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具有可控释放吡非尼酮和超声靶向微泡破坏(UTMD)功能的可生物降解、pH 敏感的中空介孔有机硅纳米颗粒(HMON)用于胰腺癌治疗。

Biodegradable, pH-Sensitive Hollow Mesoporous Organosilica Nanoparticle (HMON) with Controlled Release of Pirfenidone and Ultrasound-Target-Microbubble-Destruction (UTMD) for Pancreatic Cancer Treatment.

机构信息

Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201600, P.R. China.

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P.R. China.

出版信息

Theranostics. 2019 Aug 14;9(20):6002-6018. doi: 10.7150/thno.36135. eCollection 2019.

Abstract

The dense extracellular matrix (ECM) and hypovascular networks were often found in solid pancreatic tumors form an impenetrable barrier, leading to limited uptake of chemotherapeutics and thus undesirable treatment outcomes. : A biodegradable nanoplatform based on hollow mesoporous organosilica nanoparticle (HMON) was designed as an effective delivery system for pirfenidone (PFD) to overcome the challenges in pancreatic tumor treatment. By varying pH producing a mildly acidic environment to emulate tumor cells, results in cleavage of the acetal bond between HMON nanoparticle and gating molecular, gemcitabine (Gem), enabling its controlled release. : The and immunocytochemistry evaluations demonstrated an excellent ECM regulation efficacy of the nanoplatform and therefore the improved penetration of drug into the cells. The technique employed was especially enhanced when mediated with ultrasound target microbubble destruction (UTMD). Evaluations culminated with pancreatic cancer bearing mice and demonstrated therapeutic efficacy, good biodegradability, and negligible systemic toxicity. : the designed Gem gated biodegradable nanosystem is expected to provide an alternative way of improving antitumor efficacy by down-regulation of ECM levels and offers a passive-targeted therapy for pancreatic cancer treatment.

摘要

致密的细胞外基质 (ECM) 和乏血管网络通常存在于实体胰腺肿瘤中,形成了一个难以穿透的屏障,导致化疗药物摄取有限,从而导致不理想的治疗效果。:一种基于中空介孔有机硅纳米粒子 (HMON) 的可生物降解纳米平台被设计为一种有效的比非尼酮 (PFD) 递送系统,以克服胰腺肿瘤治疗中的挑战。通过改变 pH 值产生模拟肿瘤细胞的微酸性环境,导致 HMON 纳米颗粒与门控分子吉西他滨 (Gem) 之间的缩醛键断裂,实现其控制释放。:免疫细胞化学评估表明,该纳米平台具有出色的 ECM 调节功效,从而提高了药物进入细胞的渗透能力。当与超声靶向微泡破坏 (UTMD) 结合使用时,该技术得到了特别增强。最终对患有胰腺癌的小鼠进行了评估,并证明了该纳米系统具有治疗效果、良好的生物降解性和可忽略的全身毒性。:设计的 Gem 门控可生物降解纳米系统有望通过下调 ECM 水平提供一种提高抗肿瘤疗效的替代方法,并为胰腺癌治疗提供被动靶向治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1999/6735371/f4011c6af7f8/thnov09p6002g001.jpg

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