvalene Derivatives

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