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Self-Assembling Monomeric Nucleoside Molecular Nanoparticles Loaded with 5-FU Enhancing Therapeutic Efficacy against Oral Cancer
ACS Nano ( IF 15.8 ) Pub Date : 2015-09-14 00:00:00 , DOI: 10.1021/acsnano.5b04520 Hang Zhao 1, 2 , Hui Feng 1, 3 , Dongjuan Liu 1 , Jiang Liu 1, 2 , Ning Ji 1 , Fangman Chen 1 , Xiaobo Luo 1 , Yu Zhou 1 , Hongxia Dan 1 , Xin Zeng 1 , Jing Li 1 , Congkui Sun 1 , Jinyu Meng 1 , Xiaojie Ju 4 , Min Zhou 1 , Hanshuo Yang 5 , Longjiang Li 1 , Xinhua Liang 1 , Liangyin Chu 4 , Lu Jiang 1 , Yang He 2 , Qianming Chen 1
ACS Nano ( IF 15.8 ) Pub Date : 2015-09-14 00:00:00 , DOI: 10.1021/acsnano.5b04520 Hang Zhao 1, 2 , Hui Feng 1, 3 , Dongjuan Liu 1 , Jiang Liu 1, 2 , Ning Ji 1 , Fangman Chen 1 , Xiaobo Luo 1 , Yu Zhou 1 , Hongxia Dan 1 , Xin Zeng 1 , Jing Li 1 , Congkui Sun 1 , Jinyu Meng 1 , Xiaojie Ju 4 , Min Zhou 1 , Hanshuo Yang 5 , Longjiang Li 1 , Xinhua Liang 1 , Liangyin Chu 4 , Lu Jiang 1 , Yang He 2 , Qianming Chen 1
Affiliation
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Conventional oligonucleotide based drug delivery systems suffer from lengthy synthetic protocols, high cost, and poor chemical or enzymatic stability under certain circumstances. Canonical free individual nucleosides cannot form stable nanostructures in aqueous solution as drug vehicles. Here, we report the development of a monomeric self-assembled nucleoside nanoparticle (SNNP) into an efficient drug delivery system which has currently no parallel in such field. This was achieved using a l-configurational pyrimido[4,5-d]pyrimidine nucleoside building block that can form robust discrete nanoparticles in just one step with water as the sole solvent. Its high biocompatibility and low toxicity was demonstrated in vitro and in vivo. In mouse xenograft model of oral squamous cell carcinoma (OSCC), SNNP loaded with 5-fluoro-uracile (5-FU-SNNP) remarkably retarded the tumor growth compared with free 5-FU, albeit SNNP alone showed no antitumor effect. The stability in blood circulation and the effective concentration of 5-FU in tumor tissue were increased upon the loading with SNNP. TUNEL and immunohistochemistry analyses further indicated that the superior in vivo antitumor efficacy of 5-FU-SNNP compared to free 5-FU was associated with an enhanced degree of inhibition of cell proliferation and stimulation of cell apoptosis. Furthermore, SNNP alleviated the toxic side effects of 5-FU. These findings suggested that when loaded with SNNP, 5-FU has better antitumor efficacy and lower side effects, indicating that SNNP can efficiently act as a readily accessible, robust, biocompatible and low-toxic nanobiomaterial which may find wide therapeutic applications clinically in the future.
中文翻译：
自组装单体核苷分子纳米粒子负载5-FU增强对口腔癌的治疗功效。
常规的基于寡核苷酸的药物递送系统在某些情况下具有冗长的合成方案，高成本以及不良的化学或酶稳定性。不含规范成分的单个核苷不能在水溶液中形成稳定的纳米结构作为药物媒介物。在这里，我们报告了单体自组装核苷纳米粒子（SNNP）的发展成一种有效的药物输送系统，目前在该领域尚无类似产品。这是使用1-构型嘧啶并[4,5- d ]嘧啶核苷结构单元实现的，该结构单元可以在仅一步的情况下以水为唯一溶剂形成坚固的离散纳米颗粒。在体外和体内证明了其高生物相容性和低毒性。在小鼠口腔鳞状细胞癌（OSCC）异种移植模型中，与游离5-FU相比，负载有5-氟尿嘧啶（5-FU-SNNP）的SNNP显着延迟了肿瘤的生长，尽管仅SNNP没有显示出抗肿瘤作用。加载SNNP后，血液循环的稳定性和肿瘤组织中5-FU的有效浓度增加。TUNEL和免疫组化分析进一步表明，在体内优越5-FU-SNNP相对于游离5-FU的抗肿瘤功效与细胞增殖抑制作用和细胞凋亡刺激作用增强有关。此外，SNNP减轻了5-FU的毒副作用。这些发现表明，5-FU负载有SNNP时具有更好的抗肿瘤功效和较低的副作用，表明SNNP可以有效地用作易于获得，坚固，生物相容性和低毒性的纳米生物材料，在未来的临床中可能会找到广泛的治疗应用。
更新日期：2015-09-14
中文翻译：
自组装单体核苷分子纳米粒子负载5-FU增强对口腔癌的治疗功效。
常规的基于寡核苷酸的药物递送系统在某些情况下具有冗长的合成方案，高成本以及不良的化学或酶稳定性。不含规范成分的单个核苷不能在水溶液中形成稳定的纳米结构作为药物媒介物。在这里，我们报告了单体自组装核苷纳米粒子（SNNP）的发展成一种有效的药物输送系统，目前在该领域尚无类似产品。这是使用1-构型嘧啶并[4,5- d ]嘧啶核苷结构单元实现的，该结构单元可以在仅一步的情况下以水为唯一溶剂形成坚固的离散纳米颗粒。在体外和体内证明了其高生物相容性和低毒性。在小鼠口腔鳞状细胞癌（OSCC）异种移植模型中，与游离5-FU相比，负载有5-氟尿嘧啶（5-FU-SNNP）的SNNP显着延迟了肿瘤的生长，尽管仅SNNP没有显示出抗肿瘤作用。加载SNNP后，血液循环的稳定性和肿瘤组织中5-FU的有效浓度增加。TUNEL和免疫组化分析进一步表明，在体内优越5-FU-SNNP相对于游离5-FU的抗肿瘤功效与细胞增殖抑制作用和细胞凋亡刺激作用增强有关。此外，SNNP减轻了5-FU的毒副作用。这些发现表明，5-FU负载有SNNP时具有更好的抗肿瘤功效和较低的副作用，表明SNNP可以有效地用作易于获得，坚固，生物相容性和低毒性的纳米生物材料，在未来的临床中可能会找到广泛的治疗应用。
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