Breast cancer brain metastases(BCBMs)are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth.Chemotherapy and molecular targeted therapy are extremely ineffective for...Breast cancer brain metastases(BCBMs)are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth.Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable bloodbrain barrier(BBB).Accumulation studies prove that low density lipoprotein receptor-related protein 1(LRP1)is promising target for BBB transcytosis.However,as the primary clearance receptor for amyloid beta and tissue plasminogen activator,LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics.Matrix metalloproteinase-1(MMP1)is highly enriched in metastatic niche to promote growth of BCBMs.Herein,it is reported that nanoparticles(NPs-K-s-A)tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2(A),can surmount the BBB and escape LRP1-mediated clearance in metastatic niche.NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice,while comparable brain accumulation in normal mice.The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs.Due to the efficient BBB penetration,special and remarkable clearance escape,and facilitated therapeutic outcome,the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.展开更多
Since the first Palmaz-Schatz bare-metal stent （BMS） was implanted in human body in 1985, coronary stenting successfully resolved problem of the high restenosis rate in balloon dilatation era and soon became the pri...Since the first Palmaz-Schatz bare-metal stent （BMS） was implanted in human body in 1985, coronary stenting successfully resolved problem of the high restenosis rate in balloon dilatation era and soon became the primary means of clinical treatment of coronary artery disease. In order to meet the requirement of further reduction of the restenosis rate, drug-eluting stent （DES） was developed more than a decade later. With the excellent clinical efficacy, DESs established a milestone in the field of percutaneous coronary intervention （PCI）.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81703428 and 81973254)the Natural Science Foundation of Jiangsu Province(No.BK20191421,China)+1 种基金the Suzhou Science and Technology Development Project(No.SYS2019033,China)the Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD,China)。
文摘Breast cancer brain metastases(BCBMs)are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth.Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable bloodbrain barrier(BBB).Accumulation studies prove that low density lipoprotein receptor-related protein 1(LRP1)is promising target for BBB transcytosis.However,as the primary clearance receptor for amyloid beta and tissue plasminogen activator,LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics.Matrix metalloproteinase-1(MMP1)is highly enriched in metastatic niche to promote growth of BCBMs.Herein,it is reported that nanoparticles(NPs-K-s-A)tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2(A),can surmount the BBB and escape LRP1-mediated clearance in metastatic niche.NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice,while comparable brain accumulation in normal mice.The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs.Due to the efficient BBB penetration,special and remarkable clearance escape,and facilitated therapeutic outcome,the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.
文摘Since the first Palmaz-Schatz bare-metal stent （BMS） was implanted in human body in 1985, coronary stenting successfully resolved problem of the high restenosis rate in balloon dilatation era and soon became the primary means of clinical treatment of coronary artery disease. In order to meet the requirement of further reduction of the restenosis rate, drug-eluting stent （DES） was developed more than a decade later. With the excellent clinical efficacy, DESs established a milestone in the field of percutaneous coronary intervention （PCI）.
