Department of Organic and Inorganic Chemistry, Science Centre, Federal University of Ceará, 60455-970 Fortaleza, CE, Brazil.
Department of Pharmacy, Faculty of Pharmacy, Odontology and Nursing, Federal University of Ceará, 60430-372 Fortaleza, CE, Brazil.
Bioorg Med Chem Lett. 2020 Oct 15;30(20):127469. doi: 10.1016/j.bmcl.2020.127469. Epub 2020 Aug 6.
The pentacyclic triterpene 3β,6β,16β-tri-hydroxilup-20(29)-ene is a natural product produced by the Brazilian medicinal plant Combretum leprosum. Its cytotoxicity has been previously reported against breast cancer cell lines. The low water solubility of this natural product, that hampers its bioavailability, motivated the investigation of a new nanoparticle formulation containing the triterpene in order to improve its bioactivity. The triterpene was encapsulated in polycaprolactone (PCL) polymer by nanoprecipitation, producing homogenic nanoparticles with nanometer sizes (122.7 ± 2.06 nm), which were characterized by FT-IR, SEM imaging and DSC. The cytotoxicity (MTT method) of the nanoparticle containing the triterpene 1, besides the free natural product and the nanoparticle control (without 1), was assayed against three human tumor cell lines [human colon carcinoma line (HCT116), prostate (PC3) and glioblastoma (SNB19)] and the normal epithelial embryo kidney human cell line (Hek293T). The nanocarrier produced a significative effect in the cytotoxicity of the natural product in the nanoformulation (IC 0.11-0.26 µg mL) when compared with its free form (IC 1.07-1.44 µg mL). Additionally, higher selectivity of the triterpene to the tumor cells was found when it was encapsulated (SI 1.92-4.54) than in its free form (SI 0.42-0.56). In this case, the nanoencapsulated triterpene was more selective to PC3 (SI 3.33) and SNB19 (SI 4.54) tumor cells.
五环三萜 3β,6β,16β-三羟基齐墩果酸是一种由巴西药用植物 Combretum leprosum 产生的天然产物。其对乳腺癌细胞系的细胞毒性先前已有报道。由于该天然产物的水溶性低，限制了其生物利用度，因此研究了一种新的纳米颗粒制剂，其中包含该三萜，以提高其生物活性。该三萜通过纳米沉淀包封在聚己内酯（PCL）聚合物中，产生纳米尺寸（122.7±2.06nm）的均一纳米颗粒，通过傅里叶变换红外光谱（FT-IR）、扫描电子显微镜成像和差示扫描量热法（DSC）对其进行了表征。用纳米颗粒（MTT 法）测定了载有三萜 1 的纳米颗粒的细胞毒性，除了游离天然产物和纳米颗粒对照（不含 1）外，还测定了三萜对三种人类肿瘤细胞系[人结肠癌细胞系（HCT116）、前列腺癌细胞系（PC3）和神经胶质瘤细胞系（SNB19）]和正常上皮胚肾人细胞系（Hek293T）的细胞毒性。与游离形式相比（IC 0.11-0.26μg/mL），纳米载体在纳米制剂中显著提高了天然产物的细胞毒性（IC 0.11-0.26μg/mL）。此外，当三萜被包封时，对肿瘤细胞的选择性更高（SI 1.92-4.54），而游离形式时的选择性较低（SI 0.42-0.56）。在这种情况下，纳米包封的三萜对 PC3（SI 3.33）和 SNB19（SI 4.54）肿瘤细胞的选择性更高。
