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首页> 外文期刊>Biomaterials Science >Photo synthesis of protein-based drug-delivery nanoparticles for active tumor targeting
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Photo synthesis of protein-based drug-delivery nanoparticles for active tumor targeting

机译：用于主动靶向肿瘤的基于蛋白质的药物递送纳米粒子的光合成

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Recently, nanometer-sized drug-delivery systems (DDSs) with an active targeting function to tumor sites have been cinfirmed to have great efficiency for cancer chemotherapy. However, the use of complicated modification techniques and the poor graft efficiency of the targeting ligands on the surface of the DDS have largely limited the application of most of the nano-DDSs. Especially for protein-based nano-DDSs, grafting of targeting ligands often requires genetic modification of the protein sequences, which is laborious and inefficient. Here, we present a novel method to photo synthesize a protein-based drug-delivery system with an active targeting function to tumor sites. The disulfide bonds in protein bovine α-lactalbumin (BLA) can be ruptured by controlled UV illumination, which triggers the formation of nano-sized protein aggregates and releases free thiol groups for the modification of the active targeting ligand of circular RGD peptide. Moreover, we demonstrated that the anti-cancer drug doxorubicin (DOX) can be loaded onto the protein-based DDS during the photo synthesis step. The synthesis approach is very convenient and cost-effective and can be accomplished under physiological conditions. Both in vitro and in vivo experiments validate that this DDS system possesses a much greater drug-delivery efficiency to the tumor sites and a better inhibition capability of tumor growth than the unmodified counterparts. This novel drug-delivery system can find broad applications in cancer chemotherapy. Moreover, our synthetic strategy can be easily extended to other disulfide-containing proteins and greatly expand the toolbox of protein-based DDSs for active targeting.
机译：近来，已经证实具有对肿瘤部位的主动靶向功能的纳米级药物递送系统（DDS）对于癌症化学疗法具有很大的效率。然而，使用复杂的修饰技术以及DDS表面上靶向配体的较差的接枝效率大大限制了大多数纳米DDS的应用。特别是对于基于蛋白质的纳米DDS，靶向配体的接枝通常需要对蛋白质序列进行遗传修饰，这既费力又效率低下。在这里，我们提出了一种新颖的方法来光合成具有主动靶向功能的基于蛋白质的蛋白质递送系统对肿瘤部位。蛋白质牛α-乳白蛋白（BLA）中的二硫键可通过受控的紫外线照射破坏，从而触发纳米级蛋白质聚集体的形成并释放出游离的巯基，以修饰环状RGD肽的活性靶向配体。此外，我们证明了抗癌药物阿霉素（DOX）可以在光合成步骤中加载到基于蛋白质的DDS上。该合成方法非常方便且具有成本效益，并且可以在生理条件下完成。体外和体内实验均证实，该DDS系统与未修饰的对应物相比，具有更大的向肿瘤部位的药物递送效率和更好的肿瘤生长抑制能力。这种新颖的药物递送系统可以在癌症化疗中找到广泛的应用。此外，我们的合成策略可以轻松扩展到其他含二硫键的蛋白质，并大大扩展了基于蛋白质的DDS主动靶向的工具箱。

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