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首页> 外文期刊>Acta biomaterialia >Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from 'soft' nanoparticles
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Engineered peptides with enzymatically cleavable domains for controlling the release of model protein drug from 'soft' nanoparticles

机译：具有酶切结构域的工程化多肽，用于控制模型蛋白质药物从“软”纳米颗粒的释放

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Matrix metalloproteinase-2 (MMP-2) is an endopeptidase that has been shown to be present in high concentrations during most tissue remodeling events, including disease states like active tumor sites, thus making it an attractive molecule for use in effecting local delivery of therapeutic molecules. Moreover, the use of non-toxic and biodegradable nanoparticles for controlled drug delivery is highly sought after. To this end, bovine serum albumin (BSA) nanoparticles (NPs) were stabilized with coatings formed using domains of varying sensitivity to MMP-2, viz. K 6GPQG/IASQK 6 and K 6HPVG/LLARK 6, lysine residues being used to facilitate peptide immobilization to the BSA NPs via electrostatic interactions, and peptide domains that have a high (HPVG/LLAR) and low (GPQG/IASQ) MMP-2 cleavage rate. The MMP-2-induced cleavage rates of these two domains (the position of action being noted with a "/") have differing kinetics that can be used to provide a novel mechanism for facilitating the controlled release of molecules where local concentrations of MMP-2 are high. It was found that both surface concentration and cleavage domain type influenced the release of the model drug (BSA) from these NPs. This stratagem may provide a novel pathway for developing multi-functional coatings for controlling the local delivery of therapeutics at sites where the presence of various enzymes exist as a function of tissue state.
机译：基质金属蛋白酶2（MMP-2）是一种内肽酶，已被证明在大多数组织重塑过程中都以高浓度存在，包括疾病状态（如活跃的肿瘤部位），因此使其成为一种有吸引力的分子，可用于局部治疗药物分子。此外，非常需要使用无毒且可生物降解的纳米颗粒来控制药物的递送。为此，牛血清白蛋白（BSA）纳米颗粒（NPs）用对MMP-2具有不同敏感性的结构域形成的涂层稳定。 K 6GPQG / IASQK 6和K 6HPVG / LLARK 6赖氨酸残基用于通过静电相互作用促进肽固定在BSA NP上，以及具有高（HPVG / LLAR）和低（GPQG / IASQ）MMP-2的肽域卵裂率。 MMP-2诱导的这两个域的切割速率（作用位置用“ /”标记）具有不同的动力学，可用于提供新颖的机制来促进分子的受控释放，其中局部浓度的MMP- 2个很高。发现表面浓度和切割结构域类型都影响从这些NP释放模型药物（BSA）。该策略可以为开发多功能涂层提供新途径，该多功能涂层用于控制根据组织状态而存在各种酶的部位的治疗剂的局部递送。

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