Hadad Elad, Rudnick-Glick Safra, Itzhaki Ella, Avivi Matan Y, Grinberg Igor, Elias Yuval, Margel Shlomo
Department of Chemistry, Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel.
The Mina and Everard Goodman Faculty of Life Sciences, Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel.
Polymers (Basel). 2020 Dec 16;12(12):2996. doi: 10.3390/polym12122996.
Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.
类蛋白是通过氨基酸的热逐步增长聚合制备的无毒可生物降解聚合物。在此，合成了基于D-精氨酸、甘氨酸和L-天冬氨酸的P(RGD)类蛋白和类蛋白纳米胶囊（NCs），并对其进行靶向肿瘤治疗的表征。阿霉素（Dox）是一种用于治疗多种癌症的化疗药物，因其副作用而闻名，在自组装过程中被包封以形成Dox/P(RGD) NCs。此外，肿瘤坏死因子相关凋亡诱导配体（TRAIL）可在大多数肿瘤细胞中引发凋亡，但会快速被酶降解，通过与中空P(RGD) NCs共价结合而得以稳定。还研究了聚乙二醇（PEG）缀合的效果。对CAOV-3卵巢癌细胞的细胞毒性测试表明，Dox/P(RGD)和TRAIL-P(RGD) NCs与游离Dox和TRAIL一样有效，细胞活力分别为2%和10%，而聚乙二醇化的NCs效果较差。载药P(RGD) NCs可实现控释，减少副作用，从而改善治疗效果。
