ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jia Liu,Lei Zhao,Lin Shi,Ye Yuan,Daan Fu,Zhilan Ye,Qilin Li,Yan Deng,Xingxin Liu,Qiying Lv,Yanni Cheng,Yunruo Xu,Xulin Jiang,Guobin Wang,Lin Wang,Zheng Wang
Cancer chemotherapy is challenged by multidrug resistance (MDR) mainly attributed to overexpressed transmembrane efflux pump P-glycoprotein (P-gp) in cancer cells. Improving drug delivery efficacy while co-delivering P-gp inhibitors to suppress drug efflux is an often-used nanostrategy for combating MDR, which is however challenged by cascaded bio-barriers en route to cancer cells and P-gp inhibitors’ adverse effects. To effectively breach the cascaded bio-barriers while avoiding P-gp inhibitors’ adverse effects, a stealthy, sequentially responsive doxorubicin (DOX) delivery nanosystem (RCMSNs) is fabricated, composed of an extracellular-tumor-acidity-responsive polymer shell (PEG-b-PLLDA), pH/redox dual-responsive mesoporous silica nanoparticle-based carriers (MSNs-SS-Py), and cationic β-cyclodextrin-PEI (CD-PEI) gatekeepers. The PEG-b-PLLDA corona makes RCMSNs stealthy with prolonged blood circulation time. Once tumors are reached, extracellular acidity degrades PEG-b-PLLDA, reversing nanosystem’s surface charges to be positive, which drastically improves RCMSNs’ tumor accumulation, penetration, and cellular internalization. Within cancer cells, CD-PEI gatekeepers detach to allow DOX unloading in response to intracellular acidity and glutathione and functionally act as a P-gp inhibitor, dampening P-gp’s efflux activity by impairing ATP production. Thus, the resultant high-efficacy drug delivery along with reduced P-gp function cooperatively reverses MDR in vitro. Importantly, in preclinical tumor models, DOX@RCMSNs potently suppress MDR tumor growth without eliciting systemic toxicity, demonstrating their potential of clinical translation.
研究领域:
纳米技术
·
药学
·
肿瘤学
·
生物医学工程
·
药物递送系统
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 15
·期 9
·8326-8335
·
IF 10.269
Li Xiangxia,Chen Guiyuan,Wang Yangyi,Su Lanhong,Chen Bo,Wu Kecheng,Xing Yun,Song Zechenxi,Dai Ruike,Liu Tianxin,Zhao Jiaao,Xie Zhe,Zhou Peijie,Xia Xiaoping,Min Yuanzeng
In the tumor immunosuppressive microenvironment (TIME), antigen presenting cells (APCs) usually exhibit a tumor suppressor phenotype. Toll-like receptors (TLRs) agonists could reprogram M2-type macrophages to M1-type and stimulate dendritic cells (DCs) maturation. The combination of TLR7/8 and TLR9 agonists seems to have synergistic therapeutic efficacy. Here, we designed a lipid-coated mesoporous silica nanoparticle (MSNs@Lipo) for the co-delivery of TLR7/8 agonist resiquimod (R848) and TLR9 agonist CpG oligodeoxynucleotides (ODNs) (CpG@MSNs-R@L-M). R848 was firstly conjugated onto the nanoparticle via silane chemistry, which is acidic responsive drug release. Then, CpG was loaded onto the nanoparticle through the positive charge mainly from TLR7/8 agonist R848. Our in vitro experiments further indicated that both drugs have acid-responsive release properties and could be taken up by DCs and located on the endosomes of APCs. More importantly, CpG@MSNs-R@L-M could significantly improve the antitumor efficacy in B16F10 melanoma model. The mechanistic study demonstrated that CpG@MSNs-R@L-M could remarkably modulate the TIME by promoting the maturation of DCs and repolarizing macrophages from M2 to M1 phenotype and facilitating the infiltration of tumor cytotoxic T cells. It was concluded that in comparison to single agonist, the co-delivery of dual agonists, CpG and R848, can improve anti-tumor immune responses for cancer immunotherapy.
研究领域:
免疫学
·
纳米医学
·
肿瘤学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2019
·
IF 8.355
Yingying Zhang,Hongbin Chen,Hanjie Wang,Tiange Wang,Huizhuo Pan,Wanying Ji,Jin Chang
Immunotherapy has become a promising therapy in cancer treatment. Both photothermal therapy (PTT) and genotoxic chemotherapy can trigger immune responses. On this subject, a synergistic cancer immunotherapy nano-system was developed for treating primary and distant tumors. This long-time, synergistic therapeutic system consisted of two parts: one was indocyanine green (ICG) and sepantronium bromide (YM155) co-loaded mesoporous silica nanoparticles (MSNs) for PTT and genotoxic chemotherapy, which could effectively destroy primary tumors and thus cause exposure of tumor antigens for cancer immunotherapy. The other was silica nanoparticles (nSiO 2 ) coated with magnetic nanoparticles (MNP) and conjugated with anti-CD47 antibody (anti-CD47), which demonstrated a strong antitumor immune effect of distant tumors after PTT and genotoxic chemotherapy. In vitro and vivo results proved that this synergistic system could efficiently inhibit primary and distant tumor growth. We expected that this paper may develop a promising strategy to prevent tumor growth for basic and clinical research.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）