JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Fei Wang,Xuyang Li,Xialin Hu,Wenya Zhuang,Jiewei Lai,Wenchao Wang,Xuanrong Sun,Hong Wang,Qingyong Li
FLQY2 is a camptothecin derivative modified by FL118 and proved to be good antitumor activity in vitro . However, its poor solubility leads to the low therapeutic efficacy in vivo . Here, the injectable FLQY2 lyophilized powder was prepared with Kolliphor® HS 15 (HS 15), which was called HS 15-FLQY2. The preparation process of HS 15-FLQY2 was optimized by orthogonal design and the lyophilization process was investigated by single factor experiment. Moreover, the formulation was characterized, the pharmacokinetics study and the antitumor activity were carried out in vivo . As the results, HS 15-FLQY2 (1:1500, w/w) containing 5% mannitol as cryoprotectant showed good appearance and 70% entrapment efficiency. HS 15-FLQY2 revealed low particle size (<16 nm), better homogeneity (PDI <0.2) and remained stable for 24 h in water. In addition, the data of the DSC , XRD and FTIR demonstrated that FLQY2 was distributed within micelles . In vivo , the bioavailability of HS 15-FLQY2 (i.p.) was improved significantly compared with oral CD-FLQY2 (a cyclodextrin inclusion complex of FLQY2). In addition, HS 15-FLQY2 demonstrated higher tumor inhibition effect than capecitabine , confirming the possibility of treatment cancer by the delivery of FLQY2.
研究领域:
药剂学
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肿瘤学
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生物化学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2026
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IF 7.8
Xin Zhang,Zutong Cui,Wenming Liang,Zihan Zhang,Jianming Sun,Liming Gao,Ming Shi,Zhiwei Liu,Kun Li,Jian Li
Phototherapy not only targets tumor cells for destruction but also triggers immunogenic cell death (ICD), thereby activating systemic immunity. Traditional photothermal therapy (PTT), however, damages adjacent normal tissues, and photodynamic therapy (PDT) creates severe hypoxia within tumor tissues, which promotes immune evasion and reduces the effectiveness of immunotherapy. In this study, we developed a biomimetic nanomodulators-cell membrane-coated gambogic acid/indocyanine green micelles loaded with HIF-1α siRNA (CM-IGM/siRNA) to achieve mild photothermal therapy (mPTT), enhance photodynamic therapy (PDT), and modulate the tumor microenvironment (TME). This platform utilizes gambogic acid (GA) to inhibit HSP90 expression and synergizes with HIF-1α siRNA to suppress HIF-1α expression, thereby ameliorating hypoxic and immunosuppressive TME. HSP90 inhibition further reduces tumor cell thermotolerance, enabling effective tumor cell ablation at mild hyperthermia temperatures (42−45 °C) characteristic of mPTT. Furthermore, we found that π–π stacking of GA with indocyanine green (ICG) enhances ICG photostability and boosts reactive oxygen species (ROS) generation. The elevated ROS production significantly improves PDT efficacy and, in combination with mPTT, potentiates the ICD of tumor cells. Overall, this strategy offers a significant advancement in cancer immunotherapy by improving the tumor microenvironment and enhancing immune activation.
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Chenglong Li,Shuhao Xu,Xin Li,Huaiyu Su,Can Qian,Yingying Hou,Sanjun Shi
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, damage, and disability. Activated fibroblast-like synoviocytes (FLSs), abundant in RA synovium, crucially facilitate disease progression. These activated FLSs drive RA pathogenesis by upregulating adhesion molecules, proinflammatory cytokines, chemokines, and major histocompatibility complex class II (MHC-II). This upregulation facilitates their interaction with CD4 + T cells, triggering an inflammatory cascade that exacerbates synovial inflammation. To address this, a DSPE-mPEG 2000 -GPA-KLVFF-decorated liposome loaded with dexamethasone (DPGK@Lipo-Dex) is developed to precisely target FLSs in arthritic joints. DPGK@Lipo-Dex achieves efficient binding to FLSs through a specific enzymatic interaction between fibroblast activation protein-α (FAP-α) and GPA, along with prolonged retention in the joints due to the fibrillar transformation of KLVFF. In vitro studies demonstrate that DPGK@Lipo-Dex enhances cellular uptake and reduces MHC-II expression on aggressive FLSs. In adjuvant-induced arthritis (AIA) rats, DPGK@Lipo shows specific distribution patterns that target both inflamed joints and FLSs. Treatment with DPGK@Lipo-Dex leads to a downregulation of MHC-II expression, a decrease in the number of activated T cells within the synovium, and a reduction in levels of proinflammatory mediators. Overall, DPGK@Lipo-Dex effectively suppresses FLSs-related responses and ultimately results in inflammatory remission. This makes DPGK@Lipo-Dex a promising candidate for nano-therapeutic treatment in rheumatoid arthritis.
研究领域:
免疫学
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纳米医学
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风湿病学
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分子靶向治疗
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药剂学
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转化医学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2021
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IF 9.381
Jingwen Luo,Zhiwei Zhang,Yingchun Zeng,Yanming Dong,Lixin Ma
Components of the extracellular matrix (ECM) are overexpressed in fibrotic liver. Collagen is the main component of the liver fibrosis stroma. Here we demonstrate that chondroitin sulfate coated multilayered 50-nm nanoparticles encapsulating collagenase and silibinin (COL + SLB-MLPs) break down the dense collagen stroma, while silibinin inhibits activated hepatic stellate cells. The nanoparticles were taken up to a much greater extent by hepatic stellate cells than by normal hepatocytes, and they down-regulated production of type I collagen. In addition, chondroitin sulfate protected the collagenase from premature deactivation. COL + SLB-MLPs were delivered to the cirrhotic liver, and the collagenase and silibinin synergistically inhibited fibrosis in mice. Immunofluorescence staining of liver tissues revealed that CD44, mediated by chondroitin sulfate, delivered the nanoparticles to hepatic stellate cells. This strategy holds promise for degrading extracellular stroma and thereby facilitating drug penetration into fibrotic liver and related diseases such as liver cirrhosis and liver cancer.
研究领域:
药学
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生物医学工程
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肝脏疾病研究
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Jun Li,Yangyang Yang,Xiumin Han,Jing Li,Mengxiao Tian,Wenjing Qi,Huniu An,Chuanchuan Wu,Yao Zhang,Shuai Han,Liping Duan,Weisi Wang,Wenbao Zhang
Background Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment.Methods Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE.Results H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals.Conclusion Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.
研究领域:
药理学
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寄生虫学
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纳米技术
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医学
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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）