Nanomaterials and molecular transporters to overcome the bacterial envelope barrier: Towards advanced delivery of antibiotics

Santos, Rita S.; Figueiredo, Céu; Azevedo, Nuno F.; Braeckmans, Kevin; Smedt, Stefaan C. De

doi:10.1016/j.addr.2017.12.010

Cited by 98 publications

(100 citation statements)

References 230 publications

(553 reference statements)

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“…The latter trend has been increasingly described as a promising way to discover novel anti‐infective agents. In fact, the conjugation of ATBs with siderophores, peptides (eg, AMPs and cell‐penetrating peptides [CPPs]), antibodies, and nanoparticles (NPs) are effective representative examples of the Trojan horse strategy. These approaches have resulted in many candidates demonstrating potent antibacterial activity and some of these candidates are currently at the clinical investigation stage .…”

Section: Introductionmentioning

confidence: 99%

“…165 (59) was covalently attached to (60) through a glutaric anhydride linker to create the conjugate CAP-UBI 29-41 (61, Figure 12). The ester bond between CAP and glutaric-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] part can be easily broken by enzymatic hydrolysis. 165,166 CAP and its conjugate (61) were then evaluated for their antibacterial activity as well as their cytotoxicity on normal cells (Table 8).…”

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confidence: 99%

“…165 Both CAP and conjugate (61) exhibited greater effects in Gram-negative (ie, E. coli) than in Gram-positive bacteria (ie, S. aureus). The attachment of UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] (60) to CAP (59) is likely favorable to antibiotic permeability and ATB activity. In terms of biocytotoxicity, CAP caused a remarkable decrease in the population of leukocytes and neutrophils when compared to the control (ie, saline) (4.46 and 0.24 × 10 9 /L vs 8.17 and 1.46 × 10 9 /L, respectively).…”

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confidence: 99%

“…In contrast, conjugate (61) was less toxic towards leukocytes and neutrophils (7.30 and 0.98 × 10 9 /L, respectively) ( Table 8). 165 In addition, the release ratios of CAP (59) from CAP-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] (61), mediated by hydrolases, were less than 50% within 8 hours, allowing the majority of conjugates to reach the bacteria-infected tissues. 165 Therefore, CAP-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] (61) has potential as a prodrug, in which…”

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confidence: 99%

“…F I G U R E 1 2 Structure of CAP and of its conjugate CAP-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] . 165…”

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confidence: 99%

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Drug delivery systems designed to overcome antimicrobial resistance

Pham

Loupias

Dassonville‐Klimpt

et al. 2019

Medicinal Research Reviews

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Antimicrobial resistance has emerged as a huge challenge to the effective treatment of infectious diseases. Aside from a modest number of novel anti‐infective agents, very few new classes of antibiotics have been successfully developed for therapeutic use. Despite the research efforts of numerous scientists, the fight against antimicrobial (ATB) resistance has been a longstanding continued effort, as pathogens rapidly adapt and evolve through various strategies, to escape the action of ATBs. Among other mechanisms of resistance to antibiotics, the sophisticated envelopes surrounding microbes especially form a major barrier for almost all anti‐infective agents. In addition, the mammalian cell membrane presents another obstacle to the ATBs that target intracellular pathogens. To negotiate these biological membranes, scientists have developed drug delivery systems to help drugs traverse the cell wall; these are called “Trojan horse” strategies. Within these delivery systems, ATB molecules can be conjugated with one of many different types of carriers. These carriers could include any of the following: siderophores, antimicrobial peptides, cell‐penetrating peptides, antibodies, or even nanoparticles. In recent years, the Trojan horse‐inspired delivery systems have been increasingly reported as efficient strategies to expand the arsenal of therapeutic solutions and/or reinforce the effectiveness of conventional ATBs against drug‐resistant microbes, while also minimizing the side effects of these drugs. In this paper, we aim to review and report on the recent progress made in these newly prevalent ATB delivery strategies, within the current context of increasing ATB resistance.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

“…F I G U R E 1 2 Structure of CAP and of its conjugate CAP-UBI [29][30][31][32][33][34][35][36][37][38][39][40][41] . 165…”

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confidence: 99%

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Drug delivery systems designed to overcome antimicrobial resistance

Pham

Loupias

Dassonville‐Klimpt

et al. 2019

Medicinal Research Reviews

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Functional Materials to Overcome Bacterial Barriers and Models to Advance Their Development

Bali

Kamal

Mulla

et al. 2023

Adv Funct Materials

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With the emerging problem of antimicrobial resistance, the world is facing a slow but dangerous pandemic. While the discovery of novel antibiotics is reaching a nearly exhaustive end, new concepts for anti‐infective drugs are emerging. So‐called pathoblockers aim to de‐weaponize bacteria rather than just killing them. As the target of these molecules is typically located intracellularly, however, hitherto almost unnoticed biological barriers are emerging such as the biofilm matrix, the bacterial cell envelope, efflux pumps, and eventual bacterial metabolism. This leads to a new paradigm that is to maximize bacterial bioavailability. To overcome the bacterial barriers, especially when further optimization of the active molecules is not possible, functional materials are needed to engineer innovative delivery systems. Those may not only enable novel anti‐infective molecules to reach their targets, but will also improve the bacterial bioavailability of existing anti‐infectives. Additionally, there is a need for better infection models that allow studying drug effects on both the bacteria and the host in a relevant manner as needed for rational anti‐infective drug development.

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Intrabacterial Nitroreductase‐Activated Imaging and Persistently Illuminated Photodynamic Therapy for Intracellular Infection Theranostics

Ran,

Cao,

Zheng

et al. 2024

Adv Funct Materials

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Intracellular bacterial (ICB) infection is one of the most life‐threatening cases of drug resistance, and photodynamic therapy (PDT) is challenged by limited light penetration into tissues and unspecific toxicity to host cells. Herein, theranostic nanoparticles (NPs) are developed to facilitate on‐demand activation of photosensitizers inside ICBs and persistent PDT of deep‐tissue ICB infections. Mechanoluminescent SrAl2O4:Eu2+ and persistence luminescent CaS:Eu2+ are sequentially deposited on mesoporous silica to prepare mSC, followed by encapsulation by bacterial membranes with loaded nitroreductase (NTR)‐activatable methylene blue (nMB) to obtain mSC‐nMB@BM NPs. The fluorescence quenching of nMB with mSC offers few cytotoxicities even under ultrasonication, and bacterial membrane coatings mediate the specific NP internalization into ICB‐infected macrophages. Bacterial pore‐forming toxins trigger nMB release from NPs, and intrabacterial NTR rejuvenates methylene blue probes from nMB for real‐time imaging of ICB infections. Ultrasonication of NPs continuously excites the rejuvenated methylene blue to generate reactive oxidative species and reduce viable ICBs by 3.54 log magnitude folds. NP treatment on ICB‐infected mice exhibits full survival and restores viscera functions without any pathological abnormality. Therefore, this concise NP design demonstrates capabilities of bacterial membrane‐mediated specific internalization, bacterial toxin‐triggered release and intrabacterial NTR‐rejuvenation of fluorescent probes, and persistent internal light‐illumination for ICB theranostics.

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Nanomaterials and molecular transporters to overcome the bacterial envelope barrier: Towards advanced delivery of antibiotics

Cited by 98 publications

References 230 publications

Drug delivery systems designed to overcome antimicrobial resistance

Drug delivery systems designed to overcome antimicrobial resistance

Functional Materials to Overcome Bacterial Barriers and Models to Advance Their Development

Intrabacterial Nitroreductase‐Activated Imaging and Persistently Illuminated Photodynamic Therapy for Intracellular Infection Theranostics

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