title: Inhibiting Solid Tumor Growth In Vivo by Non-Tumor-Penetrating Nanomedicine.
abstract: Nanomedicine (NM) cannot penetrate deeply into solid tumors, which is partly attributed to the heterogeneous microenvironment and high interstitial fluid pressure of solid tumors. To improve NM efficacy, there has been tremendous effort developing tumor-penetrating NMs by miniaturizing NM sizes or controlling NM surface properties. But progress along the direction of developing tumor penetrating nanoparticle has been slow and improvement of the overall antitumor efficacy has been limited. Herein, a novel strategy of inhibiting solid tumor with high efficiency by dual-functional, nontumor-penetrating NM is demonstrated. The intended NM contains 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a vascular-disrupting agent, and doxorubicin (DOX), a cytotoxic drug. Upon arriving at the target tumor site, sustained release of DMXAA from NMs results in disruption of tumor vessel functions, greatly inhibiting the interior tumor cells by cutting off nutritional supply. Meanwhile, the released DOX kills the residual cells at the tumor exterior regions. The in vivo studies demonstrate that this dual-functional, nontumor penetrating NM exhibits superior anticancer activity, revealing an alternative strategy of effective tumor growth inhibition.
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Wantong
authors.initials: W
authors.lastname: Song
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory Animal Center, Jilin University, Changchun, 130012, China.
authors.forename: Huaiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Laboratory of Computer-Aided Drug Design and Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000067493:Dynamic Light Scattering; D005260:Female; D006801:Humans; D057446:Hydrodynamics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D004317:Doxorubicin
keywords: chemotherapy; drug combination; nanomedicine; tumor penetration; vascular-disrupting agent