Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives

Mizukami, Shin; Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yoshiaki; Kikuchi, Kazuya

doi:10.1039/c6sc04435b

Cited by 18 publications

(18 citation statements)

References 36 publications

(27 reference statements)

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“… 25 Investigations using ALP as a target for killing cancer cells have shown positive results. 26 For example, ALP-mediated EISA is toxic to drug resistant uterine cancer cells. 6 d Here, ALP was chosen to dephosphorylate MelA2-P and further verify the feasibility of the ALP-mediated EIGF strategy.…”

Section: Resultsmentioning

confidence: 99%

Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues

Chen

et al. 2017

Chem. Sci.

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Section: Resultsmentioning

confidence: 99%

Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues

Chen

et al. 2017

Chem. Sci.

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“…The nanomedicine release rate is also a crucial factor identified in this study for enhanced free payload exposure in tumors. Tumor microenvironment-sensitive carriers have been developed to control nanomedicine release rates, including acid-triggered release, light-triggered release, and enzyme-triggered release [42–45]. These strategies can yield high free payload tumor concentrations and improved therapeutic efficacy [46].…”

Section: Discussionmentioning

confidence: 99%

Mathematical modeling of the heterogeneous distributions of nanomedicines in solid tumors

Liu

et al. 2019

European Journal of Pharmaceutics and Biopharmaceutics

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The distribution of nanomedicines inside solid tumors is often restricted to perivascular areas, leaving most distal tumor cells out of reach. This partly explains modest patient benefit of many nanomedicines compared to their free-form counterparts. The objective for this study is to develop a mathematical model to quantitatively analyze this phenomenon and the influencing factors to such perivascular distribution and seek for effective strategies to alleviate this. A spatial tumor distribution model was firstly constructed to mimic the geometrical structure of tumor vessels and the surrounding tumor cells. This tumor model was further integrated with a systemic pharmacokinetics model for nanoparticles. A variety of factors on the tumor spatial distributions of nanomedicines were considered in the model. With the model, we quantified the effect of these influencing factors on tumor delivery efficacy (ID %), the magnitude of heterogeneous distribution (H index), and the effect of enhanced permeability and retention (EPR). In particularly, we compared the spatial distributions of the nanoparticles and the free payloads insides tumors. The model predicted high degrees of distributional heterogeneity for both nanoparticles and free payloads. The degree of heterogeneity and the influencing factors for free payloads were markedly different from those for nanoparticles. We found that nanoparticle diffusion coefficient was the most effective factor in reducing the nanoparticle H index but exerted moderate influence on the free payloads H index. The most effective factor in reducing the H index of free payload was payload diffusion coefficient. The factors that improved free payload distribution were closely associated with higher drug efficacy. In contrast, the factors that improved nanoparticle spatial distributions did not always confer improved anti-tumor efficacy of the delivered drug. These findings highlight the importance of assessing the heterogeneous free payload distribution in tumors for the development of effective nanomedicines.

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“…Although we have focused so far in the delivery systems for AMPs, it has been reported that AMPs can also act as delivery vehicles [113,114] for bioactive compounds [115] or liposomes [116,117].…”

Section: Amps As Vehiclesmentioning

confidence: 99%

“…CIL showed good vehiculization capacity, silencing TNF-α expression for more than 14 h, a result that makes CIL complexes a promising tool for oligonucleotides delivery with application in gene silencing [115]. In addition, in previous years, a couple of works using AMPs as vehicles for targeted drug delivery systems were published [116,117]. Mizukami et al (2017) developed versatile stimuli responsive controlled release systems based on the combination of modified temporin L (TL) with surface-anionic liposomes.…”

Section: Amps As Vehiclesmentioning

confidence: 99%

“…Mizukami et al (2017) developed versatile stimuli responsive controlled release systems based on the combination of modified temporin L (TL) with surface-anionic liposomes. TL modifications consisted of: (i) The substitution of a Lys residue in TL for the protease-triggered system, or (ii) the substitution of a neutral amino acid for an anionic phosphorylated amino acid in the TL lipophilic region for the phosphatase-triggered system [116]. Zhang et al (2016) reported a vehiculization system for tumor delivery based on liposomes surface functionalization with the pH responsive AMP [D]-H6L9 [117].…”

Section: Amps As Vehiclesmentioning

confidence: 99%

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Nanosystems as Vehicles for the Delivery of Antimicrobial Peptides (AMPs)

et al. 2019

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Recently, antimicrobial peptides (AMPs), also called host defence peptides (HDPs), are attracting great interest, as they are a highly viable alternative in the search of new approaches to the resistance presented by bacteria against antibiotics in infectious diseases. However, due to their nature, they present a series of disadvantages such as low bioavailability, easy degradability by proteases, or low solubility, among others, which limits their use as antimicrobial agents. For all these reasons, the use of vehicles for the delivery of AMPs, such as polymers, nanoparticles, micelles, carbon nanotubes, dendrimers, and other types of systems, allows the use of AMPs as a real alternative to treatment with antibiotics.

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Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives

Abstract: Two strategies have been proposed to develop enzyme-triggered compound release systems.

Cited by 18 publications

References 36 publications

Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues

Selective inhibition of cancer cells by enzyme-induced gain of function of phosphorylated melittin analogues

Mathematical modeling of the heterogeneous distributions of nanomedicines in solid tumors

Nanosystems as Vehicles for the Delivery of Antimicrobial Peptides (AMPs)

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