ACS Nano
·
2021
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IF 15.881
Zhongyuan Chen,Yueting Peng,Yichao Li,Xiaoxue Xie,Xiaodan Wei,Geng Yang,Hanxi Zhang,Ningxi Li,Tingting Li,Xiang Qin,Shun Li,Chunhui Wu,Fengming You,Hong Yang,Yiyao Liu
The combination of magnetic hyperthermia and chemotherapy within a nanosystem is thought to be a promising approach for cancer therapies. However, the nonspecific accumulation and fast clearance of magnetic nanoparticles in the physiological environment limited their further biomedical applications. Herein, we report a highly selective theranostic nanocomplex, ZIPP-Apt:DOX/siHSPs, built with superparamagnetic zinc-doped iron oxide nano-octahedral core, cationic PAMAM dendrimer, and functional surface modifications such as PEG, AS1411 aptamer, and fluorescent tags (FITC or Cy5.5), together with the loading of hydrophobic anticancer drug doxorubicin (DOX) and HSP70/HSP90 siRNAs. Our results demonstrate that the cellular uptake and the tumor-specific accumulation of ZIPP-Apt:DOX/siHSPs were significantly increased due to the AS1411-nucleolin affinity and further confirmed that the simultaneous depletion of HSP70 and HSP90 sensitized magnetic hyperthermia and chemotherapy-induced cell death both in vitro and in vivo. Altogether, our study provides a theranostic nanoplatform for aptamer-targeted, NIR/MR dual-modality imaging guided, and HSP70/HSP90 silencing sensitized magnetochemotherapy, which has the potential to advance versatile magnetic nanosystems toward clinical applications.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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分子生物学
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药学
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医学影像
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2022
·Vol. 9
·期 29
·2201541
·
IF 17.521
Jiawei Huo,Jie Li,Yang Liu,Libin Yang,Xinran Cao,Chong Zhao,Yicheng Lu,Wei Zhou,Shumu Li,Jianan Liu,Jiao Li,Xing Li,Jing Wan,Rui Wen,Mingming Zhen,Chunru Wang,Chunli Bai
Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi-targeted cancer drugs. It is an urgent need to reveal the structure–activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC-4, TAPC-3, and TCPC-4. TAPC-4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial–mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC-4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC-4 to heat shock protein Hsp90-beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti-tumor drug development.
研究领域:
肿瘤学
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药物化学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Nano Today
·
2023
·
IF 17.4
Honglei Zhu,Huayan Li,Kunjie Gao,Yi Huang,Yuru Liao,Weichu Hu,Feng Chen,Haoyuan Jiang,Xiaomei Liang,Haonan Song,Yuxin Wang,Hanrong Huang,Yifan Wang,Fan Liu,Hao Huang,Qian Wang,Xiao Yi
Intrauterine adhesion (IUA) is one of the main causes of female infertility. Extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs), are consisted of a complete lipid bilayer structure, rich in multiple factors and miRNAs related to tissue regeneration , which are the main effective paracrine components of MSCs to treat IUA. However, the poor secretion and bioactivity of EVs leading to the unexpected therapeutic efficacy of MSC-EVs, have been obstacles to their widespread use in clinical practice. Here, we developed human chorionic villi (CV)-derived nanofibers that mimic the tissue-specific ECM microenvironment of CV-derived MSCs, maintain the stemness of MSCs for a long time, and are rich in apolipoproteins , HSP90 , ANXA1-A6, etc., which can enhance EV secretion and bioactivity. Then, the CV-nanofiber bionic culture system for mesenchymal stem cells was constructed to achieve large-scale cultivation of MSCs for continuous collection of high-concentration EVs enrichment supernatant. Additionally, EVs obtained by this system were encapsulated with CV-nanofibers to form EVs-ECM aggregate, which can effectively promote endometrium regeneration toward supporting fetal development and live births. Our study provides a new idea for enhancing EV secretion and bioactivity, and a cell-free therapy for treating IUA by EVs, thus promoting the potential of clinical application.
研究领域:
生殖医学
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干细胞生物学
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组织工程
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再生医学
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Jie Sheng,Ziyue Zu,Jianchen Qi,Yugang Zhang,Haoguang Wu,Zhicheng Wang,Yu Miao,Tao Zheng,Sheng Wang,Linlin Zhang,Guangming Lu,Longjiang Zhang
Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.
研究领域:
心血管疾病
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纳米技术
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治疗策略
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炎症
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脂质代谢
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2024
·
IF 4.5
Jinmei Lai,Qunying Shi,Yongqi Xie,Yinyin Zhu,Shiyu Liang,Yi Chen,Jiali Yuan,Lihan Liu
Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE–PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.
研究领域:
纳米技术
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肿瘤学
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治疗诊断学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Jia Liu,Liuting Zheng,Xinyue Li,Wei Tang,Manyu Guo,Yuxing Wang,Xiaoqi Tan,Jiajia Chang,Huiyue Zhao,Dongsheng Zhu,Yu-qiang Ma,Da Huo
Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions. Uptake of AuNRs causes reactive oxygen species accumulation and protein misfolding in the cell, leading to NSG formation. Physically, NSGs have a gel-like core and a liquid-like shell, influenced positively by HSP70 and negatively by HSP90 and the ubiquitin-proteasome system. AuNRs promote NSG assembly by interacting with G3BP1, reducing the energy needed for liquid–liquid phase separation (LLPS). NSGs impact cellular functions by affecting mRNA surveillance and activating Adenosine 5′-monophosphate (AMP)-activated protein kinase signaling, crucial for a cellular stress response. Our study highlights the role of LLPS in nanomaterial metabolism and suggests NSGs as potential targets for drug delivery strategies, advancing the field of nanomedicine.
研究领域:
纳米生物技术
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细胞生物学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Weijuan Zou,Longchen Wang,Junnian Hao,Lixian Jiang,Wenxian Du,Tao Ying,Xiaojun Cai,Haitao Ran,Jianrong Wu,Yuanyi Zheng
Insufficient concentrations of intracellular substrates such as hypoxia and H 2 O 2 considerably reduce the effectiveness of reactive oxygen species (ROS)-associated cancer therapy. Modulating the tumor microenvironment (TME) for augmenting efficacy has become a promising strategy. Herein, a phase-change cascaded nanomedicine (Lap-IrO x @PCM) was constructed via co-encapsulation of iridium oxide nanozyme (IrO x ) and β-lapachone (Lap) by using thermal-responsive phase-change materials (PCMs). After photothermal activation, the protective PCM layer was melted, causing the rapid release of IrO x and Lap. Simultaneously, the peroxidase-like nanozyme IrO x reacted with endogenous H 2 O 2 to liberate highly toxic hydroxyl radicals (•OH) for inducing tumor cell death. Meanwhile, IrO x as another glutathione peroxidase nanozyme also consumed glutathione (GSH) to protect ROS from scavenging. Importantly, the released Lap efficiently generated H 2 O 2 for facilitating the catalytic efficacy of IrO x and provoke the cleavage of heat shock protein 90 (Hsp90) for overcoming tumor heat tolerance in photothermal therapy (PTT). As systematically demonstrated both in vitro and in vivo , this well-defined system achieved a superior antitumor effect via mild photothermal-enhanced nanocatalytic therapy. Our findings have provided the proof of concept of the phase change-mediated, in vivo catalytic activity of nanozymes that can be customized for intensive, TME-mediated, self-enhanced nanocatalytic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 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）