School of Materials Science and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India.
Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, India.
ACS Biomater Sci Eng. 2024 Oct 14;10(10):6377-6396. doi: 10.1021/acsbiomaterials.4c01289. Epub 2024 Sep 11.
Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li-Al (M/M)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M M (OH)][(A). (HO)], which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li-Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.
临床肿瘤学目前正面临着一个技术瓶颈，因为肿瘤的治疗耐药性正在迅速演变。虽然化疗中使用的药物对某种具有潜在临床应用的细胞死亡有效，但单独使用时，化疗诱导药物的效果受到几种内源性条件的限制，因此迫切需要控制机制。已经提出了一种使用 Li-Al（M/M）-基层状双氢氧化物（LDHs）家族的肿瘤靶向药物递送疗法，其通用化学式为[M M（OH）][（A）]。（HO)]，它完全可生物降解，并与 LDH 纳米载体与抗癌阿霉素（DOX）之间的治疗相互作用相结合。LDHs 中 Li 和 Al 的组成变化被用作纳米平台，为循环寿命、载药量、包封效率和肿瘤特异性摄取之间提供了功能平衡，以作为自调节治疗货物在细胞内释放。基于 DFT 的第一性原理分析已被用于研究 LDH 与 DOX 的键合和电子结构的相互作用，并评估其作为优越药物载体的能力和潜力。纳米制剂进入癌细胞后，通过溶酶体被带到细胞核，并且已经揭示了其作用机制途径。此外，在携带黑色素瘤的小鼠进行的体外和体内治疗评估表明，纳米制剂的尺寸效应可提高生物相容性和优异的协同抗癌活性。此外，通过在肿瘤部位下方放置可注射水凝胶，消除了传统化疗带来的严重毒性后果，并且通过应用各种标记物的蛋白质表达确认了药物的受控释放。然而，Li-Al 基 LDH 纳米载体为多功能纳米医学开辟了新的设计选择，通过持续药物递送，在癌症治疗中具有有趣的应用潜力。
