Phase-transition nanodroplets with immunomodulatory capabilities for potentiating mild magnetic hyperthermia to inhibit tumour proliferation and metastasis
作者全名："Qin, Qiaoxi; Zhou, Yang; Li, Pan; Liu, Ying; Deng, Ruxi; Tang, Rui; Wu, Nianhong; Wan, Li; Ye, Ming; Zhou, Hong; Wang, Zhiming"
作者地址："[Qin, Qiaoxi; Zhou, Yang; Liu, Ying; Deng, Ruxi; Ye, Ming; Zhou, Hong] Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Dept Ultrasound, Affiliated Hosp, Chengdu 610031, Peoples R China; [Qin, Qiaoxi; Zhou, Yang; Deng, Ruxi; Wang, Zhiming] Southwest Jiaotong Univ, Inst Biomed Engn, Coll Med, Chengdu 610031, Peoples R China; [Li, Pan; Tang, Rui; Wu, Nianhong] Chongqing Med Univ, Dept Ultrasound, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Li, Pan; Liu, Ying; Tang, Rui; Wu, Nianhong; Wan, Li] Chongqing Med Univ, Inst Ultrasound Imaging, Chongqing 400010, Peoples R China; [Wan, Li] Chongqing Med Univ, Dept Hlth Management Phys Examinat Ctr, Affiliated Hosp 2, Chongqing 400010, Peoples R China"
通信作者："Zhou, Y (通讯作者)，Southwest Jiaotong Univ, Peoples Hosp Chengdu 3, Dept Ultrasound, Affiliated Hosp, Chengdu 610031, Peoples R China.; Zhou, Y (通讯作者)，Southwest Jiaotong Univ, Inst Biomed Engn, Coll Med, Chengdu 610031, Peoples R China."
来源：JOURNAL OF NANOBIOTECHNOLOGY
ESI学科分类：BIOLOGY & BIOCHEMISTRY
关键词：Mild magnetic hyperthermia; Immunogenic cell death; Phase transition; Cavitation effect; Immune adjuvant
摘要："BackgroundMagnetic hyperthermia (MHT)-mediated thermal ablation therapy has promising clinical applications in destroying primary tumours. However, traditional MHT still presents the challenges of damage to normal tissues adjacent to the treatment site and the destruction of tumour-associated antigens due to its high onset temperature (> 50 degrees C). In addition, local thermal ablation of tumours often exhibits limited therapeutic inhibition of tumour metastasis.ResultsTo address the above defects, a hybrid nanosystem (SPIOs + RPPs) was constructed in which phase transition nanodroplets with immunomodulatory capabilities were used to potentiate supermagnetic iron oxide nanoparticle (SPIO)-mediated mild MHT (< 44 degrees C) and further inhibit tumour proliferation and metastasis. Magnetic-thermal sensitive phase-transition nanodroplets (RPPs) were fabricated from the immune adjuvant resiquimod (R848) and the phase transition agent perfluoropentane (PFP) encapsulated in a PLGA shell. Because of the cavitation effect of microbubbles produced by RPPs, the temperature threshold of MHT could be lowered from 50celcius to approximately 44celcius with a comparable effect, enhancing the release and exposure of damage-associated molecular patterns (DAMPs). The exposure of calreticulin (CRT) on the cell membrane increased by 72.39%, and the released high-mobility group B1 (HMGB1) increased by 45.84% in vivo. Moreover, the maturation rate of dendritic cells (DCs) increased from 4.17 to 61.33%, and the infiltration of cytotoxic T lymphocytes (CTLs) increased from 10.44 to 35.68%. Under the dual action of mild MHT and immune stimulation, contralateral and lung metastasis could be significantly inhibited after treatment with the hybrid nanosystem.ConclusionOur work provides a novel strategy for enhanced mild magnetic hyperthermia immunotherapy and ultrasound imaging with great clinical translation potential."