Small
·
2024
·
IF 13
Zhoujiang Chen,Lianlin Long,Ji Wang,Mingli Jiang,Wei Li,Wenguo Cui,Liang Zou
The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.58%, coupled with acid-sensitive drug release characteristics. Notably, ECM-DOX nanoparticles enhance the uptake by tumor cells and possess the ability to penetrate endothelial cells and infiltrate tumor multicellular spheroids. Mechanistic insights reveal that the internalization of ECM-DOX nanoparticle is facilitated through clathrin-mediated endocytosis and macropinocytosis, intricately involving hyaluronic acid receptors and integrins. Pharmacokinetic assessments unveil a prolonged blood half-life of ECM-DOX nanoparticles at 3.65 h, a substantial improvement over the 1.09 h observed for free DOX. A sustained accumulation effect of ECM-DOX nanoparticles at tumor sites, with drug levels in tumor tissues surpassing those of free DOX by several-fold. The profound therapeutic impact of ECM-DOX nanoparticles is evident in their notable inhibition of tumor growth, extension of median survival time in animals, and significant reduction in DOX-induced cardiotoxicity. The ECM platform emerges as a promising carrier for avant-garde nanomedicines in the realm of cancer treatment.
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CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Jie Meng,Wei Wei,Shuang Xie,Junwu Wei,Zhanlin Zhang,Pan Ran,Xiaohong Li
Pyroelectrodynamic therapy (PEDT) has emerged as an attractive therapeutic modality for tumors, but is dramatically discounted by inherent defects of wide band gap, fast electron − hole recombination and low photothermal utilization. Herein, hollow-structured Janus nanoparticles (NPs) are developed to improve tumor accumulation and PEDT generation of reactive oxidative species (ROS) for antitumor treatment. Hollow barium titanate (hBT) NPs were prepared by the template and hydrothermal method for in situ deposition of CuS nanodots and then partially coated with polydopamine (PDA) caps to obtain hBT-CuS@PDA. Finite element analysis reveals that the unique thin shell of hBT benefits transportation of pyroelectrically generated charge carriers through shortening diffusion distance to the interface. The CuS deposition forms heterojunctions with hBT to accelerate electron − hole separation and leads to a larger pyroelectric current. The hollow structure facilitates light absorption and conversion, and the photothermal effect of the half-coated PDA caps generates asymmetric temperature gradient to drive NP locomotion across biological barriers. The in situ generated pyroelectric field selectively affects membrane potential and fluidity of tumor cells to enhance the specific NP internalization. The pyroelectric effect enhances the peroxidase-like activity of CuS nanodots to generate toxic ·OH and the glutathione peroxidase-like activity to inhibit glutathione consumption of ROS. The integration of photothermal, pyroelectric, nanozyme catalysis and self-protrusion effects promotes NP accumulation and penetration throughout tumors to exhibit therapeutic effect at a mild-temperature, reducing the possible high-temperature ablation of normal tissues. The hollow and heterjunction structure generates abundant intracellular ROS and efficient diffusion in tumor tissues to inhibit tumor growth and extend animal survival, offering a safe and effective PEDT strategy.
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CHEMICAL ENGINEERING JOURNAL
·
2024
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IF 13.3
Yanzhi Xing,Jiaxin Li,Han Leng,Yanfeng Zhang,Shuang E,Jianhua Wang,Xuwei Chen
The interactions between various organelles play a crucial role on cellular activity, and the design and construction of multi-organelle fluorescent probes is of great challenges. Herein, fluorescent CDs with tunable cell plasma membrane and lipid-rich organelle-targeting ability were fabricated via exquisitely regulating the ratio of tridecanedioic acid and m -diethylaminophenol as the co-precursor, combining the structure–activity relationship to modulate the CDs structure and surficial property. Condensation of m -diethylaminophenol in the presence of different amount of tridecanedioic acid was exploited to construct MCDs and ECDs for targeted cell membrane and endoplasmic reticulum imaging respectively. The appropriately incorporated alkyl chains as membrane anchoring group and the suppressed internalization by carboxyl group led to the retention of MCDs in cell membrane, while the excessive introduction of alkyl chains offered ECDs with high lipophilicity, resulting in the rapid internalization and subsequential distribution in endoplasmic reticulum membrane. The favorable membrane retention capability and excellent photostability make MCDs an excellent probe for long-term targeted-imaging of cell membrane in vitro, with remarkable tracking duration long to five passages and effectively display cell membrane morphological dynamics during cell division and cell death. Moreover, real-time evaluation of cholesterol consumption of Lo phase in cell membrane via ratiometric fluorescence imaging was achieved, attributed to the sensitive response of CDs to polarity variations.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2024
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IF 8
Weiyi Lu,Bin Yang,Zihua Guo,Zhen Tian,Wenhui He,Tiancheng Yang
Phenothiazine drugs are widely used to treat psychotic diseases in humans. The phenothiazine ligand enables unique interaction between the drugs and DNA double helix. We discovered that it was impossible to select aptamer to selectively bind with phenothiazine drug. In this study, an alternative fluorescence sensor array was first developed to accurately discriminate four typical phenothiazine drugs based on machine learning. As the eight sensor elements, versatile DNA probes were designed based on different oligonucleotides , two unique fluorescence dyes , and diverse buffer solutions. The fingerprint data can offer the fluorescence response patterns against each phenothiazine drug. Linear discriminant analysis (LDA) can discriminate single one or mixture samples of phenothiazine drugs with 100% accuracy. Besides, one neural network model showed a good linear relationship between predicted and actual concentrations to quantitatively assay specific phenothiazine drugs. The proposed fluorescence sensor array presents a new way to accurately discriminate phenothiazine drugs in pharmacy or biology field.
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CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Junxi Liu,Xiaoke Zhang,Yan Liu,Zhijing Wu,Zheng Cui,Xianglin Pan,Yuheng Zheng,Jinglin Wang,Kaiping Wang,Yu Zhang
Recently, the intestinal lymphatic transport based on Peyer's patches (PPs) is emerging as a promising absorption pathway for natural polysaccharides. Herein, the aim of this study is to investigate the PP-based oral absorption of a pectic polysaccharide from Smilax china L. (SCLP), as well as its uptake and transport mechanisms in related immune cells. Taking advantages of the traceability of fluorescently labeled SCLP, we confirmed that SCLP could be absorbed into PPs and captured by their mononuclear phagocytes (dendritic cells and macrophages) following oral administration. Subsequently, the systematic in vitro study suggested that the endocytic mechanisms of SCLP by model mononuclear phagocytes (BMDCs and RAW264.7 cells) mainly involved caveolae-mediated endocytosis, macropinocytosis and phagocytosis. More importantly, SCLP directly binds and interacts with toll-like receptor 2 (TLR2) and galectin 3 (Gal-3) receptor, and was taken up by mononuclear phagocytes in receptor-mediated manner. After internalization, SCLP was intracellularly transported primarily through endolysosomal pathway and ultimately localized in lysosomes. In summary, this work reveals novel information and perspectives about the in vivo fate of SCLP, which will contribute to further research and utilization of SCLP and other pectic polysaccharides.
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AAPS PHARMSCITECH
·
2024
·Vol. 25
·期 8
·1-12
·
IF 3.4
Li Bo,Zhao Qianhui,Yang Hanyu,Wang Xueyuying,Zhang Zhijun,Gong Yanling,Wan Xu
Osteosarcoma (OS) is one of the most common primary bone sarcoma with high malignant degree and poor prognosis, for which there is an urgent need to develop novel therapeutic approaches. Recent research has revealed that mifamurtide significantly improved the outcome of OS patients when combined with adjuvant chemotherapy drugs including cisplatin (DDP). The present study aimed to construct a drug delivery system co-loading DDP and mifamurtide. Long-circulating targeted liposomes co-loading DDP and mifamurtide were constructed with Soy lecithin (SPC), cholesterol (Chol) and 1,2-distearoylglycero-3-phosphoethanolamine-n-[poly(ethyleneglycol)] (DSPE-PEG), modified with MMP14 targeting peptide BCY-B in the surface of liposomes. In addition to characterization, the cellular uptake, endocytosis pathway and inhibition on cell viability, migration, invasion and cell apoptosis of MG-63 cells were explored. The constructed liposomal delivery possessed the basic characteristics of liposomes and showed high affinity to MG-63 cells, resulting in high uptake efficiency in MG-63 cells. The endocytosis might be involved in multiple pathways including caveolae-mediated endocytosis, clathrin-mediated endocytosis and macropinocytosis, dependently on energy. The constructed long-circulating targeted liposomes co-loading DDP and mifamurtide significantly inhibited the cell viability, migration, invasion and cell apoptosis of MG-63 cells, improving the antitumor effect of DDP and mifamurtide in vitro . The constructed liposomal delivery system is suitable for co-loading DDP and mifamurtide to achieve active tumor targeting, supplying a new strategy for the treatment of OS. Graphical Abstract
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yadan Zhang,Xiaoyu Zhang,Tianhan Kai,Lin Zhang,Anping Li
Plant-derived exosome-like nanovesicles (ELNs) are nano-sized vesicles extracted from edible plants. Lycium ruthenicum Murray (LRM) has been gaining increasing attention due to its nutritional and medicinal value, but the ELNs in LRM has not been reported. In this study, LRM-ELNs were obtained, and the proteins, lipids, microRNAs (miRNAs) and active components in LRM tissues and LRM-ELNs was analyzed by LC-MS/MS, LC-MS, high-throughput sequencing techniques, and physical and chemical analysis. LRM-ELNs can be uptaken by PC12 cells through macropinocytosis and caveolin-mediated endocytosis primarily. Transcriptomic and western blot experiments indicate that LRM-ELNs can inhibit Aβ-induced apoptosis in PC12 cells through the MAPK and PI3K/AKT signaling pathways, with miRNAs playing a crucial role. These results indicate that LRM-ELNs have the protection effect on PC12 cells and can be considered as dietary supplements for alleviating neurodegenerative diseases.
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Advanced Science
·
2025
·
IF 14.1
Jinzhao Liu,Meicen Wu,Qingyang Lyu,Chang Yang,Ni Fan,Kang Chen,Weiping Wang
Immune evasion and metastasis are the leading causes of poor prognosis in triple-negative breast cancer treatment. Since current standard immunotherapies have limited efficacy due to immunologically cold microenvironment, it is crucial to explore new strategies to sensitize anticancer immune response. In this study, it is found that incorporating β -lapachone-based oxidation therapy with CUDC101-initiated epigenetic regulation results in synergistic antitumor effects and potent immune activation. To co-deliver these two hydrophobic drugs, IR783 with cyanine structure serves as the stabilizer to form a nanoformulation based on small molecule self-assembly. Such IR783-stabilized nanodrugs can not only lead to cancer cell apoptosis through HDAC inhibition-enhanced oxidation therapy but also cooperatively induce immunogenic cell death and promote pro-inflammatory cytokine gene expression to reshape immunosuppressive microenvironment. Besides, nanodrugs can inhibit both primary and distant tumor growth effectively by elevating systemic anticancer immunity. This study provides a promising approach to synergize oxidation therapy with epigenetic modulation for safe and efficient breast cancer immunotherapy.
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高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Wubuli Abudukahaer,Chai Junwei,Liu Haoqiang,Nijat Dilaram,Li Jianmin,Xia Guoyu,Cao Qi,Zhang Saidan,Huang Weidong,Aipire Adila,Li Jinyao
Glycyrrhiza uralensis polysaccharides (GUPS) are widely applied in biomedicine and functional food due to their multiple pharmacological activities and low toxicity. Despite their widespread use, the in vivo metabolic profile of GUPS remains poorly understood. To address this gap, we developed a quantitative analysis method that involves labeling GUPS with visible fluorescein (5-DTAF) and near-infrared (NIR) fluorescein (Cy7), resulting in stable conjugates with substitution degrees of 0.81% for 5-DTAF and 0.39% for Cy7. The pharmacokinetic studies showed a biphasic elimination pattern in the blood concentration-time curve following both intravenous and oral administration, consistent with a two-compartment model. Using fluorescence quantification and NIR imaging, we observed that GUPS was distributed to various tissues, exhibiting higher concentrations particularly in liver, kidney and lung. Excretion studies indicated that feces were the major excretion pathway of GUPS after oral administration (60.98%), whereas urine was the main pathway after intravenous administration (31.16%). Notably, GUPS could be absorbed rapidly by gut (Tmax 1 ± 0.61 h) and showed a biological half-time t1/2 26.4 ± 7.72 h after oral administration. Furthermore, the Caco-2 cells uptake studies illustrated that macropinocytosis and clathrin-mediated endocytosis were participated in the transport of GUPS in intestine epithelium. This comprehensive analysis of the in vivo pharmacokinetics of GUPS not only enhances our understanding of its metabolic pathways but also establishes a foundational basis for its clinical application, optimizing its therapeutic potential and safety profile.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Rui Li,Wenhui Ruan,Rui Hao,Jue Chen,Chu Xu,Liyan Lu,Yingli Wang
Cannabidiol (CBD) is a natural cannabinoid with anti-epileptic, anti-inflammatory, and other biological activities. However, CBD is highly lipophilic, and its oral bioavailability is only 6%, which greatly limits its efficacy. Here, we aimed to overcome the poor solubility and low oral bioavailability of CBD by formulating O-carboxymethyl chitosan-grafted cholesterol succinate monoester-loaded cannabidiol nanomicelles (CBD/CCMC NMs). The particle size, polydispersity index, and zeta potential of the optimised CBD/CCMC NMs were 230.61 ± 1.82 nm, 0.17 ± 0.05, and -13.52 ± 1.24 mV, respectively. And it showed a spherical structure under scanning electron microscopy, exhibited stability at 25 °C and 37 °C, with pH-dependent release in vitro . There was improved the solubility of CBD in water by 568.67-fold and exhibited excellent biocompatibility. There was also improved bioavailability of CBD. Therefore, CBD/CCMC NMs can be used as delivery systems for improving the solubility and intestinal absorption of hydrophobic drugs.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-19
·
IF 10.6
Tang Bo,Wang Qiuxiang,Zhang Guowei,Zhang Aiwen,Zhu Lu,Zhao Rongrong,Gu Hongwei,Meng Jie,Zhang Junfang,Fang Guihua
Traditional eye drops are administered via topical instillation. However, frequent dosing is needed due to their relatively rapid precorneal removal and low ocular bioavailability. To address these issues, stearoyl L- carnitine-modified nanoemulsions (SC-NEs) were fabricated. The physicochemical properties of SC-NEs in terms of size, morphology, zeta potential, encapsulation efficiency, and in vitro drug release behavior were characterized. The cellular uptake and mechanisms of SC-NEs were comprehensively studied in human corneal epithelial cells and the stearoyl L- carnitine ratio in SC-NEs was optimized. The optimized SC-NEs could target the novel organic cation/carnitine transporter 2 (OCTN2) and amino acid transporter B (0 +) (ATB 0,+ ) on the corneal epithelium, which led to superior corneal permeation, ocular surface retention ability, ocular bioavailability. Furthermore, SC-NEs showed excellent in vivo anti-inflammatory efficacy in a rabbit model of endotoxin-induced uveitis. The ocular safety test indicated that the SC-NEs were biocompatible. In general, the current study demonstrated that OCTN2 and ATB 0,+ -targeted nanoemulsions were promising ophthalmologic drug delivery systems that can improve ocular drug bioavailability and boost the therapeutic effects of drugs for eye diseases. Graphical Abstract
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ACS Nano
·
2024
·
IF 15.8
Pengfei Yuan,Xiaodie Yan,Xiaoqing Zong,Xiaodi Li,Caiqi Yang,Xinjie Chen,Yuchao Li,Yaoqi Wen,Tianci Zhu,Wei Xue,Jian Dai
Cancer immunotherapy has emerged as a promising approach to cancer treatment in recent years. The physical and chemical properties of nanocarriers are critical factors that regulate the immune activation of antigen-presenting cells (APCs) in the tumor microenvironment (TME). Herein, we extensively investigated the behavior of liposome nanoparticles (Lipo-NPs) with different elasticities, focusing on their interaction with immune cells and their transport mechanisms from tumors to tumor-draining lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct elastic properties, their varied behaviors were observed, concerning immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell membranes, while those with medium elasticity facilitated the cargo delivery to macrophages through membrane fusion. Conversely, hard Lipo-NPs enter macrophages via classical cellular uptake pathways. Additionally, it was noted that softer Lipo-NPs displayed superior transport to tdLNs in vivo, attributed to their deformable nature with lower elasticity. As a result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating the STING pathway and enhancing transport to tdLNs, promoted abundant infiltration of tumor-infiltrating lymphocytes (TILs), leading to notable antitumor effects and extended survival in a melanoma mouse model. Furthermore, this study highlighted the potential synergistic effect of medium elasticity Lipo-NPs with immune checkpoint blockade (ICB) therapy in preventing tumor immune evasion. These findings hold promise for guiding immune-targeted delivery systems in cancer immunotherapy, particularly in vaccine design for tdLNs targeting and eradicating metastasis within tdLNs.
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