Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for ...Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for modification with payload,but the relatively low molecular weight of this construction simultaneously results in short half-life time which hinders its application in cancer therapy.In this work,we prepared a nanomedicine self-assembled from the conjugate of affibody(ZPDGFRβ:09591,PDGFRβ:platelet-derived growth factor receptorβ)with monomethyl auristatin E(MMAE)through cathepsin B cleavable dipeptide linker for targeted colorectal cancer therapy.The nanoscale characteristics of ZPDGFRβ:09591-MMAE affibody-drug conjugate nanomedicine(ZPDGFRβ:09591-M ADCN)resulted in enhanced pharmacokinetics,improved drug accumulation,and promoted biosecurity performance than those of free drugs.As a result,ZPDGFRβ:09591-M ADCN exhibited excellent antitumor efficacy with tumor inhibition rates(TIR)over 99.0%in PDGFRβ-positive tumor models with small solid tumors(~150 mm^(3))or large established tumors(~500 mm^(3)),indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.展开更多
Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC)...Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.展开更多
基金supported by the National Key Research and Development Plan of China(No.2020YFA0907702)the National Facility for Translational Medicine(Shanghai)(No.TMST-2020-001).
文摘Affibody is a new class of small non-immunoglobulin affinity proteins that possesses high affinity at the picomole level to several tumor overexpressed receptors.Owing to the simple framework,affibody is flexible for modification with payload,but the relatively low molecular weight of this construction simultaneously results in short half-life time which hinders its application in cancer therapy.In this work,we prepared a nanomedicine self-assembled from the conjugate of affibody(ZPDGFRβ:09591,PDGFRβ:platelet-derived growth factor receptorβ)with monomethyl auristatin E(MMAE)through cathepsin B cleavable dipeptide linker for targeted colorectal cancer therapy.The nanoscale characteristics of ZPDGFRβ:09591-MMAE affibody-drug conjugate nanomedicine(ZPDGFRβ:09591-M ADCN)resulted in enhanced pharmacokinetics,improved drug accumulation,and promoted biosecurity performance than those of free drugs.As a result,ZPDGFRβ:09591-M ADCN exhibited excellent antitumor efficacy with tumor inhibition rates(TIR)over 99.0%in PDGFRβ-positive tumor models with small solid tumors(~150 mm^(3))or large established tumors(~500 mm^(3)),indicating that ZPDGFRβ:09591-MMAE ADCN is promising for the clinic application in colorectal cancer therapy.
基金supported by the National Natural Science Foundation of China(81421004,81301268)Beijing Nova Program Interdisciplinary Cooperation Project (xxjc201812)+2 种基金International S&T Cooperation Program of China(2015DFA30440)Beijing Nova Program(Z131107000413063)CAMS Innovation Fund for Medical Sciences(CIFMS 2020-I2M-C&T-B-035)。
文摘Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.
