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
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.
