iScience
·
2024
·
IF 4.6
Lele Xu,Yuting Chen,Tao Wu,Jiaqi Fan,Yuying Hu,Xuefeng Gao,Yuliang Wang,Tao Chen,Xueting Zhao,Min Zeng,Fei Wang,Qingyou Zheng,Xiaojuan Pei,Dinglan Wu
Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) represent a promising novel treatment for castration-resistant prostate cancer (CRPC) with encouraging results. However, the combination targets in CRPC remain largely unexplored. N6-methyladenosine (m 6 A) has been shown to play a crucial role in cancer progression and DNA damage response. Here, we observed a higher overall level of m 6 A and a downregulation of Fat mass and obesity-associated protein (FTO), which correlated with unfavorable clinicopathological parameters in prostate cancer (PCa). Functionally, reduced FTO promotes PCa growth, while overexpression of FTO has the opposite effect. Mechanistically, FOXO3a was identified as the downstream target of FTO in PCa. FTO downregulates the expression of FOXO3a in an m 6 A-dependent manner, leading to the degradation of its mRNA. Importantly, DNA damage can degrade FTO through the ubiquitination pathway. Finally, we found that overexpression of FTO can enhance the effect of PARPi on PCa. Therefore, our findings may provide insight into novel therapeutic approaches for CRPC.
研究领域:
癌症生物学
·
分子生物学
·
表观遗传学
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Xiang Feng,Yunfeng Zhou,Xin Xie,Ming Li,Hao Huang,Liangliang Wang,Xiao Xu,Jingmou Yu
In this study, prostate-specific membrane antigen (PSMA)-targeted and core-crosslinked micelles were developed based on prostate cancer-binding peptide (PCP) modified glycol chitosan-lipoic acid (PGC-LA) conjugate. The degree of substitution was 5.2 PCP groups and 10.7 lipoic acid groups per 100 sugar residues of glycol chitosan in PGC-LA copolymer. Docetaxel (DTX) was chosen as a model anti-tumor drug. The DTX-loaded micelles were prepared by an o/w method, and core-crosslinked micelles were further constructed by using a catalytic amount of dithiothreitol. The mean diameter of DTX-loaded core-crosslinked PGC-LA (DTX-PGC-LA/cc) micelles was 397 nm determined by dynamic light scattering (DLS). In vitro DTX released from core-crosslinked micelles was slower than that from non-crosslinked counterpart. Blank micelles exhibited good biocompatibility. Additionally, cellular uptake and cytotoxcity of PCP-modified micelles were higher than those of micelles without PCP in PSMA-positive LNCaP cells. Importantly, DTX-PGC-LA/cc demonstrated the stronger anti-tumor efficacy against LNCaP tumor xenograft models than DTX injection and other DTX-loaded micelles. Taken together, this study provides a potential way in developing actively targeted and core-crosslinked micelles for hydrophobic drug delivery in cancer therapy.
研究领域:
药剂学
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肿瘤学
·
生物医学工程
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DOI
PubMed
高影响因子
RSC Advances
·
2024
·Vol. 14
·期 47
·34848-34854
·
IF 3.9
Mutu Lin,Qiaohong Wang,Yun Dai,Jinyuan Chen,Yiming Lin
A highly sensitive and efficient home-use method is impressive and promising in the self-monitoring of chronic prostatitis (CP). Herein, we developed a glucose oxidase-zeolitic imidazolate framework-8-antibody composite (GOx@ZIF-8@Ab2) to achieve highly sensitive point-of-care testing (POCT) of urinary prostatic exosomal protein (PSEP) by combining it with a personal glucometer (PGM). The developed GOx@ZIF-8@Ab2 was prepared through a simple but effective biomineralization reaction and a strong binding affinity between Zn2+ and Fc region of the antibody. This bifunctional material GOx@ZIF-8@Ab2 could not only specifically recognize the PSEP via immunoreaction but also wrap a large number of GOx molecules. Following the sandwich immunoreaction, the prepared GOx@ZIF-8@Ab2 facilitated hydrolysis of glucose in a one-to-many fashion, amplifying the detection signal and greatly improving the sensitivity of PGM detection. In comparison to those of the conventional enzyme-linked immunosorbent assay (ELISA), the detection time of the developed technique was shortened to 45 minutes and its limit of detection (0.23 pg mL−1) was reduced by 4–5 orders of magnitude. This technique was successfully utilized for detecting PSEP in human urine samples with a recovery rate of 96–116%. Owing to its rapid, ultrasensitive, specific and portable features, the as-designed platform based on GOx@ZIF-8@Ab2 and the PGM device holds great promise as a home-use POCT platform for self-monitoring of CP and other chronic diseases.
研究领域:
医学诊断
·
生物材料科学
·
分析化学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2018
·
IF 4.556
Qingzhi Lv,Jincheng Yang,Ruoshi Zhang,Zimeng Yang,Zhengtao Yang,Yongjun Wang,Youjun Xu,Zhonggui He
Prostate cancer (PCa) is the most prevalent cancer among men in the United States and remains the second-leading cause of cancer mortality in men. Paclitaxel (PTX) is the first line chemotherapy for PCa treatment, but its therapeutic efficacy is greatly restricted by the nonspecific distribution in vivo. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of most PCa cells, and its expression level increases with cancer aggressiveness, while being present at low levels in normal cells. The high expression level of PSMA in PCa cells offers an opportunity for target delivery of nonspecific cytotoxic drugs to PCa cells, thus improving therapeutic efficacy and reducing toxicity. PSMA has high affinity for DUPA, a glutamate urea ligand. Herein, a novel DUPA–PTX conjugate is developed using DUPA as the targeting ligand to deliver PTX specifically for treatment of PSMA expressing PCa. The targeting ligand DUPA enhances the transport capability and selectivity of PTX to tumor cells via PSMA mediated endocytosis. Besides, DUPA is conjugated with PTX via a disulfide bond, which facilitates the rapid and differential drug release in tumor cells. The DUPA–PTX conjugate exhibits potent cytotoxicity in PSMA expressing cell lines and induces a complete cessation of tumor growth with no obvious toxicity. Our findings give new insight into the PSMA-targeted delivery of chemotherapeutics and provide an opportunity for the development of novel active targeting drug delivery systems for PCa therapy.
研究领域:
肿瘤学
·
药学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Lu Zhou,Ye Liu,Fuyan Wang,Zhijian Jia,Jun Zhou,Tao Jiang,Lucia Petti,Yichen Chen,Qi Xiong,Xiaojun Wang
Prostate cancer (PCa) is a leading cause of cancer-related death among males globally. To date, prostate-specific antigen (PSA), as a typical tumour marker, has been widely used in the early diagnosis of PCa. However, in practical clinical tests, high serum levels of PSA show a high probability for false-positive results, leading to misdiagnoses. In this study, we developed a new classification system for PCa, benign prostate hyperplasia (BPH) and healthy subjects by using a surface-enhanced Raman scattering (SERS)-based immunoassay of multiple tumour markers along with a support vector machine (SVM) algorithm. Silver nanoparticles (AgNPs) as immune probes and SiC@Ag@Ag-NPs SERS as immune substrates were constructed into a sandwich structure to serve as an ultrasensitive SERS-based immunoassay platform of tumour markers. With this assay, the limits of detection for PSA, prostate-specific membrane antigen (PSMA) and human kallikrein 2 (hK2) were as low as 0.46 fg mL −1 , 1.05 fg mL −1 and 0.67 fg mL −1 , respectively. Furthermore, the serum levels of PSA, PSMA and hK2 in clinical samples were successfully detected using the SERS-based immunoassay platform, and correct classifications of PCa, BPH and healthy subjects were feasible with help of the linear SVM algorithm. These results demonstrate the potential for improving the diagnostic accuracy of PCa. Overall, the linear SVM classification model with multiple tumour markers exhibited good classifications of PCa, BPH and healthy subjects, with a PCa diagnostic accuracy of 70% that was significantly superior to that of the linear SVM classification model based only on the serum level of PSA (50%). Therefore, combining the SERS-based immunoassay with pattern recognition technology can allow for comprehensive analyses of the serum levels of multiple tumour markers to effectively improve the diagnostic accuracy of cancer with potential applications in point-of-care testing.
研究领域:
医学诊断
·
生物传感
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2022
·
IF 5.738
Ren Ya’nan,Liu Chen,Liu Teli,Duan Xiaojiang,Zhang Qian,Liu Jiayue,Wang Pei,Guo Qian,Yang Xing,Du Peng,Zhu Hua,Yang Zhi
Purpose: This study aimed to introduce a novel [18F]AlF-labeled ODAP-Urea-based Prostate-specific membrane antigen (PSMA) probe, named [18F]AlF-PSMA-137, which was derived from the successful modification of glutamate-like functional group. The preclinically physical and biological characteristics of the probe were analyzed. Polit clinical PET/CT translation was performed to analyze its feasibility in clinical diagnosis of prostate cancer.Methods: [18F]AlF-PSMA-137 was maturely labeled with the [18F]AlF2+ labeling technique. It was analyzed by radio-HPLC for radiochemical purity and stability analysis in vitro and in vivo. The PSMA specificity was investigated in PSMA-positive (LNCaP) and PSMA-negative (PC3) cells, and the binding affinity was evaluated in LNCaP cells. Micro-PET/CT imaging was performed in mice bearing LNCaP or PC3 tumors. Thirteen patients with newly diagnosed prostate cancer were included for [18F]AlF-PSMA-137 PET/CT imaging. Physiologic biodistribution and tumor burden were semi-quantitatively evaluated and the radiation dosimetry of [18F]AlF-PSMA-137 was estimated.Results: The radiochemical yield of [18F]AlF-PSMA-137 was 54.2 ± 10.7% (n = 16) with the radiochemical purity over 99% and the specific activity of 26.36 ± 7.33 GBq/μmol. The binding affinity to PSMA was 2.11 ± 0.63 nM. [18F]AlF-PSMA-137 showed high cell/tumor uptake which can be specifically blocked by PSMA inhibitor. According to the biodistribution in patients, [18F]AlF-PSMA-137 was mainly accumulated in kidneys, lacrimal glands, parotid glands, submandibular glands and liver which was similar to the extensive Glu-Ureas based probes. A total of 81 lesions were detected in PET/CT imaging and over 91% of lesions increased between 1 h p.i. (SUVmean: 10.98 ± 18.12) and 2 h p.i. (SUVmean: 14.25 ± 21.28) (p < 0.001). Additionally, the probe showed intensive accumulation in lesions which provided excellent imaging contrast with the high tumor-to-muscle ratio of 15.57 ± 27.21 at 1 h p.i. and 25.42 ± 36.60 at 2 h p.i. (p < 0.001), respectively. The effective dose of [18F]AlF-PSMA-137 was estimated as 0.0119 ± 0.0009 mSv/MBq.Conclusion: An ODAP-Urea-based PSMA probe [18F]AlF-PSMA-137 was successfully prepared with high specificity and binding affinity to PSMA. Micro-PET/CT imaging study demonstrated its feasibility for prostate cancer imaging. Pilot clinical study showed its potential for delay-imaging and prostate cancer detection.
研究领域:
医学影像学
·
肿瘤学
·
放射化学
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Xiaohong Li,Basen Li,Muhammad Wajid Ullah,Raju Panday,Jiameng Cao,Qiubai Li,Yaopeng Zhang,Liang Wang,Guang Yang
Prostatic artery embolization (PAE) has been a well-established treatment for benign prostatic hyperplasia (BPH). To enhance the therapeutic efficacy, a strategy is to use embolic agent preloaded with 5α-reductase inhibitors for localized drug delivery. In this study, finasteride (FNS) was encapsulated into the polyvinyl alcohol (PVA) nanofibers via co-electrospinning technique, followed by heat treatment and cryogenic grinding to convert them into nanofibrous particles as a drug-loaded embolic agent. The FNS was found to be distributed uniformly in PVA nanofibers, and the processed FNS/PVA nanofibrous particles were 272 μm in mean particle size. Besides, the studies on the composition, thermal properties, swelling ratio, and water stability of the nanofibers and drug showed that the FNS remained its crystalline state in PVA nanofibers. The heat treatment increased the crystallinity of nanofibers and rendered them water stability. Both FNS and PVA possessed excellent thermal stability at high temperature (150 °C). In addition, in vitro drug release studies suggested the FNS followed a favorable sustained release up to 744 h. Furthermore, the cell viability and hemocompatibility assays indicated the nanofibers possessed excellent cytocompatibility and with no evidence of hemolysis. More importantly, the in vivo PAE procedures on beagles demonstrated the crosslinked FNS/PVA nanofibrous particles exhibited higher embolization efficacy with more obvious prostate volume (PV) reduction compared to crosslinked PVA nanofibrous particles after embolization for 1, 3, and 6 months ( P < 0.05). Therefore, such drug-loaded PVA nanofibrous particles combined physical embolization and localized medical therapy together, which offer great potential to be used as an effective embolic agent for BPH therapy.
研究领域:
医学
·
生物材料学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Dong Chen,Yilin Ma,Annan Yang,Liping Hu,Hanlin Zhou,Jun Xu,Shanze Chen,Dingmeng Nie,Weifeng Feng,Huaihong Cai,Yanguang Cong,Jiang Pi,Lang Rao,Xueqin Huang,Pinghua Sun,Haibo Zhou
Prostate specific antigen (PSA) is widely used in liquid biopsy of prostate cancer (PCa) but still faces challenges due to the poor specificity. Herein, this study reports a double-SERS satellite immunoassay, made of an Au–Ag dealloyed intra-nanogap nanoflower (Au–Ag DINF) with strong SERS signals and Au magnetic nanoparticles (AuMNPs) with magnetic capture and SERS amplification, for sensing multiple PSA (free PSA (fPSA), complexed PSA (cPSA) and [-2]proPSA (p2PSA)) toward potential PCa screening. Unlike the previous studies focus on the tPSA and fPSA/tPSA ratio (f/t PSA%), this work introduces a multiple PSA-mediated Prostate Health Index (PHI) assay with significantly increased the predictive accuracy and specificity of PCa, especially the patients with a tPSA level in the “diagnostic gray zone”. Practical analysis of clinical samples demonstrated the SERS immunoassay is capable of identifying the PCa subjects from healthy candidates ( N = 13), and monitoring PCa patients before and after surgery ( N = 5), as well as screening suspicious ones who are in the “gray zone” ( N = 10). Overall, benefiting from the PSA-responsive satellite immuno-nanoassemble strategy, dual-SERS magnification effect, and multiple PSA-based PHI assessment, this proposes bioassay held enormous potential for the early diagnosis, screening, monitoring, and prognosis of PCa.
研究领域:
医学诊断
·
纳米生物技术
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
APOPTOSIS
·
2024
·Vol. 29
·期 9
·1679-1695
·
IF 6.1
Fan Aoyu,Li Yunpeng,Zhang Yunyan,Meng Wei,Pan Wei,Chen Meixi,Ma Zhongliang,Chen Wei
Prostate cancer (PCa) is one of the most common cancers affecting the health of men worldwide. Castration-resistant prostate cancer (CRPC), the advanced and refractory phase of prostate cancer, has multiple mechanisms of resistance to androgen deprivation therapy (ADT) such as AR mutations, aberrant androgen synthase, and abnormal expression of AR-related genes. Based on the research of the AR pathway, new drugs for the treatment of CRPC have been developed in clinical practice, such as Abiraterone and enzalutamide. However, many areas in this pathway are still worth exploring. In this study, single-cell sequencing analysis was utilized to scrutinize significant genes in the androgen receptor (AR) pathway related to CRPC. Our analysis of single-cell sequencing combined with bulk-cell sequencing revealed a substantial downregulation of AR-regulated AFF3 in CRPC. Overexpression of AFF3 restricted the proliferation and migration of prostate cancer cells whilst also increasing their sensitivity towards enzalutamide, while knockdown of AFF3 had the opposite effect. To elucidate the mechanism of tumor inhibition by AFF3, we applied GSVA and GSEA to investigate the metabolic pathways related to AFF3 and revealed that AFF3 had an impact on fatty acids metabolism and ferroptosis through the regulation of ACSL4 protein expression. Based on correlation analysis and flow cytometry, we can speculate that AFF3 can impact the sensitivity of the CRPC cell lines to the ferroptosis inducer (RSL3) by regulating ACSL4. Therefore, our findings may provide new insights into the mechanisms of drug resistance in CRPC, and AFF3 may serve as a novel prognostic biomarker in prostate cancer.
研究领域:
肿瘤学
·
分子生物学
·
基因组学
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DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2022
·Vol. 18
·期 1
·158-165
·
IF 3.641
Wang Ruizhi,Zhou Guofeng,Yang Yuchan,Wang Shiqing,Gao Shanshan,Gao Dongmei,Wang Xiaolin
The advantages of deep tissue penetration and the high spatial accuracy of photothermal therapy have been widely studied. Gold, as a photothermal material, has received particular attention. Different sizes and shapes of gold have been studied and characterized for their varying photothermal
properties. The core–shell structure of gold nanoparticles and silica enhances the photothermal conversion through the coupling effect between gold clusters on the material’s surface. With excellent photothermal conversion performance, the core–shell nanoparticles can quickly
reach 40 °C in 200 s under the irradiation of 808 nm, 1.5 W·cm−2. The highest conversion temperature of these nanoparticles is 56 °C, and the photothermal conversion rate is 45%. In vitro cell experiments displayed that NPs with targeted function can
efficiently aggregate in prostate cancer cells and effectively kill cells. In vitro experiments showed that the tumor cells of mice after photothermal treatment completely disappeared after 15 days, which fully demonstrated the potential of the nanoparticles for targeted photothermal
therapy.
研究领域:
癌症治疗
·
纳米技术
·
材料科学
·
生物医学工程
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Aoyu Fan,Yunyan Zhang,Yunpeng Li,Wei Meng,Fan Wu,Wei Pan,Zhongliang Ma,Wei Chen
Prostate cancer (PCa) is one of the most common malignancies for male individuals globally. Androgen deprivation therapy (ADT) initially demonstrated significant efficacy in treating PCa; however, most cases of PCa eventually progress to castration-resistant prostate cancer (CRPC), which becomes increasingly challenging to manage. Notably, the loss or disruption of primary cilia in PCa cells may play a critical role in the progression of the disease, and there are no reports on the role of circular RNAs in ciliogenesis. Thus, this warrants further investigation.In this study, key circular RNAs linked to prostate cancer progression, and enzalutamide resistance is identified. Specifically, it is found that hsa_circ_0005185 interacts with OTUB1 and RAB8A, serving as a molecular scaffold. Hsa_circ_0005185 mediates the binding of the deubiquitinase OTUB1 to RAB8A, resulting in the deubiquitination of RAB8A. Consequently, the stable expression of RAB8A promotes the regeneration of primary cilia and enhances the production of GLI3R, an inhibitory factor in the Hedgehog signaling pathway, thereby suppressing AR activity and slowing the progression of CRPC.
研究领域:
肿瘤学
·
分子生物学
·
癌症遗传学
·
信号转导
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DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xinyu Shan,Xiang Li,Zhenyu Luo,Qing Lin,Yichao Lu,Mengshi Jiang,Junlei Zhang,Jiaxin Huang,Lin Xie,Xuemeng Guo,Xu Liu,Yingying Shi,Yu Liu,Hang Yin,Fuchun Yang,Lihua Luo,Jian You
When it comes to long-acting injections, lyotropic liquid crystals (LLCs) are considered as an effective and powerful drug delivery technology due to their low manufacturing and injection difficulty, consistent releasing behaviors with low burst, as well as broadly applicable drug loading capacity. However, monoolein and phytantriol, as two widely used LLC-forming materials, may give rise to tissue cytotoxicity and undesired immunological responses, which may hinder the wide application of this technology. In this study, we opted for two ingredients, phosphatidylcholine and α-tocopherol, as carriers on account of their nature-obtainable and biocompatible qualities. By changing the ratios between them, we conducted research on crystalline types, nanosized structures, viscoelastic differences, characteristics of releasing behaviors, and in vivo safety. To fully exploit this in situ LLC platform with both injectability and sprayability, we focused on the treatment of both hormone-sensitive (HSPC) and castration-resistant prostate cancer (CRPC). For HSPC, we found that spraying leuprolide and a cabazitaxel-loaded LLC platform on the tumor bed after resection greatly reduced tumor metastatic rate and prolonged the survival time. Besides, for CRPC, our results demonstrated that although leuprolide (a kind of drug for castration) alone could hardly limit the progression of CRPC with low MHC-I expression, its combination with cabazitaxel in our LLC platform achieved a significantly better tumor-inhibiting and anti-recurrent efficacy than single cabazitaxel-loaded LLC platform, owing to enhanced CD4+ T cell infiltration in tumors and immune-potentiating cytokines. In conclusion, our dual-functional and clinically achievable strategy might provide a treating solution toward both HSPC and CRPC.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
生物医学工程
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）