Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, P.R. China.
Department of Pharmacy, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, 210002, P.R. China.
Colloids Surf B Biointerfaces. 2022 Sep;217:112613. doi: 10.1016/j.colsurfb.2022.112613. Epub 2022 Jun 22.
To increase the solubility and targeting efficiency of curcumin (CCM) to tumors, transferrin (Tf)-CCM nanoparticles (NPs-CCM) with a CCM loading capacity of 5.2% were fabricated by Tf denaturation with hydrochloric acid, a denaturing agent, to open the hydrophobic cavity of Tf. The NPs-CCM were approximately 160 nm in size with a spherical shape. The solubility of the CCM in the nanoparticles was approximately 100,000 times greater than that of CCM alone (11 ng mL vs 1.11 mg mL, respectively). The changes in the fluorescence spectra of Tf and 1-(anilinon)-aphthalene-8-sulfonic acid (ANS) in the NP-CCM preparation indicated that the polarity of certain hydrophobic and hydrophilic groups of Tf changed. CCM treatment of A549 cells resulted in a decrease in the mitochondrial membrane potential (MMP) and induced apoptosis through mitochondrial dependence. CCM increased the expression of phosphorylated c-Jun N-terminal kinase (JNK), P38, and extracellular signal-regulated kinase (ERK) but had a weak effect on the expression of nonphosphorylated JNK, P38, and ERK, which showed that the mitogen-activated protein kinase signaling (MAPK) transduction pathway is involved in CCM-mediated apoptosis. The half maximal inhibitory concentration (IC) of NPs-CCM was higher than that of free CCM in A549 (16.41 ± 0.86 vs 12.51 ± 3.9 (μg mL), p = 0.036) and MCF-7 (9.31 ± 0.11 vs 2.44 ± 3.76 (μg mL), p < 0.0037) tumor cells, however the former had a greater tumor-targeting in vivo. Without the side effects of polyoxyethylene castor oil/ethanol as solvent, the hemolysis effect of NPs-CCM (0.05-1 mg mL) was notably lower than that of free CCM (p < 0.05). It was estimated that the half maximal lethal dose (LD) of NPs-CCM was approximately two times that of CCM (100 mg kg vs 50 mg kg), and the former had many advantages over that of free CCM in terms of lower toxicity and better targeting; thus, NPs-CCM can be administered at higher doses to acquire better antitumor effects than CCM alone, indicating that NPs-CCM are an effective and safe carrier for CCM delivery.
为了提高姜黄素（CCM）的溶解度和靶向效率，采用盐酸（一种变性剂）使转铁蛋白（Tf）变性，制备了载药量为 5.2%的 Tf-CCM 纳米粒子（NPs-CCM），以打开 Tf 的疏水性腔。NPs-CCM 的粒径约为 160nm，呈球形。与游离 CCM 相比，纳米粒子中 CCM 的溶解度约增加了 100,000 倍（分别为 11ng mL 与 1.11mg mL）。Tf 和 1-（苯胺基）-萘-8-磺酸（ANS）荧光光谱的变化表明 Tf 中某些疏水性和亲水性基团的极性发生了变化。CCM 处理 A549 细胞会导致线粒体膜电位（MMP）降低，并通过线粒体依赖性诱导细胞凋亡。CCM 增加了磷酸化 c-Jun N-末端激酶（JNK）、P38 和细胞外信号调节激酶（ERK）的表达，但对非磷酸化 JNK、P38 和 ERK 的表达影响较弱，表明丝裂原激活蛋白激酶信号转导途径（MAPK）参与了 CCM 介导的细胞凋亡。NPs-CCM 在 A549（16.41±0.86 与 12.51±3.9（μg mL），p=0.036）和 MCF-7（9.31±0.11 与 2.44±3.76（μg mL），p<0.0037）肿瘤细胞中的半数最大抑制浓度（IC）均高于游离 CCM，而前者在体内具有更好的肿瘤靶向性。与聚氧乙烯蓖麻油/乙醇作为溶剂的副作用相比，NPs-CCM（0.05-1mg mL）的溶血作用明显低于游离 CCM（p<0.05）。估计 NPs-CCM 的半最大致死剂量（LD）约为 CCM 的两倍（100mg kg 与 50mg kg），与游离 CCM 相比，前者在毒性较低和靶向性更好方面具有许多优势；因此，与单独使用 CCM 相比，NPs-CCM 可以以更高的剂量给药以获得更好的抗肿瘤效果，表明 NPs-CCM 是 CCM 递送的有效且安全的载体。
