期刊
BIOMATERIALS
卷 284, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2022.121506
关键词
Hepatocellular carcinoma; NK cell Adoptive therapy; Injectable hydrogel; Tumor acidity; Neutrophil extracellular traps
资金
- National Natural Science Foundation of China [81770651, 81770648, 81972286, 82172585]
- National Key RD Plan [2015A030312013]
- National Key RD Plan [2015A030312013]
- Natural Science Foundation of Guangdong Province [2017B020209004]
- Science and Technology Program of Guangdong Province [20169013, 2020B1212060019, 2020M672984]
- China Postdoctoral Science Foundation [2017ZX10203205]
- National Key Research and Development Program of China [2017YFA0106100]
- [2017YFA0104304]
A dual pH-responsive hydrogel with tumor acidity neutralizer and NETs lyase is developed and used in combination with NK cell infusion to prevent post-resection HCC recurrence, showing promising results in enhancing the efficacy of NK cell therapy.
Post-resection recurrence remains an intractable problem in hepatocellular carcinoma (HCC) management. Natural killer (NK) cell infusion is considered as a promising cancer therapy, but acidic tumor microenvironment (TME) and neutrophil extracellular traps (NETs) greatly counteract its efficacy. Recently, polymer hydrogels have aroused much interest in tumor combination therapy, since they load and controllably release therapeutic agents with high bioavailability and low systemic toxicity. Therefore, a biocompatible hydrogel with tumor acidity neutralizer and NETs lyase may show promise for enhancing NK infusion to prevent post-resection HCC recurrence. Herein, a dual pH-responsive hydrogel with tumor acidity neutralizer (mesoporous bioactive glass nanoparticles) and NETs lyase (Deoxyribonuclease I, DNase I) is developed and used in combination with NK cell infusion for preventing post-resection HCC recurrence. The hydrogel can be injected to surgical margin and form an adhesive gel with a rapid hemostasis. Besides, it neutralizes tumor acidity to reduce tumor infiltration of immunosuppressive cells, and releases DNase I in a pH-responsive manner to degrade NETs. Moreover, this combination therapy significantly enhances NK cell infusion to combat post-surgical HCC recurrence without systemic toxicity. This study provides proof of concept that combination of NK cell adoptive therapy and hydrogel-based delivery system can successfully prevent post-resection HCC recurrence.
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