Highly Tumor-Specific and Long-Acting Iodine-131 Microbeads for Enhanced Treatment of Hepatocellular Carcinoma with Low-Dose Radio-Chemoembolization
| Autor: | Jiaojiao Xu, Jingwen Sun, Wei Lu, Qiufang Liu, Panli Li, Aihua Wu, Yuyi Qian, Shaoli Song, Yaobao Han, Jianping Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
Carcinoma
Hepatocellular Tare weight General Physics and Astronomy 02 engineering and technology 010402 general chemistry 01 natural sciences Ionizing radiation Iodine Radioisotopes medicine Distribution (pharmacology) Animals General Materials Science Doxorubicin Chemoembolization Therapeutic Chemistry Therapeutic effect Liver Neoplasms General Engineering 021001 nanoscience & nanotechnology medicine.disease Microspheres 0104 chemical sciences Rats Hepatocellular carcinoma Cancer research Lipiodol Doxorubicin Hydrochloride 0210 nano-technology medicine.drug |
| Zdroj: | ACS nano. 15(2) |
| ISSN: | 1936-086X |
| Popis: | Transarterial radioembolization (TARE) is considered the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Iodine-131 (131I)-labeled lipiodol TARE is an effective treatment for HCC but has been withdrawn due to its poor retention in tumor lesions and significant distribution in normal tissues with severe side effects. In this work, a highly tumor-specific 131I-TARE agent with long-time retention is developed by simply introducing tyrosine to poly(vinyl alcohol) (PVA) drug-eluting microbeads (Tyr-PVA-DEBs). The labeling efficiency of 131I-labeled microbeads remains above 85% in 50% serum for 31 days. Micro-single-photon emission computed tomography/computed tomography (μSPECT/CT) evidences that the 131I-labeled microbeads accumulate in the orthotopic N1S1 hepatoma of rats for 31 days following intra-arterial injection. The cumulative radiation dose per cubic centimeter of the tumor is at least 13 678-fold higher than that of normal tissues. The highly tumor-selective radiation of the 131I-labeled microbeads allows localized delivery of 345.04 ± 139.16 Gy to the tumor following a single injection dose as low as 0.2 mCi of 131I. Moreover, the 131I-labeled microbeads are loaded with doxorubicin hydrochloride (DOX) through the carboxy groups on tyrosine of the polymer. The 131I-DOX-loaded microbeads present a synergetic antitumor effect without recurrence in comparison with the microbeads labeled with 131I or loading DOX alone, attributed to the sensitization of DOX to 131I-induced ionizing radiation damage to DNA under the embolization-induced hypoxia. Our results demonstrate a high tumor retention of 131I-labeled embolic agent for low-dose transarterial radio-chemoembolization (TARCE) with a synergetic therapeutic effect on treating HCC, showing potential for clinical application. |
| Databáze: | OpenAIRE |
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