School of Pharmacy, University of Jordan, Queen Rania Street, Amman, Jordan.
School of Pharmacy, AL-Zaytoonah University of Jordan, Amman, Jordan.
Asian Pac J Cancer Prev. 2023 Mar 1;24(3):977-989. doi: 10.31557/APJCP.2023.24.3.977.
The study aimed to examine rutin micelles of advanced superlative dual cytotoxicity-antiinflammtion bioefficacies in substantially novel submicro-nanoaffinities vs. both the raw rutin and reference proapoptotic cisplatin.
Antiproliferative capabilities of rutin, benzoic acid (BA) and triazolofluoroqunolone (TFQ) derivatives were reported; hence chemosensitizing effects of rutin or its polymeric micelles (of improved solubility and bioavailability via direct dissolution using the amphiphilic copolymer Pluronic P123) in co-incubations with 5 BAs or 3 TFQ derivatives in a panel of 6 cancer cell lines were verified.
Rutin loading in micelles was achieved with a loading efficiency of 59.5 ± 2.9%. The particle size of the micelles was found to be 18 ± 2 nm. Though Rutin loaded nanomicelles were of minimal DPPH radical scavenging activity; they had nitrogen oxide (NO) radical scavenging activity in lipopolysaccharide-induced RAW264.7 macrophages with equipotency to indomethacin (IC50 values (µM) 73.03 vs. 60.88; p=0.057). Remarkably nano-micelle formulation of rutin was proved of significantly more potent antineoplastic bioactivity with submicro-nanomolar affinities in the 6 cancer cell lines vs. both free rutin's and cisplatin's (except A549 lung cancer cell line). Rrutin nanomicelles chemo-sensitized all selected 8 cotreatments with BA derivatives and TFQs and, thus reducing the dose used against breast cancer MCF7 cells to submicro-nanomolar affinities of greater potencies than cisplatin's. Except for Triazolo-4-anisidine cipro butyl acid in PANC1, 2-Amino-3,5-Di iodo BA in A375 and 4-Nitrophenol in A549 incubations; rutin loaded nanomicelles chemosensitized 7/8 cotreating selected benzoic acid (BAs) derivatives and TFQs and chemosensitized pancreatic PANC1, skin A375 and lung A549 cancer cell lines, thus reducing the dose to submicro-nanomolar affinities of greater potencies than cisplatin's. Rutin loaded nanomicelles chemosensitize 6/8 cotreating selected benzoic acid (BA) derivatives and TFQs (except for 2-Amino-5-Bromo Benzoic Acid and Triazolo-4-anisidine cipro butyl acid), thus reducing the dose used against resistant CACO2 colorectal cancer cells.
本研究旨在考察芦丁胶束在亚微米-纳米亲和力方面的先进超级双重细胞毒性-抗炎生物功效，与芦丁和参考促凋亡顺铂相比，具有显著新颖的亚微观-纳米亲和力。
报道了芦丁、苯甲酸（BA）和三唑氟喹诺酮（TFQ）衍生物的抗增殖能力；因此，通过使用两亲性共聚物 Pluronic P123 直接溶解来提高溶解度和生物利用度，研究了芦丁或其聚合物胶束（通过直接溶解来提高溶解度和生物利用度）在与 5 种 BA 或 3 种 TFQ 衍生物共孵育时对 6 种癌细胞系的化学增敏作用。
芦丁在胶束中的载药量为 59.5%±2.9%。胶束的粒径为 18nm±2nm。虽然芦丁负载纳米胶束的 DPPH 自由基清除活性最小；但它们在脂多糖诱导的 RAW264.7 巨噬细胞中具有一氧化氮（NO）自由基清除活性，与吲哚美辛相当（IC50 值（µM）为 73.03 与 60.88；p=0.057）。值得注意的是，芦丁纳米胶束在 6 种癌细胞系中的抗肿瘤生物活性明显更强，具有亚微米-纳米亲和力，比游离芦丁和顺铂（除 A549 肺癌细胞系外）更有效。芦丁纳米胶束化学增敏了所有选定的 8 种 BA 衍生物和 TFQs 的共处理，从而将针对乳腺癌 MCF7 细胞的剂量降低至亚微米-纳米亲和力，其效力强于顺铂。除了 PANC1 中的三唑-4-茴香酸西布曲明丁酸、A375 中的 2-氨基-3,5-二碘苯甲酸和 A549 中的 4-硝基苯酚孵育外；芦丁负载纳米胶束化学增敏了 7/8 种选定的苯甲酸（BA）衍生物和 TFQs 的共处理，并化学增敏了胰腺 PANC1、皮肤 A375 和肺 A549 癌细胞系，从而将剂量降低至亚微米-纳米亲和力，其效力强于顺铂。芦丁负载纳米胶束化学增敏了 6/8 种选定的苯甲酸（BA）衍生物和 TFQs（除 2-氨基-5-溴苯甲酸和三唑-4-茴香酸西布曲明丁酸外），从而降低了针对耐药性 CACO2 结肠癌细胞的剂量。
