Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey 07110, United States.
Department of Chemistry and Chemical Biology, Stevens Institute of Technology, Hoboken, New Jersey 07030, United States.
ACS Appl Mater Interfaces. 2023 Feb 8;15(5):6312-6325. doi: 10.1021/acsami.2c17214. Epub 2023 Jan 26.
Precision nanomedicine can be employed as an alternative to chemo- or radiotherapy to overcome challenges associated with the often narrow therapeutic window of traditional treatment approaches, while safely inducing effective, targeted antitumor responses. Herein, we report the formulation of a therapeutic nanocomposite comprising a hyaluronic acid (HA)-coated gold nanoframework (AuNF) delivery system and encapsulated IT848, a small molecule with potent antilymphoma and -myeloma properties that targets the transcriptional activity of nuclear factor kappa B (NF-κB). The porous AuNFs fabricated via a liposome-templated approach were loaded with IT848 and surface-functionalized with HA to formulate the nanotherapeutics that were able to efficiently deliver the payload with high specificity to myeloma and lymphoma cell lines studies characterized biodistribution, pharmacokinetics, and safety of HA-AuNFs, and we demonstrated superior efficacy of HA-AuNF-formulated IT848 free IT848 in lymphoma mouse models. Both and results affirm that the AuNF system can be adopted for targeted cancer therapy, improving the drug safety profile, and enhancing its efficacy with minimal dosing. HA-AuNF-formulated IT848 therefore has strong potential for clinical translation.
精准纳米医学可以作为化学疗法或放射疗法的替代方法，克服传统治疗方法治疗窗口往往较窄的相关挑战，同时安全地诱导有效、靶向的抗肿瘤反应。在此，我们报告了一种治疗性纳米复合材料的制剂，该复合材料由透明质酸（HA）包覆的金纳米框架（AuNF）递药系统和封装的 IT848 组成，IT848 是一种具有强效抗淋巴瘤和骨髓瘤特性的小分子，靶向核因子 kappa B（NF-κB）的转录活性。通过脂质体模板法制备的多孔 AuNF 被负载 IT848，并通过 HA 表面功能化来制备纳米药物，该纳米药物能够高效、高特异性地将有效载荷递送至骨髓瘤和淋巴瘤细胞系。我们研究了 HA-AuNF 的生物分布、药代动力学和安全性，并证明了 HA-AuNF 制剂的 IT848 在淋巴瘤小鼠模型中具有优越的疗效，优于游离的 IT848。体内和体外研究均证实，AuNF 系统可用于靶向癌症治疗，提高药物安全性，并通过最小剂量增强其疗效。因此，HA-AuNF 制剂的 IT848 具有很强的临床转化潜力。
