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用于靶向治疗结直肠癌的透明质酸-阿霉素纳米颗粒。

Hyaluronic acid-doxorubicin nanoparticles for targeted treatment of colorectal cancer.

作者信息

Pan Daniel C, Krishnan Vinu, Salinas Alyssa K, Kim Jayoung, Sun Tao, Ravid Sagi, Peng Kevin, Wu Debra, Nurunnabi Md, Nelson Jeffery A, Niziolek Zachary, Guo Junling, Mitragotri Samir

机构信息

School of Engineering & Applied Sciences, Harvard University Wyss Institute of Biologically Inspired Engineering Cambridge Massachusetts USA.

Faculty of Arts and Sciences, Division of Sciences Harvard University Cambridge Massachusetts USA.

出版信息

Bioeng Transl Med. 2020 May 28;6(1):e10166. doi: 10.1002/btm2.10166. eCollection 2021 Jan.

Abstract

Colorectal cancer, common in both men and women, occurs when tumors form in the linings of the colon. Common treatments of colorectal cancer include surgery, chemotherapy, and radiation therapy; however, many colorectal cancer treatments often damage healthy tissues and cells, inducing severe side effects. Conventional chemotherapeutic agents such as doxorubicin (Dox) can be potentially used for the treatment of colorectal cancer; however, they suffer from limited targeting and lack of selectivity. Here, we report that doxorubicin complexed to hyaluronic acid (HA) (HA-Dox) exhibits an unusual behavior of high accumulation in the intestines for at least 24 hr when injected intravenously. Intravenous administrations of HA-Dox effectively preserved the mucosal epithelial intestinal integrity in a chemical induced colon cancer model in mice. Moreover, treatment with HA-Dox decreased the expression of intestinal apoptotic and inflammatory markers. The results suggest that HA-Dox could effectively inhibit the development of colorectal cancer in a safe manner, which potentially be used a promising therapeutic option.

摘要

结直肠癌在男性和女性中都很常见,它发生于结肠内壁形成肿瘤时。结直肠癌的常见治疗方法包括手术、化疗和放疗;然而,许多结直肠癌治疗方法常常会损害健康组织和细胞,引发严重的副作用。传统化疗药物如阿霉素(Dox)可潜在用于治疗结直肠癌;然而,它们存在靶向性有限和缺乏选择性的问题。在此,我们报告,与透明质酸(HA)复合的阿霉素(HA-Dox)静脉注射后在肠道中表现出至少24小时的异常高蓄积行为。在化学诱导的小鼠结肠癌模型中,静脉注射HA-Dox有效地维持了肠道黏膜上皮的完整性。此外,HA-Dox治疗降低了肠道凋亡和炎症标志物的表达。结果表明,HA-Dox可以安全有效地抑制结直肠癌的发展,有望成为一种有前途的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ae8/7823125/98633d8eaf71/BTM2-6-e10166-g001.jpg

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