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Tumor Starvation Induced Spatiotemporal Control over Chemotherapy for Synergistic Therapy
Author(s) -
Zhang MingKang,
Li ChuXin,
Wang ShiBo,
Liu Tao,
Song XianLin,
Yang XiaoQuan,
Feng Jun,
Zhang XianZheng
Publication year - 2018
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201803602
Subject(s) - tirapazamine , chemotherapy , starvation , hypoxia (environmental) , prodrug , glucose oxidase , radiation therapy , chemistry , cancer research , antimicrobial chemotherapy , biophysics , biochemistry , enzyme , medicine , biology , antibiotics , oxygen , organic chemistry , cytotoxicity , in vitro
By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation‐induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity‐decomposable calcium carbonate (CaCO 3 ) nanoparticles concurrently tethered by hyaluronic acid. This hybrid nanotherapeutic shows a strong tendency to accumulate in tumors postinjection due to the cooperation between passive and active targeting mechanisms. The GOD‐driven oxidation reaction deprives tumors of glucose for starvation therapy and concomitantly induces tumorous abnormality amplifications including elevated acidity and exacerbated hypoxia. Programmatically, the acidity amplification causes CaCO 3 decomposition, offering not only spatial control over the liberation of embedded TPZ just within tumors but also the temporal control over timely chemotherapy initiation to match the occurrence of hypoxia amplification and thus benefiting perfect synergism between starvation therapy and chemotherapy.