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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
Source PublicationAdvanced Healthcare Materials
ISSN2192-2640
Volume5Issue:22Pages:2872-2881
Abstract

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.

KeywordDoxorubicin Gold Nanorods Novel Drug Delivery Systems Trastuzumab Tumor Microenvironment And Modification
SubtypeArticle
WOS HeadingsScience & Technology ; Technology
DOI10.1002/adhm.201600528
Indexed BySCI
Language英语
WOS KeywordTUMOR INTERSTITIAL FLUID ; IN-VIVO ; EXTRACELLULAR-MATRIX ; DRUG-DELIVERY ; CANCER-CELLS ; SOLID TUMORS ; NANOPARTICLES ; PENETRATION ; MICROENVIRONMENT ; TISSUE
WOS Research AreaEngineering ; Science & Technology - Other Topics ; Materials Science
WOS SubjectEngineering, Biomedical ; Nanoscience & Nanotechnology ; Materials Science, Biomaterials
Funding OrganizationNational 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 IDWOS:000388999900004
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/21824
Collection生化工程国家重点实验室
Affiliation1.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
Recommended Citation
GB/T 7714
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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