Necroptosis-Inducible Polymeric Nanobubbles for Enhanced Cancer Sonoimmunotherapy
- Necroptosis-Inducible Polymeric Nanobubbles for Enhanced Cancer Sonoimmunotherapy
- 김광명; 심만규; 곽기정; 양수아; 임승호; 엄우람; 고혜원; 유동길; 이정진; 송애리; 박재형
- Issue Date
- Advanced materials
- VOL 32, NO 16, 1907953
- Necroptosis, caspaseindependent programmed necrosis, has emerged as a therapeutic target to make dying cancer cells stimulants for antitumor immune responses. The clinical translations exploiting necroptosis, however, have been limited since most cancer cells downregulate receptorinteracting protein kinase 3 (RIPK3) as a key enzyme for necroptosis. Herein, nanobubbles (NBs) that can trigger RIPK3independent necroptosis, facilitating cellmembrane rupture via the acoustic cavitation effect are reported. The NBs, imbibing perfluoropentane as the gas precursor, are prepared using an amphiphilic polymer conjugate, composed of PEGylated carboxymethyl dextran as the hydrophilic backbone and chlorin e6 as the hydrophobic sonosensitizer. When exposed to ultrasound, the NBs efficiently promote the release of biologically active damageassociated molecular patterns by inducing burstmediated cellmembrane disintegration. Consequently, the necroptosisinducible NBs significantly improve antitumor immunity by maturation of dendritic cells and activation of CD8+ cytotoxic T cells both in vitro and in vivo. In addition, the combination of NBs and immune checkpoint blockade leads to complete regression of the primary tumor and beneficial therapeutic activity against metastatic tumors in an RIPK3deficient CT26 tumorbearing mouse model. Overall, the innovative NB that causes immunogenic cell death of cancer via RIPK3independent necroptosis is a promising enhancer for cancer immunotherapy.
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