title: Hyaluronidase To Enhance Nanoparticle-Based Photodynamic Tumor Therapy.
abstract: Photodynamic therapy (PDT) is considered as a safe and selective way to treat a wide range of cancers as well as nononcological disorders. However, as oxygen is required in the process of PDT, the hypoxic tumor microenvironment has largely limited the efficacy of PDT to treat tumors especially those with relatively large sizes. To this end, we uncover that hyaluronidase (HAase), which breaks down hyaluronan, a major component of extracellular matrix (ECM) in tumors, would be able to enhance the efficacy of nanoparticle-based PDT for in vivo cancer treatment. It is found that the administration of HAase would lead to the increase of tumor vessel densities and effective vascular areas, resulting in increased perfusion inside the tumor. As a result, the tumor uptake of nanomicelles covalently linked with chlorine e6 (NM-Ce6) would be increased by ∼2 folds due to the improved "enhanced permeability and retention" (EPR) effect, while the tumor oxygenation level also shows a remarkable increase, effectively relieving the hypoxia state inside the tumor. Those effects taken together offer significant benefits in greatly improving the efficacy of PDT delivered by nanoparticles. Taking advantage of the effective migration of HAase from the primary tumor to its drainage sentinel lymph nodes (SLNs), we further demonstrate that this strategy would be helpful to the treatment of metastatic lymph nodes by nanoparticle-based PDT. Lastly, both enhanced EPR effect of NM-Ce6 and relieved hypoxia state of tumor are also observed after systemic injection of modified HAase, proving its potential for clinical translation. Therefore, our work presents a new concept to improve the efficacy of nanomedicine by modulating the tumor microenvironment.
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gong
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Song
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Guangbao
authors.initials: G
authors.lastname: Yang
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University , Suzhou, Jiangsu 215123, China.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006821:Hyaluronoglucosaminidase / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D008823:Micelles; D006821:Hyaluronoglucosaminidase
keywords: Hyaluronidase; lymphatic metastasis; nanomedicine; photodynamic therapy; tumor microenvironment