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Abstract:
In this work, we proposed n mu PEF, a novel pulse configuration combining nanosecond and microsecond pulses (n mu PEF), to enhance tumor ablation in irreversible electroporation (IRE) for oncological therapy. n mu PEF demonstrated improved efficacy in inducing immunogenic cell death, positioning it as a potential candidate for next-generation ablative therapy. However, the immune response elicited by n mu PEF alone was insufficient to effectively suppress distant tumors. To address this limitation, we developed PPR@CM-PD1, a genetically engineered nanovesicle. PPR@CM-PD1 employed a polyethylene glycol-polylactic acid-glycolic acid (PEG-PLGA) nanoparticle encapsulating the immune adjuvant imiquimod and coated with a genetically engineered cell membrane expressing programmed cell death protein 1 (PD1). This design allowed PPR@CM-PD1 to target both the innate immune system through toll-like receptor 7 (TLR7) agonism and the adaptive immune system through programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PDL1) checkpoint blockade. In turn, n mu PEF facilitated intratumoral infiltration of PPR@CM-PD1 by modulating the tumor stroma. The combination of n mu PEF and PPR@CM-PD1 generated a potent and systemic antitumor immune response, resulting in remarkable suppression of both n mu PEF-treated and untreated distant tumors (abscopal effects). This interdisciplinary approach presents a promising perspective for oncotherapy and holds great potential for future clinical applications. The study introduces a groundbreaking pulse configuration termed n mu PEF, which synergistically employs nanosecond and microsecond pulses to trigger cancer cell death with an immunogenic pattern. Furthermore, by integrating nanoenabled immunomodulation, n mu PEF amplifies the systemic immune response and curbs the development of secondary tumors, thus presenting a novel outlook for oncological therapy.image
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ADVANCED HEALTHCARE MATERIALS
ISSN: 2192-2640
Year: 2023
Issue: 7
Volume: 13
1 0 . 0
JCR@2023
1 0 . 0 0 0
JCR@2023
JCR Journal Grade:1
CAS Journal Grade:2
Cited Count:
WoS CC Cited Count: 1
SCOPUS Cited Count: 1
ESI Highly Cited Papers on the List: 0 Unfold All
WanFang Cited Count:
Chinese Cited Count:
30 Days PV: 2
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