JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-22
·
IF 10.2
Zhang Shushan,Huang Yongquan,Pi Songying,Chen Hui,Ye Feile,Wu Chaoqun,Li Liujun,Ye Qing,Lin Yuhong,Su Zhongzhen
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.Graphical Abstract
研究领域:
肿瘤学
·
免疫治疗
·
纳米技术
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Weiyu Chen,Yuan Wu,Jianhua Luo,Wei Wei,Qitao Hu,Yiming Xu,Xinjie Zheng,Zhouyi Sun,Lingge Yang,Junkang Ding,Liyun Xu,Shugao Han,Weibo Cai,Kai Wang
Interventional thermal therapy, such as radiofrequency ablation (RFA), is a preferred therapy for non-small cell lung cancer (NSCLC) patients. However, part of some patients will still suffer from tumor recurrence due to incomplete ablation (e.g., restricted thermal conductivity, etc.). Notably, RFA can evoke anti-tumor immunity by releasing tumor-associated antigens (TAAs), but this effect is weak. Herein, to boost thermal and immune therapeutic efficiency for complete tumor eradication, an effective nano-adjuvant (CpG-pIL12-LDHs, LC12), layered double hydroxides (LDHs) carrying immune stimulators, CpG ODN (CpG) and IL-12 plasmid (pIL-12), is developed, which is further integrated into a 3D-printed collar for eliciting potent thermotherapy and therapeutic vaccine against lung cancer. The as-prepared 3D-printed adjuvant collar (3D-LC12) can be attached to the RFA electronic needle and respond to the radiofrequency electrical field during treatment, enhancing ablation temperature, area, and nano-adjuvant's diffusion. After release from the temperature-sensitive collar, LC12 can form an in situ therapeutic cancer vaccine, activate APCs, and remodel the tumor microenvironment (TME), triggering a robust antitumor immune response. Therefore, the current study demonstrates a multi-functional 3D-printed adjuvant collar for efficient eradication of lung cancer via one-time RFA-integrated therapy, providing a novel combined strategy for interventional thermal therapy against tumors.
研究领域:
生物医学工程
·
肿瘤学
·
免疫治疗
·
纳米技术
·
3D打印
·
介入放射学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Meirong Zhang,Shidong Zou,Dingwen Shi,Qingqing Zhang,Mengqin Guo,Xiangliang Yang,Yanbing Zhao
Transcatheter arterial chemoembolization (TACE) exhibits an important role in the treatment of some solid tumors. However, incomplete embolization and angiogenesis-induced tumor relapse and metastasis remain the biggest challenges for TACE. Here, we synthesized metformin-conjugated poly(N-acryloyl glycinamide) ( p Met) nanogels for precisely synergizing TACE with radiofrequency ablation (RFA) to improve antitumor efficacy. p Met nanogels exhibited RF-heating effect and UCST-type gel-sol phase transition, with high performance of sol syringeability, gel strength and thermal stability. Meanwhile, p Met nanogels showed distinct cytotoxicity and suppression of CD24. By the synergistic efficacy with RF-heating, p Met nanogels exhibited significant tumor regression (0.37 ± 0.5) over 36 d in H22-bearing mice. p Met nanogels further down-regulated the levels of PD-1 and Tim-3 of CD8 + T cells and CD25 and CD38 of CD4 + T cells, suggesting their improvement on tumor immunosuppressive microenvironment. The blood-vessel embolization of p Met nanogels was well validated on rabbit ear vessel model. p Met nanogels provide a new paradigm for constructing RF responsive embolic platform.
研究领域:
肿瘤学
·
生物医学工程
·
药学
✓ 已验证
DOI
高影响因子