title: Solid Tumor Therapy Using a Cannon and Pawn Combination Strategy.
abstract: Nanocarrier-based anti-tumor drugs hold great promise for reducing side effects and improving tumor-site drug retention in the treatment of solid tumors. However, therapeutic outcomes are still limited, primarily due to a lack of drug penetration within most tumor tissues. Herein, we propose a strategy using a nanocarrier-based combination of vascular disrupting agents (VDAs) and cytotoxic drugs for solid tumor therapy. Specifically, combretastatin A-4 (CA4) serves as a "cannon" by eradicating tumor cells at a distance from blood vessels; concomitantly, doxorubicin (DOX) serves as a "pawn" by killing tumor cells in close proximity to blood vessels. This "cannon and pawn" combination strategy acts without a need to penetrate every tumor cell and is expected to eliminate all tumor cells in a solid tumor. In a murine C26 colon tumor model, this strategy proved effective in eradicating greater than 94% of tumor cells and efficiently inhibited tumor growth with a weekly injection. In large solid tumor models (C26 and 4T1 tumors with volumes of approximately 250 mm(3)), this strategy also proved effective for inhibiting tumor growth. These results showing remarkable inhibition of tumor growth provide a valuable therapeutic choice for solid tumor therapy.
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;
authors.forename: Wantong
authors.initials: W
authors.lastname: Song
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: 2. Department of Chemistry, Northeast Normal University, Changchun, 130021, PR China;
authors.forename: Xue
authors.initials: X
authors.lastname: Wen
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;; 3. University of Chinese Academy of Sciences, Beijing, 100039, PR China.
authors.forename: Shixian
authors.initials: S
authors.lastname: Lv
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;; 3. University of Chinese Academy of Sciences, Beijing, 100039, PR China.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 2. Department of Chemistry, Northeast Normal University, Changchun, 130021, PR China;
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Deng
authors.affiliation: 1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, PR China;
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination / Q000379:methods; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D013267:Stilbenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D013267:Stilbenes; D004317:Doxorubicin; C058728:fosbretabulin
keywords: combination; cytotoxic drugs; nanocarrier; tumor therapy.; vascular disrupting agents