Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Dist: Dhule, Shirpur 425405, MS, India.
Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Dist: Dhule, Shirpur 425405, MS, India; Department of Pharmaceutical Quality Assurance, H. R. Patel Institute of Pharmaceutical Education and Research, Dist: Dhule, Shirpur 425405, MS, India.
Int J Biol Macromol. 2024 Feb;259(Pt 2):129325. doi: 10.1016/j.ijbiomac.2024.129325. Epub 2024 Jan 12.
Hepatocellular carcinoma (HPTC) currently ranks as the third leading cause of cancer-related mortality, necessitating an advanced formulation strategy. Recently, lactoferrin (Lf) has been utilized as a specific targeting ligand in HPTC due to its high specificity towards the asialoglycoprotein receptor expressed in cancer cells. Therefore, we present the fabrication of an Lf-decorated carboxymethyl dextran-encased chitosan-coated europium metal-organic framework-based nanobioconjugate (Lf-CMD-CS-CUR@Eu-MOF) for targeted curcumin (CUR) delivery. Briefly, CUR was loaded into Eu-MOF, followed by coating cationic 'CS' on the CUR@Eu-MOF surface. Simultaneously, Lf-decorated CMD was prepared via an esterification reaction. Subsequently, Lf-CMD-CS-CUR@Eu-MOF was synthesized using the Maillard reaction. Various spectral characterizations, drug entrapment, drug content, in vitro drug release, biocompatibility and cell cytotoxicity studies were performed. It exhibited an entrapment efficiency of 88.87 ± 2.1 %, a drug content of 3.45 ± 0.98 %, and a drug loading rate of 34.85 ± 0.6 mg/g. Furthermore, the Lf-CMD-CS-CUR@Eu-MOF exhibits excellent biocompatibility with normal cells. The in vitro dissolution study confirmed a release of 78.12 % of 'CUR' in pH 5.8 phosphate buffer (over 120 h), attributed to the controlled release rate by the 'CS' coating on the surface of CUR@Eu-MOF. The BEL-7402 cell line showed concentration-dependent toxicity of nanobioconjugate to cancerous cells. Therefore, when 'Lf' is surface-decorated onto an appropriate polymeric material, it gains the capability to function as a carrier for transporting 'CUR' to the precise target site within HPTC. In conclusion, Lf-CMD incorporated CS-coated Eu-MOF can provide a promising approach for targeted drug delivery in HPTC management.
肝细胞癌（Hepatocellular carcinoma，HPTC）目前是癌症相关死亡的第三大主要原因，因此需要一种先进的制剂策略。由于乳铁蛋白（Lactoferrin，Lf）对癌细胞表达的唾液酸糖蛋白受体具有高度特异性，因此最近已将其用作 HPTC 的特定靶向配体。因此，我们提出了一种乳铁蛋白修饰的羧甲基葡聚糖包裹壳聚糖包裹的铕金属有机骨架纳米生物缀合物（Lf-CMD-CS-CUR@Eu-MOF）的制备方法，用于靶向姜黄素（Curcumin，CUR）的递送。简而言之，将 CUR 装载到 Eu-MOF 中，然后在 CUR@Eu-MOF 表面涂覆阳离子“CS”。同时，通过酯化反应制备了乳铁蛋白修饰的 CMD。随后，通过美拉德反应合成了 Lf-CMD-CS-CUR@Eu-MOF。进行了各种光谱特性、药物包封、药物含量、体外药物释放、生物相容性和细胞细胞毒性研究。结果表明，其包封效率为 88.87±2.1%，药物含量为 3.45±0.98%，药物载药量为 34.85±0.6mg/g。此外，Lf-CMD-CS-CUR@Eu-MOF 对正常细胞具有良好的生物相容性。体外溶解研究证实，在 pH5.8 磷酸盐缓冲液中（超过 120 小时），“CUR”的释放量为 78.12%，这归因于“CS”在 CUR@Eu-MOF 表面的控释率。BEL-7402 细胞系表现出纳米生物缀合物对癌细胞的浓度依赖性毒性。因此，当“Lf”表面修饰在适当的聚合物材料上时，它能够作为载体将“CUR”运送到 HPTC 中的精确靶位。总之，Lf-CMD 掺入 CS 涂层的 Eu-MOF 可为 HPTC 管理中的靶向药物递送提供一种有前途的方法。
