Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we...Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.展开更多
Tumor sentinel lymph node(SLN)metastasis plays a vital role in tumor staging and therapeutic decision-making process.However,precise diagnosis of primary tumors and lymphatic metastases is still hindered by low imagin...Tumor sentinel lymph node(SLN)metastasis plays a vital role in tumor staging and therapeutic decision-making process.However,precise diagnosis of primary tumors and lymphatic metastases is still hindered by low imaging resolution and poor photostability of fluorescent probes.Herein,we report three novel IR820-fatty acid(FA)conjugates(IR-OA,IR-LA,and IR-PA)for precise lymphatic metastasis illumination and primary tumor diagnosis.The IR-FA conjugates are able to non-covalently bound to albumin in vivo,and the fluorescence quantum yield is significantly enhanced after incubation with bovine serum albumin(BSA)in vitro.Moreover,the BSA-IR-FA conjugates display large Stokes shift(>120 nm),dramatically improving in vivo imaging resolution.Among them,IR-PA demonstrates distinct advantage over IR-OA,IR-LA,and IR-maleimide(MAL)(fluorescent probe previously reported by our group)in terms of fluorescence quantum yield,photostability,and imaging resolution.As a result,IR-PA exhibits satisfactory imaging results with high fluorescence intensity and imaging resolution in sentinel lymph node metastasis illumination and primary tumor location.Our findings provide a self-adaptive albumin-binding near-infrared probe conjugate for accurate diagnosis of primary tumors and lymphatic metastases.展开更多
基金the National Key Research and Development Program of China(No.2021YFA0909900)the National Natural Science Foundation of China(Nos.82073777 and 81803442)+1 种基金the General Project of Liaoning Provincial Department of Education(Nos.LJKZ0927 and LJKQZ2021034)the Natural Science Foundation of Liaoning Province(No.2022-BS-157).
文摘Despite great therapeutic effect of Abraxane®,complex preparation technology and unfavorable pharmacokinetics still restricted the clinical application of albumin-based paclitaxel(PTX)nanoparticles(NPs).Herein,we reported that an albumin-binding prodrug,phenylboronic acid-conjugated PTX(P-PTX),can form the uniform NPs with the diameters around 100 nm with the help of albumin via simple one-step nano-precipitation method.The albumin-based nanomedicines were stabilized by the integration of a single boronic acid with PTX due to the increased affinity based on multiple intermolecular interactions.We found that albumin-based P-PTX NPs exhibited superior colloidal stability over albumin-based PTX NPs through one-step nanoprecipitation approach,achieving longer in vivo circulation time and higher concentration in tumor than those of the marketed Abraxane®.Furthermore,the albumin-based P-PTX NPs with great stability and enhanced intratumoral enrichment,increased the maximum tolerated dose of PTX,remarkably suppressed the growth of breast tumor and lung metastasis,prolonged survival of melanoma tumors-bearing mice.Such a convenient and effective system gains an insight into the impact of phenylboronic acid group on the albumin-based PTX NPs,provides potent strategy for the rational design of albumin-based antitumor nanomedicines.
基金supported by the Liaoning Revitalization Talents Program(No.XLYC1907129)the Excellent Youth Science Foundation of Liaoning Province(No.2020-YQ-06)the China Postdoctoral Science Foundation(No.2020M670794).
文摘Tumor sentinel lymph node(SLN)metastasis plays a vital role in tumor staging and therapeutic decision-making process.However,precise diagnosis of primary tumors and lymphatic metastases is still hindered by low imaging resolution and poor photostability of fluorescent probes.Herein,we report three novel IR820-fatty acid(FA)conjugates(IR-OA,IR-LA,and IR-PA)for precise lymphatic metastasis illumination and primary tumor diagnosis.The IR-FA conjugates are able to non-covalently bound to albumin in vivo,and the fluorescence quantum yield is significantly enhanced after incubation with bovine serum albumin(BSA)in vitro.Moreover,the BSA-IR-FA conjugates display large Stokes shift(>120 nm),dramatically improving in vivo imaging resolution.Among them,IR-PA demonstrates distinct advantage over IR-OA,IR-LA,and IR-maleimide(MAL)(fluorescent probe previously reported by our group)in terms of fluorescence quantum yield,photostability,and imaging resolution.As a result,IR-PA exhibits satisfactory imaging results with high fluorescence intensity and imaging resolution in sentinel lymph node metastasis illumination and primary tumor location.Our findings provide a self-adaptive albumin-binding near-infrared probe conjugate for accurate diagnosis of primary tumors and lymphatic metastases.
