Nano Today最新文献_第5页

Tracing the graphitization of polymers: A novel approach for direct atomic-scale visualization 追踪聚合物的石墨化：原子尺度直接可视化的新方法

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-23 DOI: 10.1016/j.nantod.2024.102524

Chloé Chemin, Babak Rezaei, Ada-Ioana Bunea, Stephan Sylvest Keller, Alice Bastos da Silva Fanta, Thomas Willum Hansen

{"title":"Tracing the graphitization of polymers: A novel approach for direct atomic-scale visualization","authors":"Chloé Chemin, Babak Rezaei, Ada-Ioana Bunea, Stephan Sylvest Keller, Alice Bastos da Silva Fanta, Thomas Willum Hansen","doi":"10.1016/j.nantod.2024.102524","DOIUrl":"10.1016/j.nantod.2024.102524","url":null,"abstract":"<div><div>Due to its excellent physical, chemical, and electrochemical characteristics, pyrolytic carbon has become a promising material for a wide range of advanced technologies. Pyrolytic carbon can be obtained through the pyrolysis of a polymeric carbon precursor at high temperatures and in inert atmosphere. By tuning the pyrolysis conditions, the hybridization of carbon atoms and thus the physicochemical properties of the derived carbon can be tailored. Advancing its development requires a deeper understanding of the graphitization process. In this context, an <em>in situ</em> microstructural analysis of the pyrolysis process is needed. This work presents the microfabrication of suspended polymer thin film structures on transmission electron microscopy heating chips, by two-photon polymerization 3D printing. We visualized graphitization of these films during <em>in situ</em> transmission electron microscopy heating studies. The favorable identified conditions are a thin film with a thickness of around 700 nm pre-pyrolysis, a pyrolysis profile reaching a maximum temperature of 1300°C and a minimum of 2 h of dwell at this temperature. An increase in the number of stacked graphene layers was observed over dwell time. Overall, the developed method has the potential to enable the visualization of graphitization of different polymer precursors and thus help predict the microstructure and properties of pyrolytic carbon depending on its fabrication conditions.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102524"},"PeriodicalIF":13.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic and responsive release mechanisms of polymer drug conjugates with diverse polymer skeletons 具有不同聚合物骨架的聚合物药物共轭物的治疗和响应释放机制

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-22 DOI: 10.1016/j.nantod.2024.102526

Wenjie Zhao, Kaichuang Sun, Jianqin Yan, Yong Sun, Dengshuai Wei

{"title":"Therapeutic and responsive release mechanisms of polymer drug conjugates with diverse polymer skeletons","authors":"Wenjie Zhao, Kaichuang Sun, Jianqin Yan, Yong Sun, Dengshuai Wei","doi":"10.1016/j.nantod.2024.102526","DOIUrl":"10.1016/j.nantod.2024.102526","url":null,"abstract":"<div><div>Polymer-drug conjugates (PDCs) have emerged as an advanced strategy in the drug delivery. The conjugation of therapeutic or diagnostic agents to polymers, such as polyurethane, polyester, RAFT-based polymers, and poly(amino acid)s, presents several advantages, including enhanced drug solubilization, controlled release, reduced immunogenicity, prolonged circulation, improved safety, and increased efficacy. Recent research has focused extensively on engineering efficient tumor microenvironment (TME)-responsive PDCs, leading to significant advancements in cancer diagnosis and therapy. This review discusses the rational design, mechanisms of responsive release, physicochemical properties, and recent developments in various polymer systems for PDCs. We categorize PDCs based on their skeletal designs, including polyurethane, polyester, RAFT polymers, and polyamino acids. Additionally, we emphasize the TME responsiveness of PDCs, highlighting its critical role in various tumor therapies. Finally, we address the current challenges faced by PDCs and offer perspectives for future research, providing insights into the utility and potential of this technology. We hope this review serves as a valuable resource for the selection and optimization of PDCs, facilitating their future applications in cancer therapeutics.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102526"},"PeriodicalIF":13.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-fidelity CRISPR/Cas13a trans cleavage-driven assembly of single quantum dot nanosensor for ultrasensitive detection of long noncoding RNAs in clinical breast tissues 高保真 CRISPR/Cas13a 反式裂解驱动的单量子点纳米传感器组装，用于超灵敏检测临床乳腺组织中的长非编码 RNA

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-21 DOI: 10.1016/j.nantod.2024.102529

Wen-jing Liu , Hai-juan Li , Jinqiu Tao , Lu-yao Wang , Juan Hu , Chun-yang Zhang

{"title":"High-fidelity CRISPR/Cas13a trans cleavage-driven assembly of single quantum dot nanosensor for ultrasensitive detection of long noncoding RNAs in clinical breast tissues","authors":"Wen-jing Liu , Hai-juan Li , Jinqiu Tao , Lu-yao Wang , Juan Hu , Chun-yang Zhang","doi":"10.1016/j.nantod.2024.102529","DOIUrl":"10.1016/j.nantod.2024.102529","url":null,"abstract":"<div><div>Long noncoding RNAs (lncRNAs) act as critical regulators in various cellular processes, and their dysfunction is implicated in carcinogenesis. Herein, we demonstrate high-fidelity CRISPR/Cas13a <em>trans</em> cleavage-driven assembly of single quantum dot (QD) nanosensor for ultrasensitive detection of long noncoding RNAs in clinical tissues. The presence of lncRNA can activate Cas13a/crRNA to collaterally cleave the substrate probes, producing a T7 promoter fragment that can initiate subsequent transcription amplification to generate efficient fluorescence resonance energy transfer (FRET). Taking advantage of excellent specificity of high-fidelity CRISPR/Cas13a system, high efficiency of transcription amplification, and near-zero background of single QD-based FRET, this nanosensor can achieve a detection limit of 1.65 aM, and it can differentiate target lncRNA from its mismatched members with single-base resolution. Moreover, it can measure lncRNA at the single-cell level, distinguish diﬀerent subtypes of breast cancers, and assess the breast cancer progression. Notably, due to the programmability of crRNAs, this nanosensor can be extended to detect other nucleic acids (e.g., SARS-CoV-2 RNA, circRNA, miRNA, piRNA, and 16S rRNA) by simply altering the spacer region of crRNA, with great potential in lncRNAs-related molecular diagnostics.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102529"},"PeriodicalIF":13.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dual-lock-and-key virus-mimicking nanoprobes for ultra-high accurate and sensitive imaging of viral infections in vivo 用于对体内病毒感染进行超高精度和灵敏度成像的双锁键病毒模拟纳米探针

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-20 DOI: 10.1016/j.nantod.2024.102527

Cong Yu , Hua-Jie Chen , Hao-Yang Liu , Di Ning , Lei Wang , Xue-Hui Shi , Zhi-Gang Wang , Dai-Wen Pang , Shu-Lin Liu

{"title":"Dual-lock-and-key virus-mimicking nanoprobes for ultra-high accurate and sensitive imaging of viral infections in vivo","authors":"Cong Yu , Hua-Jie Chen , Hao-Yang Liu , Di Ning , Lei Wang , Xue-Hui Shi , Zhi-Gang Wang , Dai-Wen Pang , Shu-Lin Liu","doi":"10.1016/j.nantod.2024.102527","DOIUrl":"10.1016/j.nantod.2024.102527","url":null,"abstract":"<div><div>Fluorescence in situ imaging of viral infection lesions in vivo is crucial for precise diagnosis of viral diseases and evaluation of the extent of viral infection. Nevertheless, achieving highly specific and sensitive fluorescence imaging of viral infection sites in vivo has posed a persistent challenge. Here, we developed a dual-lock-and-key virus-mimicking nanoprobe that consisted of polyamide dendrimers (PAMAM) loaded internally with molecular beacons double-triggered by apurinic/apyrimidinic nucleic acid endonuclease 1 (APE1) and viral RNA (vRNA), and surface-modified with the E protein of Japanese encephalitis virus (JEV). This activatable nanoprobe generated dramatically amplified fluorescent signals stimulated by expressed vRNA and APE1 during viral infection, enabling ultrahigh specific and sensitive imaging of the lesions of JEV infection in vivo. This study provides a potential approach for accurate and sensitive detection of viral infection levels and assessment of the efficacy of antiviral drugs in vivo.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102527"},"PeriodicalIF":13.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142540092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atomic-scale probing of ion migration dynamics in Na3Ni2SbO6 cathode for sodium ion batteries 用于钠离子电池的 Na3Ni2SbO6 阴极中离子迁移动力学的原子尺度探测

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-17 DOI: 10.1016/j.nantod.2024.102523

Ke Qu , Jianwei Zhang , Haonan Wang , Fan Wu , Huahui Lin , Jianchu Chen , Zhengping Ding , Zhenzhong Yang , Peng Gao

{"title":"Atomic-scale probing of ion migration dynamics in Na3Ni2SbO6 cathode for sodium ion batteries","authors":"Ke Qu , Jianwei Zhang , Haonan Wang , Fan Wu , Huahui Lin , Jianchu Chen , Zhengping Ding , Zhenzhong Yang , Peng Gao","doi":"10.1016/j.nantod.2024.102523","DOIUrl":"10.1016/j.nantod.2024.102523","url":null,"abstract":"<div><div>Honeycomb-layered phases like Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> have been extensively researched as high-voltage and high-rate capability cathode materials for sodium-ion batteries. However, our understanding of the structural stability and dynamic reaction mechanisms of Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> cathode during cycling, especially at atomic-scale, remains limited. Here, we track the microstructure evolution during extraction of Na<sup>+</sup> ions in Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> cathode at atomic scale in an aberration-corrected transmission electron microscope. The electron beam irradiation that can provide a driving force for the Na<sup>+</sup> ion migration, allows us to mimic the battery charge process. By controlling the electron beam dose, we study the structure evolution behavior to obtain insights into understanding the work principle and failure mechanism of Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> cathode under different charge rate conditions. We find that the real-time structural evolution and ion migration pathways of Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> cathode are distinct under different electron beam doses. High-dose irradiation reveals Na ion depletion, surface cracks, and phase transformations, mimicking rapid capacity decay. In contrast, low-dose irradiation shows slower ion migration, ordered Na vacancy formation, and maintaining structural integrity, which more closely resembles the electrochemical process of actual battery. This study provides an atomistic understanding of the structural stability and Na ions deintercalation mechanism in Na<sub>3</sub>Ni<sub>2</sub>SbO<sub>6</sub> cathodes, offering new insights into optimizing electrode materials.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102523"},"PeriodicalIF":13.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Three-dimensional magnetophoretic bioassay based on artificial intelligence-mediated load assignment for the femtomolar and washing-free detection of analytes 基于人工智能负载分配的三维磁泳生物分析法，用于飞摩尔和免清洗分析物检测

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-16 DOI: 10.1016/j.nantod.2024.102522

Ting Xiao , Weiqi Zhao , Minjie Han , Xiaolin Huang , Ben Zhong Tang , Yiping Chen

{"title":"Three-dimensional magnetophoretic bioassay based on artificial intelligence-mediated load assignment for the femtomolar and washing-free detection of analytes","authors":"Ting Xiao , Weiqi Zhao , Minjie Han , Xiaolin Huang , Ben Zhong Tang , Yiping Chen","doi":"10.1016/j.nantod.2024.102522","DOIUrl":"10.1016/j.nantod.2024.102522","url":null,"abstract":"<div><div>The quantification of low-abundance biomarkers or trace harmful substances in complex samples at femtomolar-level sensitivity requires labor-intensive incubation and multiwashing steps. Herein, we explore a trajectory/accumulation/color three-dimensional microfluidic magnetophoresis immunoassay (TAC-MMI) based on an artificial intelligence (AI)-assisted load assignment strategy, enabling washing-free and femtomolar detection of interleukin-6 in serum samples and chloramphenicol in food samples within 30 min. The biorecognition between targets and biometric molecules (antigens and antibodies) immobilized on magnetic nanoparticles (MNPs) and polystyrene microsphere-horseradish peroxidase (PM-HRP) conjugate induces MNP-target-PM-HRP immunocomplexes with different magnetic contents, where the concentration of targets is transformed into spatial visualization information through magnetophoretic force using a linear microtube array within a microfluidic chip. The visualization information can be enhanced by the HRP-catalyzed color reaction. Trajectory-accumulation-color of PM in each microtube is precisely assigned significance and identified via AI for bioanalysis. TAC-MMI demonstrates high sensitivity (fM level), rapidity (30 min), and ease of use without washing steps. The three-dimensional sensing strategy based on load-assignment improved sensitivity by more than 96-fold compared with the traditional one-dimensional sensing strategy. Compared to chemiluminescence immunoassay (CLIA), TAC-MMI achieved 15-fold improvement in sensitivity in only one-third of the time required for CLIA, suggesting a promising magnetophoretic bioassay for diagnostic technology.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102522"},"PeriodicalIF":13.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vivo engineering chimeric antigen receptor immune cells with emerging nanotechnologies 利用新兴纳米技术在体内制造嵌合抗原受体免疫细胞

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-10 DOI: 10.1016/j.nantod.2024.102517

Hui Ren , Yuzhi Jin , Huanhuan Huang , Wei Wu , Xiaomeng Dai , Weijia Fang , Jing Qin , Hongjun Li , Peng Zhao

{"title":"In vivo engineering chimeric antigen receptor immune cells with emerging nanotechnologies","authors":"Hui Ren , Yuzhi Jin , Huanhuan Huang , Wei Wu , Xiaomeng Dai , Weijia Fang , Jing Qin , Hongjun Li , Peng Zhao","doi":"10.1016/j.nantod.2024.102517","DOIUrl":"10.1016/j.nantod.2024.102517","url":null,"abstract":"<div><div>Adoptive cell therapy with chimeric antigen receptor (CAR) has revolutionized cancer treatment in the past decade. Now several adoptive cell therapies are approved, and researchers are extending the application of adoptive cell therapy beyond oncology, such as autoimmune diseases, inherited blood disorders, infectious diseases and fibrosis. Evidence from clinical studies underscores the potential of cell therapy in cancer and noncancerous conditions. However, conventional manufacture of adoptive CAR-cell <em>ex vivo</em> is time-consuming and expensive in which immune cells are extracted from the patients, engineered to target cancer cells and reinjected to the body. The ways to produce CAR-cell in the body, as a promising alternative, may make the awfully expensive and personalized cell therapy more accessible. Here, we thoroughly summarize the current state of clinical trials on adoptive cell therapy, representing by CAR-T, CAR-nature killer cell (CAR-NK) and CAR-Macrophage (CAR-M), and highlight the latest advances in off-the-shelf nanocarrier- and virus-based <em>in vivo</em> CAR cargo delivery strategies, and corresponding precision targeting strategies, to provide a future perspective regarding <em>in vivo</em> engineering CAR-cell.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102517"},"PeriodicalIF":13.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomimetic nanoreactor of catalase and nitric oxide enhance peroxynitrite generation for radiosensitization 过氧化氢酶和一氧化氮的仿生纳米反应器可增强过氧化亚硝酸盐的生成，从而提高辐射敏感性

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-07 DOI: 10.1016/j.nantod.2024.102519

Yao Wu , Yongping Li , Honglei Xie , Yichen Zhang , Xinyue Bao , Xianyi Sha , Jingyuan Wen , Yaping Li , Zhiwen Zhang

{"title":"Biomimetic nanoreactor of catalase and nitric oxide enhance peroxynitrite generation for radiosensitization","authors":"Yao Wu , Yongping Li , Honglei Xie , Yichen Zhang , Xinyue Bao , Xianyi Sha , Jingyuan Wen , Yaping Li , Zhiwen Zhang","doi":"10.1016/j.nantod.2024.102519","DOIUrl":"10.1016/j.nantod.2024.102519","url":null,"abstract":"<div><div>The redundant DNA-repairing capacity and robust hypoxia in tumors pose significant challenges of cancer radiotherapy. Herein, an amphiphilic nitric oxide (NO)-supplying conjugate (PEG−SMA−NO) was synthesized and integrated with oxygen-producing catalase (CAT) to fabricate a biomimetic nanoreactor (termed as CAT@PNN), aiming to enhance peroxynitrite generation upon X-ray radiation for radiosensitization. CAT@PNN effectively reduced the hypoxic levels and produced abundant NO molecules in tumors. Upon X-ray radiation, excessive peroxynitrite radicals were generated with profound spatiotemporal distribution profiles, which effectively downregulated the expression of DNA-repairing RAD51, reduced the proportion of cancer-stem like cells, and enhanced the levels of DNA damages, cell apoptosis and lipid peroxidation to aid radiosensitization. Specifically, the combination of single treatment of CAT@PNN with X-ray radiation resulted in a 95.41 % inhibition of tumor growth and significantly extended survival in 4T1 tumor model. Therefore, the biomimetic nanoreactor of CAT@PNN offers a promising peroxynitrite-generating nanoplatform to enhance radiosensitization in cancer radiotherapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102519"},"PeriodicalIF":13.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liquid-liquid phase separation in human diseases: Functions, mechanisms and treatments 人类疾病中的液-液相分离：功能、机制和治疗

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-07 DOI: 10.1016/j.nantod.2024.102521

Tongqing Yue , Fei Zhang , Yanan Wei, Zejun Wang

引用次数: 0

MCL1 inhibitor S63845 delivered by follicle-stimulating hormone modified liposome potentiates carboplatin efficacy in ovarian cancer 通过卵泡刺激素修饰脂质体递送的 MCL1 抑制剂 S63845 可增强卡铂对卵巢癌的疗效

IF 13.2 1区材料科学

Nano Today Pub Date : 2024-10-05 DOI: 10.1016/j.nantod.2024.102513

Yanan Zhang , Qingzhen Wang , Wenxin Li , Xin Li , Yuqing Li , Zhihua Liu , Huige Zhou , Aiping Luo , Chunying Chen , Bin Li

{"title":"MCL1 inhibitor S63845 delivered by follicle-stimulating hormone modified liposome potentiates carboplatin efficacy in ovarian cancer","authors":"Yanan Zhang , Qingzhen Wang , Wenxin Li , Xin Li , Yuqing Li , Zhihua Liu , Huige Zhou , Aiping Luo , Chunying Chen , Bin Li","doi":"10.1016/j.nantod.2024.102513","DOIUrl":"10.1016/j.nantod.2024.102513","url":null,"abstract":"<div><div>Platinum resistance cause therapeutic failure and poor prognosis in ovarian cancer, and evasion of apoptosis is a critical factor in chemoresistance. A limited number of FDA-approved anticancer drugs directly target apoptotic pathways. Here, we discovered that MCL1, a critical anti-apoptotic protein, is amplified and associated with platinum resistance and survival in ovarian cancer, assisting in personalized treatment. We further identified S63845 through drug-based screening, the most potent MCL1 inhibitor, which efficiently enhanced carboplatin (CBP) sensitivity in various ovarian cancer models, including primary ovarian cancer cells, orthotopic ovarian cancer, peritoneal metastasis, and human patient-derived xenograft (PDX) models. Mechanistically, S63845 competitively binds to MCL1, disrupts the binding of apoptosis effector (BAK and BAX) or pro-apoptotic BH3 protein (BIM) to MCL1 respectively, and eventually enhances CBP-induced apoptosis.To promote the clinical transformation of S63845, we developed follicle-stimulating hormone-modified liposome nanoparticles (S63845@Lipo-FSH) to enhance stability, membrane penetration, and tumor-targeting capabilities. S63845@Lipo-FSH exhibits a superior therapeutic efficacy and tumor targeting compared to free S63845, even when the dose of S63845 is reduced to one-fifth. Overall, targeting MCL1 by S63845@Lipo-FSH enhances CBP efficiency in ovarian cancer, with safety and efficacy, suggesting that this strategy is effective and promising for clinical application.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"59 ","pages":"Article 102513"},"PeriodicalIF":13.2,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0