{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(6)"],"submitter":["Besse HC"],"pubmed_abstract":["The poor pharmacokinetics and selectivity of low-molecular-weight anticancer drugs contribute to the relatively low effectiveness of chemotherapy treatments. To improve the pharmacokinetics and selectivity of these treatments, the combination of a doxorubicin-glucuronide prodrug (DOX-propGA3) nanogel formulation and the liberation of endogenous β-glucuronidase from cells exposed to high-intensity focused ultrasound (HIFU) were investigated in vitro. First, a DOX-propGA3-polymer was synthesized. Subsequently, DOX-propGA3-nanogels were formed from this polymer dissolved in water using inverse mini-emulsion photopolymerization. In the presence of bovine β-glucuronidase, the DOX-propGA3 in the nanogels was quantitatively converted into the chemotherapeutic drug doxorubicin. Exposure of cells to HIFU efficiently induced liberation of endogenous β-glucuronidase, which in turn converted the prodrug released from the DOX-propGA3-nanogels into doxorubicin. β-glucuronidase liberated from cells exposed to HIFU increased the cytotoxicity of DOX-propGA3-nanogels to a similar extend as bovine β-glucuronidase, whereas in the absence of either bovine β-glucuronidase or β-glucuronidase liberated from cells exposed to HIFU, the DOX-propGA3-nanogels hardly showed cytotoxicity. Overall, DOX-propGA3-nanogels systems might help to further improve the outcome of HIFU-related anticancer therapy."],"journal":["Pharmaceutics"],"pagination":["E536"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7355552"],"repository":["biostudies-literature"],"pubmed_title":["A Doxorubicin-Glucuronide Prodrug Released from Nanogels Activated by High-Intensity Focused Ultrasound Liberated β-Glucuronidase."],"pmcid":["PMC7355552"],"pubmed_authors":["Hennink WE","Deckers R","Metselaar JM","Besse HC","Chen Y","Lammers T","Moonen CTW","Scheeren HW"],"additional_accession":[]},"is_claimable":false,"name":"A Doxorubicin-Glucuronide Prodrug Released from Nanogels Activated by High-Intensity Focused Ultrasound Liberated β-Glucuronidase.","description":"The poor pharmacokinetics and selectivity of low-molecular-weight anticancer drugs contribute to the relatively low effectiveness of chemotherapy treatments. To improve the pharmacokinetics and selectivity of these treatments, the combination of a doxorubicin-glucuronide prodrug (DOX-propGA3) nanogel formulation and the liberation of endogenous β-glucuronidase from cells exposed to high-intensity focused ultrasound (HIFU) were investigated in vitro. First, a DOX-propGA3-polymer was synthesized. Subsequently, DOX-propGA3-nanogels were formed from this polymer dissolved in water using inverse mini-emulsion photopolymerization. In the presence of bovine β-glucuronidase, the DOX-propGA3 in the nanogels was quantitatively converted into the chemotherapeutic drug doxorubicin. Exposure of cells to HIFU efficiently induced liberation of endogenous β-glucuronidase, which in turn converted the prodrug released from the DOX-propGA3-nanogels into doxorubicin. β-glucuronidase liberated from cells exposed to HIFU increased the cytotoxicity of DOX-propGA3-nanogels to a similar extend as bovine β-glucuronidase, whereas in the absence of either bovine β-glucuronidase or β-glucuronidase liberated from cells exposed to HIFU, the DOX-propGA3-nanogels hardly showed cytotoxicity. Overall, DOX-propGA3-nanogels systems might help to further improve the outcome of HIFU-related anticancer therapy.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jun","modification":"2025-04-19T18:01:40.311Z","creation":"2025-04-19T18:01:40.311Z"},"accession":"S-EPMC7355552","cross_references":{"pubmed":["32532061"],"doi":["10.3390/pharmaceutics12060536"]}}