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Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales
Liu, Shan1,2; Wei, Wei1; Xie, Bo1; Yue, Hua1; Ni, Dezhi1,2; Bao, Yali1; Ma, Guanghui1,3; Su, Zhiguo G.1
2016-11-23
发表期刊Advanced Healthcare Materials
ISSN2192-2640
卷号5期号:22页码:2872-2881
摘要

In contrast to traditional strategies based on external driving forces, an internal path for intratumoral delivery is explored by degrading the tumor microenvironment component hyaluronan. Natural hyaluronidase PH20 and constructed long-acting PH20-Fc have been used to achieve this objective. It has been then evaluated how these agents facilitate the diffusion of the following typical therapeutic agents varying in nanoscales: doxorubicin (approximate to 1.5 x 1.0 x 0.7 nm) chemotherapy, trastuzumab (10-15 nm) biotherapy, and gold nanorod (approximate to 100 x 35 nm) thermotherapy. In traditional 2D cultures, PH20 and PH20-Fc have little influence on cytotoxicity due to lack of a tumor microenvironment. However, the cytotoxicities of the three therapeutic agents in 3D tumor spheroids are all enhanced by PH20 or PH20-Fc because hyaluronan degradation facilitates therapeutic penetration and accumulation. Furthermore, in vivo evaluations reveal that the significantly prolonged circulation time of PH20-Fc leads to accumulation in the tumor and subsequent hyaluronan degradation. Consequently, PH20-Fc coadministration further inhibits tumor growth. The performance of PH20-Fc varies for the three therapeutic agents due to their different nanoscales. Trastuzumab benefits most from combination with PH20-Fc. The results provide here novel insights that can aid in the development of more effective hyaluronidase-based therapeutic systems.

关键词Doxorubicin Gold Nanorods Novel Drug Delivery Systems Trastuzumab Tumor Microenvironment And Modification
文章类型Article
WOS标题词Science & Technology ; Technology
DOI10.1002/adhm.201600528
收录类别SCI
语种英语
关键词[WOS]TUMOR INTERSTITIAL FLUID ; IN-VIVO ; EXTRACELLULAR-MATRIX ; DRUG-DELIVERY ; CANCER-CELLS ; SOLID TUMORS ; NANOPARTICLES ; PENETRATION ; MICROENVIRONMENT ; TISSUE
WOS研究方向Engineering ; Science & Technology - Other Topics ; Materials Science
WOS类目Engineering, Biomedical ; Nanoscience & Nanotechnology ; Materials Science, Biomaterials
项目资助者National Science and Technology Major Projects for "Major New Drugs Innovation and Development"(2014ZX09102045-004) ; Beijing Nova Program(Z141102001814066) ; Center for Mesoscience, Institure of Process Engineering, Chinese Academy of Sciences(COM2015A0006)
WOS记录号WOS:000388999900004
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/21824
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, State Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Peoples R China
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Liu, Shan,Wei, Wei,Xie, Bo,et al. Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales[J]. Advanced Healthcare Materials,2016,5(22):2872-2881.
APA Liu, Shan.,Wei, Wei.,Xie, Bo.,Yue, Hua.,Ni, Dezhi.,...&Su, Zhiguo G..(2016).Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales.Advanced Healthcare Materials,5(22),2872-2881.
MLA Liu, Shan,et al."Breaching the Hyaluronan Barrier with PH20-Fc Facilitates Intratumoral Permeation and Enhances Antitumor Efficiency: A Comparative Investigation of Typical Therapeutic Agents in Different Nanoscales".Advanced Healthcare Materials 5.22(2016):2872-2881.
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