Multifunctional Hybrid Hydrogel Enhanced Antitumor Therapy through Multiple Destroying DNA Functions by a Triple‐Combination Synergistic Therapy

• Published in: Advanced healthcare materials 2021-11, Vol.10 (21), p.e2101190-n/a
• Main Authors: Zhang, Jiamin, Yang, Lijun, Huang, Fan, Zhao, Cuicui, Liu, Jinjian, Zhang, Yumin, Liu, Jianfeng
• Format: Article
• Language: English
• Subjects: Aggregates; Antitumor activity; Biocompatibility; Brachytherapy; Deoxyribonucleic acid; Destruction; DNA; DNA biosynthesis; DNA damage; DNA repair; Fluorescence; gold nanoparticle aggregates; Hydrogels; Hypoxia; Iodine; Iodine isotopes; Nanoparticles; Radiation damage; Radiation therapy; Radiation tolerance; Radioactive materials; Radioisotopes; Repair; Single photon emission computed tomography; synergistic anti‐tumor therapies; Tumors
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202101190

Brachytherapy, as an effective setting for precise cancer therapy in clinic, can lead to serious DNA damage. However, its therapeutic efficacy is always limited by the DNA self‐repair property, tumor hypoxia‐associated radiation resistance as well as inhomogeneous distribution of the radioactive material. Herein, a multifunctional hybrid hydrogel (131I‐hydrogel/DOX/GNPs aggregates) is developed by loading gold nanoparticle aggregates (GNPs aggregates) and DOX into a radionuclide iodine‐131 (131I) labelled polymeric hydrogels (131I‐PEG‐P(Tyr)8) for tumor destruction by completely damaging DNA self‐repair functions. This hybrid hydrogel exhibits excellent photothermal/radiolabel stability, biocompatibility, and fluorescence/photothermal /SPECT imaging properties. After local injection, the sustained releasing DOX within tumor greatly inhibits the DNA replication. Meanwhile, GNPs aggregates as a radiosensitizer and photosensitizer show a significant improvement of brachytherapeutic efficacy and cause serious DNA damage. Simultaneously, GNPs aggregates induce mild photothermal therapy under 808 nm laser irradiation, which not only inhibits self‐repair of the damaged DNA but also effectively relieves tumor hypoxic condition to enhance the therapeutic effects of brachytherapy, leading to a triple‐synergistic destruction of DNA functions. Therefore, this study provides a highly efficient tumor synergistic therapy platform and insight into the synergistic antitumor mechanism in DNA level. Here, a multifunctional hybrid hydrogel is presented as a DNA destroyer for tumor synergistic therapy. The sustained releasing of DOX in this hydrogel can prevent DNA replication and dual‐sensitizer GNPs aggregates can increase DNA damage and self‐repair inhibition via radiosensitization and mild photothermal therapy. The triple‐synergistic ways can cause multifaceted destruction of DNA functions, achieving a highly efficient antitumor efficacy.