Abstract
BackgroundCancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy.MethodsThe morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro.ResultsSP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy.ConclusionAll the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications.Graphical
Highlights
Cancer is the most serious world’s health problems on the global level and various strategies have been developed for cancer therapy
Scheme 1. a Chemical structures of amino group modified pillar[5]arene (AP5), ferrocene dicarbaldehyde (FeE), and target molecule FA-Py. b The illustration of preparation and modification of pillar[5]arene-based supramolecular therapeutic nano-platform. c The targeted synergistic chemo-chemodynamic cancer therapy of the multifunctional FA-Py/SP/glucose oxidase (GOx)/Doxorubicin hydrochloride (Dox) NPs of pillar[5]arene endow SP/GOx NPs with excellent host– guest properties, so target molecules (FA-Py) can be introduced on its surface. In this case, when the resultant pillar[5]arene-based FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently
With amino group modified pillar[5]arene (AP5) in hands, supramolecular polymeric nanoparticles with (SP/GOx NPs) or without (SP NPs) GOx were constructed in DMSO at 80 ̊C overnight by employing AP5 and ferrocene dicarbaldehyde (FeE) as building blocks
Summary
Cancer is the most serious world’s health problems on the global level and various strategies have been developed for cancer therapy. Different functional groups, such as target units, fluorescent groups and pro-drugs, can be modified into systems by dynamic and reversible supramolecular interactions [5]. Due to the differences in environments between the normal and tumor tissues, the release of the loaded drug-molecules can be precisely achieved [6]. Macrocylics, such as cyclodextrins, calixarenes and pillararenes, are the ideal platforms for construction of chemotherapeutic platforms through supramolecular interactions due to they contained sizecontrollable cavities where guests can be penetrated [7, 8]
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