Necroptosis‐Inducible Polymeric Nanobubbles for Enhanced Cancer Sonoimmunotherapy. Issue 16 (3rd March 2020)

• Record Type: Journal Article
• Authors: Um, Wooram; Ko, Hyewon; You, Dong Gil; Lim, Seungho; Kwak, Gijung; Shim, Man Kyu; Yang, Suah; Lee, Jeongjin; Song, Yeari; Kim, Kwangmeyung; Park, Jae Hyung
• Is Part Of: Advanced materials. Volume 32:Issue 16(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-03-03
• Subjects: damage‐associated molecular patterns -- immune checkpoint blockade -- necroptosis -- reactive oxygen species -- sonodynamic therapy; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.201907953
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: Necroptosis, caspase‐independent 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 receptor‐interacting protein kinase 3 (RIPK3) as a key enzyme for necroptosis. Herein, nanobubbles (NBs) that can trigger RIPK3‐independent necroptosis, facilitating cell‐membrane 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 damage‐associated molecular patterns by inducing burst‐mediated cell‐membrane disintegration. Consequently, the necroptosis‐inducible 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 RIPK3‐deficient CT26 tumor‐bearing mouse model. Overall, the innovative NB that causes immunogenic cell death of cancer via RIPK3‐independent necroptosis is a promising enhancer for cancer immunotherapy. Abstract : Necroptosis‐inducible nanobubbles (NBs) facilitate cell‐membrane rupture via the acoustic cavitation effect, leading to RIPK3‐independent necroptosis. These may elicit the enhanced immunogenicity of dying cells and damage‐associated molecular patterns, compared to apoptosis inducers. Under ultrasound irradiation, NBs significantly improve the therapeutic response of immune checkpoint blockade therapy and demonstrate beneficial antitumor efficacy against metastatic tumors.