查找使用阿拉丁产品的科研文献

Enzyme/pH dual stimuli-responsive nanoplatform co-deliver disulfiram and doxorubicin for effective treatment of breast cancer lung metastasis

Peifu Xiao,Xiaoguang Tao,Hanxun Wang,Hongbing Liu,Yupeng Feng,Yueqi Zhu,Zhengzhen Jiang,Tian Yin,Yu Zhang,Haibing He,Jingxin Gou,Xing Tang

Ultrasound-Chargeable Persistent Luminescence Nanoparticles to Generate Self-Propelled Motion and Photothermal/NO Therapy for Synergistic Tumor Treatment

Zhanlin Zhang,Hui Yan,Wenxiong Cao,Shuang Xie,Pan Ran,Kun Wei,Xiaohong Li

Cancer phototherapy indicates advantages in ease of manipulation, negligible drug resistance, and spatiotemporal control but is confronted with challenges in tumor cell accessibility and intermittent light excitation. Herein, we propose a strategy with persistent luminescence (PL)-excited photothermal therapy (PTT), concurrent thermophoresis-propelled motion, and PL-triggered NO release, where PL emission is chargeable by ultrasonication for readily applicable to deep tumors. Mechanoluminescent (ML) nanodots of SrAl2O4:Eu2+ (SAOE) and PL nanodots of ZnGa2O4:Cr3+ (ZGC) were deposited on mesoporous silicates to obtain mSZ nanoparticles (NPs), followed by partially coating with polydopamine (PDA) caps and loading NO donors to prepare Janus mSZ@PDA-NO NPs. The ML emission bands of SAOE nanodots overlap with the excitation band of ZGC, and the persistent near-infrared (NIR) emission could be repeatedly activated by ultrasonication. The PL emission acts as an internal NIR source to produce a thermophoretic force and NO gas propellers to drive the motion of Janus NPs. Compared with the commonly used intermittent NIR illumination at both 660 and 808 nm, the persistent motion of ultrasound-activated NPs enhances cellular uptake and long-lasting PTT and intracellular NO levels to combat tumor cells without the use of any chemotherapeutic drugs. The ultrasound-activated persistent motion promotes intratumoral accumulation and tumor distribution of PTT/NO therapeutics and exhibits significantly higher tumor growth inhibition, longer animal survival, and larger intratumoral NO levels than those who experience external NIR illumination. Thus, this study demonstrates a strategy to activate PL emissions and construct PL-excited nanomotors for phototherapy in deep tissues.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells

Xuan Nie,Wei You,Ze Zhang,Fan Gao,Xiao-Hong Zhou,Hai-Li Wang,Long-Hai Wang,Guang Chen,Chang-Hui Wang,Chun-Yan Hong,Qi Shao,Fei Wang,Lei Xia,Yang Li,Ye-Zi You

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

A biomimetic mineralization nanosystem based on glycolysis-oxidative stress-autophagy regulation for the suppression of malignant tumor and lung metastasis

Ping Guan,Zhaoxu Meng,Xinran Liu,Jiaxiang Mu,Zichun Gao,Xinrong Yu,He Lian

The complex, invasive, and metastatic nature of malignant tumors make the current treatment of patients challenging in advanced stages. The present study proposes a multi-effect synergistic biomimetic mineralization nanosystem ( [email protected] 4 ) to regulate tumor cell metabolism and relevant biological behaviors through glycolysis-oxidative stress-autophagy process. Bovine serum albumin complexed with lonidamine served as a template to induce the formation of iron phosphate mineralization in situ . After intratumoral administration, the released lonidamine inhibited hexokinase II and down-regulated the level of glycolysis, cutting off the energy and biosynthesis supply source for tumor growth. Ferric ions dissociated from biomineralization in acidic microenvironment converted reduced glutathione to oxidized glutathione, elevated oxidative stress and induced ferroptosis through chemokinetic reactions. The dissociated phosphate ions function as an autophagy inhibitor to block the protective autophagy cased by energy deprivation for efficacy enhancement. The up-regulation of Nrf2 and LC3 proteins, the down-regulation of HK2 and GPX4 proteins, and the increase of ROS level in tumors all confirmed this conclusion. Notably, the nanosystem also down-regulated the release of inflammatory factors (IL-6, IL-8) and metastasis-related proteins (N-Cadherine, Vimentin) simultaneously, effectively preventing distant lung metastasis of tumor. In summary, this biomineralization-based nanosystem exhibited powerful antitumor effects both in vitro and in vivo and provides a new perspective for addressing the dilemma of malignant tumor treatment.

Red blood cell membrane-coated functionalized Au nanocage as a biomimetic platform for improved MicroRNA delivery in hepatocellular carcinoma

Shengnan Huang,Chengzhi Song,Jinxin Miao,Xiali Zhu,Yongyan Jia,Yafei Liu,Dongjun Fu,Benyi Li,Mingsan Miao,Shaofeng Duan,Zhenzhong Zhang,Yurong Hu

Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo . Herein, a novel biomimetic platform designated as RHAuNCs-miRNA for improved miRNA delivery was prepared through wrapping miRNA-loaded functionalized Au nanocages (AuNCs) with red blood cell (RBC) membrane. RHAuNCs-miRNA not only successfully loaded miRNAs but also effectively protected them from enzymatic degradation. With good stability, RHAuNCs-miRNA had the characteristics of photothermal conversion and sustained release. Cellular uptake of RHAuNCs-miRNA by SMMC-7721 cells was in a time-dependent manner via clathrin- and caveolin-mediated endocytosis. The uptake of RHAuNCs-miRNAs was affected by cell types and improved by mild near infrared (NIR) laser irradiation. More importantly, RHAuNCs-miRNA exhibited a prolonged circulation time without the occurrence of accelerated blood clearance (ABC) in vivo, resulting in efficient delivery to tumor tissues. This study may demonstrate the great potential of RHAuNCs-miRNA for improved miRNAs delivery.

Determination of ten antipsychotics in blood, hair and nails: Validation of a LC–MS/MS method and forensic application of keratinized matrix analysis

Huanhuan Yang,Cong Liu,Chuanhong Zhu,Yan Zheng,Juan Li,Qianyun Zhu,Hao Wang,Xiangming Fang,Quan Liu,Man Liang,Zilong Liu

Determination of antipsychotics from biological samples is meaningful in the field of clinical and forensic medicine. Compared to blood, keratinized matrices such as hair and nails have attracted increasing attention in drug analysis for wider detection window. Nevertheless, the distribution and stability of antipsychotics in keratinized matrices are not clarified yet. Therefore, we developed a LC-MS/MS based method for simultaneous determination of 10 antipsychotics from blood, hair and nails, with high recovery (78.1–107.4%, 71.3–93.5% and 75.2–90.5%), low LOD (5–10 pg/mL, 5–10 pg/mg and 5 pg/mg) and high accuracy (96.0%−101.6%, 97.5%−102.5% and 97.6–101.7%). The method was applied to sets of blood, hair, and nail samples of 54 patients who received long-term therapy, and significant correlations between drug concentrations in blood and hair was found, while the correlation between nails and other matrices varied depending on the drug. Except for olanzapine , the concentrations of antipsychotics in segmental hair samples were consistent with drug exposure. Besides, the hair and nail samples of suspects in two forensic cases were analyzed and provided supporting evidence for the suspects’ psychiatric state. Our research offered a deeper understanding of keratinized matrix as stable and retrospective bio-samples for antipsychotics detection in forensic practice.

Near-infrared targeted EGFR fluorescent probe for tumor imaging and diagnosis

Wenjing Huang,Li Wang,Hao Zhang,Zhihao Han,Yueqing Gu

The incidence of prostate cancer has increased rapidly in recent years. And the detection of tumor markers is an effective way for early diagnosis and poor prognosis. Prostate cancer is associated with growth factor receptors. Epidermal growth factor receptor (EGFR) expression is increased in a majority of prostate cancer patients. Peptide probes have the advantages of convenient modification and selective and rapid clearance in the molecular imaging of tumors. H1 is a short peptide designed and modified based on the CDR3 region of a nanobody targeting the epidermal growth factor receptor (EGFR) with high affinity for malignant tumors that overexpress EGFR. The CDR3 sequence of nanobodies has a long finger-like structure that allows deep interaction with the cryptic epitope of the antigen. Here we synthesized a sensitive fluorescent peptide probe of H1 conjugated to imaging moieties MPA. Experimental data showed that H1-MPA targets EGFR with high affinity. Meanwhile, H1-MPA has high tumor uptake and a strong signal-to-noise ratio. In addition, the near-infrared fluorescent probe H1-MPA can determine tumor boundaries and can be used to monitor and prevent tumor metastasis, including hepatic metastasis, for accurate tumor diagnosis. H1-MPA provides a promising tool for cancer diagnosis.

Preparation of magnetic molecularly imprinted polymers for selective extraction of xylazine in milk

Cen Chen,Yuhang Zhang,Yulong Tang,Guangrong Huang,Han Jiang

Summary Magnetic molecularly imprinted polymers (MMIPs) were prepared by surface precipitation polymerisation, which used xylazine as its template molecule and Fe 3 O 4 as its support. The characterisation analysis and adsorption experiments of MMIPs were carried out. At the same time, promethazine, chlorpromazine, trifluoperazine, acepromazine and perphenazine were selected as structural analogues for selective experiments. The results showed MMIPs were successfully prepared with small particle size, excellent magnetic and thermal stability, high adsorption capacity and selectivity for xylazine. The maximum adsorption capacity of MMIPs for xylazine was 4.2017 mg g −1 , and the adsorption reached binding equilibrium within 30 min. The magnetic solid phase extraction (MSPE) based on MMIPs and traditional solid phase extraction (SPE) based on SPE column for xylazine in milk samples were compared and xylazine was analysed by HPLC. Although the difference between the two SPE methods was not significant, the MSPE method procedure took only about 35 min, which was faster than the traditional SPE method (>100 min), and the MSPE method had lower LOD (2.62 ng mL −1 ). MSPE has the advantages of simple operation, short extraction time, low cost and friendly to the environment, it has good application potential in the detection of xylazine in milk samples.

Photothermal Propelling and Pyroelectric Potential-Promoted Cell Internalization of Janus Nanoparticles and Pyroelectrodynamic Tumor Therapy

Junwu Wei,Yuan Liu,Yingxin Li,Zhanlin Zhang,Jie Meng,Shuang Xie,Xiaohong Li

Cancer phototherapy experiences limitations in tissue diffusion and cell internalization of phototherapeutic agents and dose-dependent side effects. Herein, Janus pyroelectric nanoparticles (NPs) are designed to generate self-powered motion and built-in electric fields to overcome the delivery barriers. Polydopamine (PDA) layers are partially coated on tetragonal BaTiO 3 (tBT) NPs to prepare Janus tBT@PDA, and Au NPs are deposited on the PDA caps to obtain Janus tBT@PDA-Au NPs. Near-infrared (NIR) illumination of tBT@PDA-Au builds in situ pyroelectric potentials on NPs, which selectively affect the membrane potential of tumor cells rather than normal cells to enhance tumor cell internalization and produce reactive oxygen species (ROS) for pyroelectric dynamic therapy (PEDT). The asymmetric photothermal effect of the Janus NPs creates thermophoretic force to propel NP motion, which enhances tumor diffusion and cellular uptake of NPs and boosts cytotoxicity and intracellular ROS levels. The inoculation of Au NPs increases the photothermal effect, exhibits larger motion velocities, produces higher pyroelectric potentials, and elevates cellular uptake rates, resulting in significant induction of tumor cell apoptosis, suppression of tumor growth, and extension of animal survival. Thus, the concise design of tBT@PDA-Au/NIR treatment has achieved thermophoretic motion-promoted tissue diffusion, built-in electric field-enhanced cell internalization, and photothermal/PEDT-synergized antitumor efficacy.

Rational synthesis of carbon dots with phosphate ester group for direct mapping of endogenous alkaline phosphatase and polarity monitoring in living cells

Yanzhi Xing,Yulong Xu,Yanna Lin,E Shuang,Han Leng,Jianhua Wang,Xuwei Chen

Carbon dots (CDs) have been extensively employed in biomolecule imaging. However, the imaging of biological enzymes with CDs has not been reported, which greatly limits their application in biological imaging. Herein, for the first time, a new type of fluorescent CDs is elaborately designed to realize the direct mapping of alkaline phosphatase (ALP) in cells. The obtained phosphorus and nitrogen co-doped CDs (P, N-CDs) generate specific structures including xanthene oxide and phosphate ester, thereby enabling P, N-CDs to be exclusively cleaved by ALP without auxiliary media. The fluorescence intensity of P, N-CDs can be specifically turned on in the presence of ALP, making them powerful probes for sensitive sensing of ALP activity with a detection limit of 1.27 U·L − 1 . Meanwhile, P, N-CDs possessing electron deficiency structure fulfill sensitive responding to polarity variations. The excellent photo-bleaching resistance and biocompatibility of the P, N-CDs are taken for directly mapping the intracellular endogenous ALP via turned-on fluorescence imaging, as well as real-time monitoring the polarity fluctuation in cells through ratiometric fluorescence imaging. The present work offers a new way to design and synthesize functional CDs for direct imaging of intracellular enzymes.

Efficient transfected liposomes co-loaded with pNrf2 and pirfenidone improves safe delivery for enhanced pulmonary fibrosis reversion

Xin Chang,Chang Liu,Yu-Mo Han,Qiu-Ling Li,Bin Guo,Hu-Lin Jiang

Pulmonary fibrosis (PF) is an interstitial lung disease with complex pathological mechanism, and there is currently a lack of therapeutics that can heal it completely. Using gene therapy with drugs provides promising therapeutic strategies for synergistically reversing PF. However, improving the intracellular accumulation and transfection efficiency of therapeutic nucleic acids is still a critical issue that urgently needs to be addressed. Herein, we developed lipid nanoparticles (PEDPs) with high transfection efficiency coloaded with pDNA of nuclear factor erythroid 2-related factor 2 (pNrf2) and pirfenidone (PFD) for PF therapy. PEDPs can penetrate biological barriers, accumulate at the target, and exert therapeutic effects, eventually alleviating the oxidative stress imbalance in type II alveolar epithelial cells (AECs II) and inhibiting myofibroblast overactivation through the synergistic effects of Nrf2 combined with PFD, thus reversing PF. In addition, we systematically engineered various liposomes (LNPs), demonstrated that reducing the polyethylene glycol (PEG) proportion could significantly improve the uptake and transfection efficiency of the LNPs, and proposed a possible mechanism for this influence. This study clearly reveals that controlling the composition ratio of PEG in PEDPs can efficiently deliver therapeutics into AECs II, improve pNrf2 transfection, and synergize with PFD in a prospective strategy to reverse PF.

Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting

Yajing Wang,Ziwei Ding,Shiqun Lv,Jie Liu,Jie Pan,Yingcong Yu,Jun Gao,Xianfeng Huang