Materials Chemistry Laboratory, Department of Chemistry, School of Natural Sciences, Shiv Nadar University, Delhi-NCR 201314, India.
Department of Life Sciences, School of Natural Sciences, Shiv Nadar University, Delhi-NCR 201314, India.
ACS Appl Bio Mater. 2022 Jul 18;5(7):3438-3451. doi: 10.1021/acsabm.2c00373. Epub 2022 Jun 27.
Nanodiamonds (NDs) are increasingly being assessed as potential candidates for drug delivery in cancer cells and they hold great promise in overcoming the side effects of traditional chemotherapeutics. In the current work, carboxylic acid functionalized nanodiamonds (ND-COOH) were covalently modified with poly(amidoamine) dendrimer (PAMAM) to form amine-terminated nanodiamonds (NP). Unlike ND-COOH, the chemically modified nanodiamond platform NP revealed a pH-independent aqueous dispersion stability, enhancing its potential as an effective carrier. Physical encapsulation of poorly water soluble cabazitaxel (CTX) drug on NP formed ND-PAMAM-CTX (NPC) nanoconjugates and substantially reduced the size of CTX from micrometer to nanometer. CTX was localized within the pores of nanoparticle aggregates and the cavities of the PAMAM dendrimer, thus facilitating the loaded drug's controlled and sustained release. NPC's cumulative CTX release efficiency was determined to be ∼95% at pH 4 after 96 h. A high cellular uptake of NPC both within the cytoplasm and nucleus of U87 cells is confirmed, accounting for a reduced IC value (1 nM). Both the cell cycle and Western blot analyses confirmed enhanced cell death and suppressed tubulin protein expression in NPC-treated cells. A significantly high inhibition to cell division with early apoptosis and reduced metastasis demonstrates the effective loading of CTX dosages on the nanocarrier. The present work highlights the potential of a newly designed nanocarrier NP as an efficient nanocargo for cellular delivery applications and may provide future insights to treat one of the most aggressive tumors in neuro-oncological research, glioblastoma multiforme (GBM).
纳米金刚石（NDs）作为癌症细胞中药物输送的潜在候选物，越来越受到关注，它们在克服传统化疗药物的副作用方面具有很大的潜力。在目前的工作中，羧酸功能化纳米金刚石（ND-COOH）通过聚酰胺胺树枝状大分子（PAMAM）进行了共价修饰，形成了胺端纳米金刚石（NP）。与 ND-COOH 不同，化学修饰后的纳米金刚石平台 NP 表现出 pH 值独立的水性分散稳定性，增强了其作为有效载体的潜力。将疏水性差的卡巴他赛（CTX）药物物理包封在 NP 上形成了 ND-PAMAM-CTX（NPC）纳米缀合物，使 CTX 的尺寸从微米级减小到纳米级。CTX 被定位在纳米颗粒聚集体的孔和 PAMAM 树枝状大分子的空腔内，从而促进了载药的控制和持续释放。在 pH 值为 4 时，NPC 在 96 小时后测定的 CTX 累积释放效率约为 95%。研究证实 NPC 在 U87 细胞的细胞质和细胞核内都具有较高的细胞摄取率，从而降低了 IC 值（1 nM）。细胞周期和 Western blot 分析均证实 NPC 处理后的细胞死亡增加，微管蛋白表达受到抑制。NPC 可显著抑制细胞分裂，诱导早期凋亡，降低转移，证明纳米载体有效负载了 CTX 剂量。本研究强调了新型纳米载体 NP 作为一种有效的细胞内递送应用的纳米载体的潜力，并可能为治疗神经肿瘤学研究中最具侵袭性的肿瘤之一——多形性胶质母细胞瘤（GBM）提供新的思路。
