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基于阿仑膦酸的发光胶束纳米结构用于潜在的骨靶向递送胆钙化醇

Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol.

机构信息

CNR-Institute for Chemical and Physical Process, 70125 Bari, Italy.

Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), 50121 Firenze, Italy.

出版信息

Molecules. 2024 May 17;29(10):2367. doi: 10.3390/molecules29102367.

Abstract

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

摘要

维生素 D 是一种必需的微量营养素,对骨骼完整性和各种非骨骼生理功能至关重要,但在体内的生物利用度和稳定性有限。本研究专注于开发聚乙二醇(PEG)接枝磷脂胶束纳米结构,共同包封维生素 D3 并与阿仑膦酸偶联,旨在实现主动骨靶向。此外,通过同时包封维生素 D3 和碳点,这些纳米结构在电磁光谱的紫外可见区域具有光学可追踪性,碳点是一类新兴的荧光剂,是具有抗光漂白性和环境友好性的生物相容性纳米颗粒,有望用于未来的体外生物成像研究。系统地研究了制备平均水动力直径低于 200nm 的胶束纳米结构的实验参数,以确保在生理介质中具有胶体稳定性,同时保持包封碳点的光学发光性能。采用光学和形态学技术对这些胶束纳米结构进行了全面的理化特性表征。此外,通过与羟基磷灰石纳米颗粒的结合实验评估了它们对骨组织主要无机成分的结合亲和力,表明它们具有显著的主动骨靶向潜力。这些制剂纳米结构有望为未来癌症患者的骨骼相关并发症提供新的治疗干预措施。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/48d1/11123821/86fb329293f3/molecules-29-02367-g002.jpg

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