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首页> 外文期刊>RSC Advances >Simple and tunable surface coatings via polydopamine for modulating pharmacokinetics, cell uptake and biodistribution of polymeric nanoparticles
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Simple and tunable surface coatings via polydopamine for modulating pharmacokinetics, cell uptake and biodistribution of polymeric nanoparticles

机译：通过聚多巴胺 制备的简单可调节的表面涂层，用于调节高分子纳米颗粒的药代动力学，细胞吸收和生物分布

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Nanosystems often require different surface coatings to improve their biocompatibility, circulating time, the intracellular uptake and reduce toxic side effects. A pre-understanding and a simple controlling of the surface coatings' interactions with biological systems are of vital importance. Herein, we successfully modified model nanoparticles (NPs) with three surface modifiers: bovine serum albumin (BSA), poly-L-lysine (PLL) and polyethylene glycol (PEG) simply and uniformly via polydopamine (pD). Following, the serum stability, drug release profile, pharmacokinetics, in vivo biodistribution and interactions with tumor cells of these modified nanoparticles were systematically evaluated for further applications. According to the in vitro and in vivo results, BSA coated NPs could inhibit the plasma proteins' adsorption thus prolong their circulation time to some extent. In addition, the BSA shell showed good biocompatibility, non-toxicity and a delayed drug release. Interestingly, PLL coated NPs exhibited higher and pH-dependent intracellular uptake and antitumor activity in an acidic tumor micro environment. Nonetheless, the PLL coating did not exhibit particularly high toxicity due to its low positive charge density. PEG coated NPs displayed good pharmacokinetic profiles as expected. In the light of the successful application of the above pD–surface modifier compound shells (pD–BSA, pD–PLL, pD–PEG), diverse particles can be modified to selectively optimize their nature and achieve the goal such as improved pharmacokinetic profiles, enhanced cellular internalization ability and lower toxicity. This strategy that can selectively alter the biological fate of NPs simply by tunable coatings provides great potential for controllable drug delivery systems for cancer and other therapeutic or diagnostic applications.
机译：纳米系统通常需要不同的表面涂层，以改善其生物相容性，循环时间，细胞内摄取并减少毒性副作用。对表面涂层与生物系统的相互作用进行预先了解和简单控制至关重要。在这里，我们成功地通过三种表面修饰剂成功地修饰了模型纳米颗粒（NPs）：牛血清白蛋白（BSA），聚 L -赖氨酸（PLL）和聚乙二醇（PEG），并且通过 聚多巴胺（pD）。随后，系统地评估了这些修饰的纳米粒子的血清稳定性，药物释放曲线，药代动力学，体内生物分布以及与肿瘤细胞的相互作用，以供进一步应用。根据体外和体内的结果，BSA包被的NPs可以抑制血浆蛋白的吸附，从而在一定程度上延长其循环时间。此外，BSA外壳显示出良好的生物相容性，无毒和延迟的药物释放。有趣的是，在酸性肿瘤微环境中，PLL包被的NPs表现出更高且依赖pH的细胞内摄取和抗肿瘤活性。但是，PLL涂层由于其低的正电荷密度而没有表现出特别高的毒性。 PEG包被的NPs表现出良好的药代动力学特征。鉴于上述pD-表面修饰剂化合物壳（pD-BSA，pD-PLL，pD-PEG）的成功应用，可以修饰各种颗粒，以选择性地优化其性质并实现诸如改善药代动力学特性的目标，增强细胞内在化能力并降低毒性。只需通过可调涂层即可选择性地改变NP的生物学命运的这一策略为癌症和其他治疗或诊断应用的可控药物递送系统提供了巨大潜力。

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