Drug delivery nanoplatforms have been applied in bioimaging, medical diagnosis, drug delivery and medical therapy. However, insolubility, toxicity, instability, nonspecific targeting and short retention of many hydrophobic drugs limit their extensive applications. Herein, we have constructed a passive targeting and long retention therapeutic nanoplatform of core–shell gefitinib/poly (ethylene glycol)-polytyrosine nanocomplexes (Gef-PY NCs). The Gef-PY NCs have good water-solubility, non-toxicity (correspond to 1/10 dosage of effective gefitinib (hydrochloride) (Gef·HCl) (normal drug administration and slow-release) and high stability (120 days, 80% drug retention at 4 or 25 °C). The core–shell Gef-PY NCs present unexpected kidney targeting and drug slow-release capacity (ca. 72 h). The good water-solubility, non-toxicity and high stability of Gef-PY NCs effectively solve the bottleneck question that Gef-based therapy could be used only in intraperitoneal injection due to its insolubility and severe toxicity. Such excellent properties (e.g., water-solubility, non-toxicity, high stability, kidney targeting and long retention) of Gef-PY NCs create their prominent anti-fibrosis capabilities, such as decreasing approximately 40% tubulointerstitial fibrosis area and 68% expression of collagen I within 7 days. This therapeutic efficacy is well-matched with that of 10 times the dosage of toxic Gef·HCl. It is very hopeful that Gef-PY NCs could realize clinical applications and such a strategy offers an effective route to design high-efficiency treatments for kidney- and tumor-related diseases.

中文翻译：

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构建基于水溶性、无毒和高度稳定的核壳聚（氨基酸）纳米复合物的被动靶向和长保留治疗纳米平台

药物递送纳米平台已应用于生物成像、医学诊断、药物递送和医学治疗。然而，许多疏水性药物的不溶性、毒性、不稳定性、非特异性靶向和短保留限制了它们的广泛应用。在此，我们构建了核壳吉非替尼/聚（乙二醇）-聚酪氨酸纳米复合物（Gef-PY NCs）的被动靶向和长保留治疗纳米平台。Gef-PY NCs具有良好的水溶性、无毒性（相当于有效吉非替尼（盐酸盐）（Gef·HCl）的1/10剂量（正常给药和缓释）和高稳定性（120天，80%）药物保留在 4 或 25 °C。核壳 Gef-PY NCs 表现出意想不到的肾脏靶向和药物缓释能力（大约72 小时）。Gef-PY NCs良好的水溶性、无毒和高稳定性，有效地解决了Gef基治疗因不溶性和毒性严重而只能用于腹腔注射的瓶颈问题。如此优异的性能（例如Gef-PY NCs 的水溶性、无毒、高稳定性、肾脏靶向和长保留）创造了它们突出的抗纤维化能力，例如在 7 天内减少约 40% 的肾小管间质纤维化面积和 68% 的胶原蛋白 I 表达. 这种疗效与毒性Gef·HCl 10倍剂量的疗效相当。Gef-PY NCs有望实现临床应用，这样的策略为设计肾脏和肿瘤相关疾病的高效治疗提供了有效途径。