Ultrasound(US)activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release.However,the typical US frequency used for mechanochemistry is arou...Ultrasound(US)activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release.However,the typical US frequency used for mechanochemistry is around 20 kHz,producing inertial cavitation that exceeds the tolerance threshold of biological systems.Here,high-intensity focused US(HIFU)as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers(HBSPs)and microgels(MGLs).The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular cyclization.We reveal that HBSPs and MGLs effectively transduce HIFU as mechanical input to chemical output,demonstrated by the quantification of the release of fluorescent umbelliferone(UMB).Moreover,an in vitro study of drug release is carried out using camptothecin as the model drug,which is covalently loaded in MGLs,demonstrating the potential of our system for controlled drug delivery to cancer cells.展开更多
The development of ultrasound-responsive microcapsule structures has resulted in several spatiotemporally controlled drug delivery systems for macromolecular cargoes,including proteins,nucleic acids,and even cells for...The development of ultrasound-responsive microcapsule structures has resulted in several spatiotemporally controlled drug delivery systems for macromolecular cargoes,including proteins,nucleic acids,and even cells for biomedical applications.However,utilizing microcapsules to transport small molecular cargoes remains a challenge,because the leakage of drugs before ultrasound irradiation might cause side effects such as the undesired toxicity and the decrease of effective drug concentration at the target site.Herein,we present a novel strategy to tackle these shortcomings by employing nanodrugs which refers to nanoparticles coated with small molecule drugs.We showed that the drug leakage was prevented when encapsulating the nanodrug in microcapsules.Moreover,the fabricated drug delivery system was responsive not only to unfocused high-intensity ultrasound but also to the clinically relevant high-intensity focused ultrasound.Finally,as a proof of concept,we showed that the antibacterial activity of the nanodrug@Microcapsules could be activated by applying ultrasound in situ.These results may provide new insights into the development of ultrasound triggered small molecule drug delivery assisted by metallic nanoparticles.展开更多
基金supported by the German Research Foundation(grant nos.331065168,191948804,and 503981124)the National Natural Science Foundation of China(grant no.22277018)+2 种基金the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(grant no.LR23B030001)Wenzhou Institute,University of the Chinese Academy of Sciences(grant no.WIUCASQD2020015)M.X.acknowledges the financial support of the Alexander von Humboldt Foundation(grant no.3.5-CHN-1210658-HFST-P).
文摘Ultrasound(US)activation of mechanophores in polymers that initiates cascade chemical reactions is a promising strategy for on-demand molecule release.However,the typical US frequency used for mechanochemistry is around 20 kHz,producing inertial cavitation that exceeds the tolerance threshold of biological systems.Here,high-intensity focused US(HIFU)as a mechanical stimulus is introduced to drive the activation of disulfide mechanophores in hyperbranched star polymers(HBSPs)and microgels(MGLs).The mechanism of molecular release is attributed to the thiol-disulfide exchange reaction and subsequent intramolecular cyclization.We reveal that HBSPs and MGLs effectively transduce HIFU as mechanical input to chemical output,demonstrated by the quantification of the release of fluorescent umbelliferone(UMB).Moreover,an in vitro study of drug release is carried out using camptothecin as the model drug,which is covalently loaded in MGLs,demonstrating the potential of our system for controlled drug delivery to cancer cells.
基金the European Research Council through the Advanced Grant“Suprabiotics”(No.694610)J.L.F.was supported by a CSC scholarship.M.J.X.thanks the Alexander von Humboldt Foundation for a fellowship and financial support(No.3.5-CHN-1210658-HFST-P)L.F.Z.acknowledges financial support from Wenzhou Institute,University of Chinese Academy of Sciences(No.WIUCASQD2020015).
文摘The development of ultrasound-responsive microcapsule structures has resulted in several spatiotemporally controlled drug delivery systems for macromolecular cargoes,including proteins,nucleic acids,and even cells for biomedical applications.However,utilizing microcapsules to transport small molecular cargoes remains a challenge,because the leakage of drugs before ultrasound irradiation might cause side effects such as the undesired toxicity and the decrease of effective drug concentration at the target site.Herein,we present a novel strategy to tackle these shortcomings by employing nanodrugs which refers to nanoparticles coated with small molecule drugs.We showed that the drug leakage was prevented when encapsulating the nanodrug in microcapsules.Moreover,the fabricated drug delivery system was responsive not only to unfocused high-intensity ultrasound but also to the clinically relevant high-intensity focused ultrasound.Finally,as a proof of concept,we showed that the antibacterial activity of the nanodrug@Microcapsules could be activated by applying ultrasound in situ.These results may provide new insights into the development of ultrasound triggered small molecule drug delivery assisted by metallic nanoparticles.
