Combretastatin A4 Nanodrug‐Induced MMP9 Amplification Boosts Tumor‐Selective Release of Doxorubicin Prodrug

Abstract

Tumor‐associated enzyme‐activated prodrugs can potentially improve the selectivity of chemotherapeutics. However, the paucity of tumor‐associated enzymes which are essential for prodrug activation usually limits the antitumor potency. A cooperative strategy that utilizes combretastatin A4 nanodrug (CA4‐NPs) and matrix metalloproteinase 9 (MMP9)‐activated doxorubicin prodrug (MMP9‐DOX‐NPs) is developed. CA4 is a typical vascular disrupting agent that can selectively disrupt immature tumor blood vessels and exacerbate the tumor hypoxia state. After treatment with CA4‐NPs, MMP9 expression can be significantly enhanced by 5.6‐fold in treated tumors, which further boosts tumor‐selective active drug release of MMP9‐DOX‐NPs by 3.7‐fold in an orthotopic 4T1 mammary adenocarcinoma mouse model. The sequential delivery of CA4‐NPs and MMP9‐DOX‐NPs exhibits enhanced antitumor efficacy with reduced systemic toxicity compared with the noncooperative controls.

Self-accelerating H2O2-responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors

“…In addition to serve as contrast agent for CT imaging, the TG-GVs effectively inhibited the growth of tumors in vivo . This nanoplatform may find application in effective tumor inhibition, especially for tumors deeply trapped in viscera or other tissues 69 - 72 .…”

Redox responsive nanoparticle encapsulating black phosphorus quantum dots for cancer theranostics

“…S15 ). As the ALT, AST, ALP, ALB and TP levels are usually closely associated with the functions of the liver and kidney of mice, while CREA and BUN relate to the function of the kidney [ 44 ], the results confirm that the treatment does not cause obvious hepatic or renal toxicity [ 45 , 46 ].…”

Neue Mitglieder der Chinesischen Akademie der Wissenschaften

“…Chen erforscht Schiff‐Base‐Katalysatoren für die Ringöffnungspolymerisation von Lactiden und anderen cyclischen Monomeren sowie biologisch abbaubare Polymere für biomedizinische Anwendungen, die Heilung von Knochenbrüchen, Wirkstoff‐ und Gentransporter, Hydrogele und die Industrialisierung von Polylactid als “grüner” Kunststoff. Er berichtete in einer Advanced‐Materials ‐Zuschrift kürzlich über eine Nanowirkstoff, der die MMP9‐Vervielfältigung induziert und die tumorselektive Doxorubicin‐Freisetzung bewirkt . Chen gehört den Beiräten von Macromolecular Bioscience , Advanced Therapeutics und Advanced Healthcare Materials an.…”