Abnormal tumor microenvironment imposes barriers to tumor penetration of nanomedicine,which remains a major challenge for effective anti-tumor.Herein,we present disulfide-based nanoparticles that actively penetrate de...Abnormal tumor microenvironment imposes barriers to tumor penetration of nanomedicine,which remains a major challenge for effective anti-tumor.Herein,we present disulfide-based nanoparticles that actively penetrate deep tumors in vivo through a thiol-mediated transportation pathway.To achieve active tumor accumulation in vivo,disulfide-based nanoparticles are modified with folic acid units(FA-DBNPs).It is gratifying that FA-DBNPs still enter cells via the thiol-mediated pathway,which facilitates transcellular transportation and tumor penetration both in vitro and in vivo.Besides,FA-DBNPs exhibit GSH concentration-dependent depolymerization characterization,indicating that the GSH level in tumor tissues regulates the penetration depth of FA-DBNPs.Benefiting from these advantages,FA-DBNPs showed potent anti-tumor activity in mouse models,leading to the significant regression of tumors.The current study lays a foundation that thiol-mediated transportation is a promising approach in nanomedicine design for solid tumor therapy.展开更多
Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces pati...Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.展开更多
基金supported by the National Key R&D Program of China(2020YFA0210800)the National Natural Science Foundation of China(21974022,22027805)the Major Project of Science and Technology of Fujian Province(2020HZ06006)。
文摘Abnormal tumor microenvironment imposes barriers to tumor penetration of nanomedicine,which remains a major challenge for effective anti-tumor.Herein,we present disulfide-based nanoparticles that actively penetrate deep tumors in vivo through a thiol-mediated transportation pathway.To achieve active tumor accumulation in vivo,disulfide-based nanoparticles are modified with folic acid units(FA-DBNPs).It is gratifying that FA-DBNPs still enter cells via the thiol-mediated pathway,which facilitates transcellular transportation and tumor penetration both in vitro and in vivo.Besides,FA-DBNPs exhibit GSH concentration-dependent depolymerization characterization,indicating that the GSH level in tumor tissues regulates the penetration depth of FA-DBNPs.Benefiting from these advantages,FA-DBNPs showed potent anti-tumor activity in mouse models,leading to the significant regression of tumors.The current study lays a foundation that thiol-mediated transportation is a promising approach in nanomedicine design for solid tumor therapy.
基金supported by the National Natural Science Foundation of China(Nos.22304027 and 81570807)the Natural Science Foundation of Fujian Province(No.2022J01208)+2 种基金the Joint Funds for the Innovation of Science and Technology,Fujian Province(Nos.2024Y9109,2024Y9107,and 2024Y9103)the Startup Fund for Scientific Research,Fujian Medical University(No.XRCZX2021015)the Scientific Research Foundation of State Key Laboratory of Vaccines for Infectious Diseases,and Xiang An Biomedicine Laboratory(No.2023XAKJ0101018).
文摘Intraocular injection of anti-vascular endothelial growth factor(VEGF)antibodies is the first-line treatment for ocular neovascular diseases.However,the invasive nature of this administration method often reduces patient compliance and negatively affects treatment outcomes.Noninvasive formulations of anti-VEGF antibody are urgently needed,but their development remains challenging due to the complex ocular barriers.This study identified an anti-VEGF singledomain antibody(sdVE01)that is three times smaller than the commercially available ranibizumab,yet retains a comparable anti-angiogenic effect to the heavy-chain region of ranibizumab(VHHL).Additionally,four dithiolane molecules(DM)were designed to construct DM-based antibody nanoformulations,which effectively penetrate both the anterior and posterior segments of the eye.Upon eyedrop administration,DM-based antibody nanoformulations significantly inhibited the VEGF pathway and reduced neovascularization in a corneal alkali-burn rat model.Notably,the therapeutic effects of the antibody eyedrops were comparable to those of ranibizumab administered via subconjunctival injection.Overall,the dithiolane-based antibody eyedrops represent a promising noninvasive strategy for treating ocular neovascularization diseases.
