Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescen...Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescent biosensor(α-Fuc-DCM)was elaborately designed and synthesized for rapid and ratiometric detection of AFU activity in cells and HCC tumor mouse models.In the presence of AFU,this biosensor shows an enhancement in NIR emission in a ratiometric manner,which significantly improves the detection accuracy with the limit of detection as low as 4.8 mU/mL.Taking advantage of these merits,the activity of AFU in lysosomes could be visualized using ratiometric and NIR dual modality in living cells.Furthermore,its remarkable application for monitoring of endogenous AFU activity in HCC tumor-bearing mouse model is also demonstrated with bright fluorescence signal,which indicated that the biosensor could clearly monitor the liver tumor in the early stage.Importantly,the α-Fuc-DCM probe can be utilized to detect the AFU in serum from HCC patients.This strategy offers a promising biosensor system for early diagnosis of HCC and studying the roles of AFU in cancers.展开更多
Doxorubicin(DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for...Doxorubicin(DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for controlled drug release and site-specific treatment. The core region consisted of poly(lactic co-glycolic acid) and poly-caprolactone, whereas the shell region was composed of cross-linked gelatin.DOX was enclosed in the core region of a core-shell nanofiber obtained by electrospinning. This implantable delivery device was implanted on the top of the melanoma in a mouse model, which had shown a DOX-controlled release profile with sustained and sufficient local concentration against melanoma growth in mice with negligible side effects. Compared with the traditional intravenous administration,the implantable device allows precisely localized treatment and therefore can reduce the dose, decrease the injection frequency, and ensure antitumor efficacy associated with lower side effects to normal tissues. Using a coaxial electrospinning process, it is promising to deliver different hydrophobic or hydrophilic drugs for direct tumor site-specific therapy without large systemic doses and minimized systemic toxicity.展开更多
基金National Key R&D Program of China,Grant/Award Number:2017YFE0132200National Natural Science Foundation of China,Grant/Award Numbers:5191160730,51873092,81921004,81802116+3 种基金Natural Science Foundation of Guangdong Province,Grant/Award Number:2021A1515011633Science and Technology Program of Guangzhou,Grant/Award Number:202102020705Outstanding Youths Development Scheme of Nanfang Hospital,Southern Medical University,Grant/Award Number:2018J002Tianjin Science Fund for Distinguished Young Scholars,Grant/Award Number:19JCQJC61200。
文摘Detection and imaging of α-L-fucosidase(AFU)is of great value to understand its roles in hepatocellular carcinoma(HCC)and tumor early diagnosis,but ideal assays are still lacking.Herein,a near-infrared(NIR)fluorescent biosensor(α-Fuc-DCM)was elaborately designed and synthesized for rapid and ratiometric detection of AFU activity in cells and HCC tumor mouse models.In the presence of AFU,this biosensor shows an enhancement in NIR emission in a ratiometric manner,which significantly improves the detection accuracy with the limit of detection as low as 4.8 mU/mL.Taking advantage of these merits,the activity of AFU in lysosomes could be visualized using ratiometric and NIR dual modality in living cells.Furthermore,its remarkable application for monitoring of endogenous AFU activity in HCC tumor-bearing mouse model is also demonstrated with bright fluorescence signal,which indicated that the biosensor could clearly monitor the liver tumor in the early stage.Importantly,the α-Fuc-DCM probe can be utilized to detect the AFU in serum from HCC patients.This strategy offers a promising biosensor system for early diagnosis of HCC and studying the roles of AFU in cancers.
基金supported by the Project Electro Med (11115313) from the Danish Council for Strategic Researchthe National Science Fund for Excellent Young Scholars (31622026)+3 种基金the National Natural Science Foundation of China (U1532122, 21320102003, 21471044)the National Key Research and Development Plan (2016YFA0201600, 2016YFA0203204)the National Science Fund for Distinguished Young Scholars (11425520)Youth Innovation Promotion Association of the Chinese Academy of Sciences (2014031)
文摘Doxorubicin(DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for controlled drug release and site-specific treatment. The core region consisted of poly(lactic co-glycolic acid) and poly-caprolactone, whereas the shell region was composed of cross-linked gelatin.DOX was enclosed in the core region of a core-shell nanofiber obtained by electrospinning. This implantable delivery device was implanted on the top of the melanoma in a mouse model, which had shown a DOX-controlled release profile with sustained and sufficient local concentration against melanoma growth in mice with negligible side effects. Compared with the traditional intravenous administration,the implantable device allows precisely localized treatment and therefore can reduce the dose, decrease the injection frequency, and ensure antitumor efficacy associated with lower side effects to normal tissues. Using a coaxial electrospinning process, it is promising to deliver different hydrophobic or hydrophilic drugs for direct tumor site-specific therapy without large systemic doses and minimized systemic toxicity.
