ABSTRACT
Poor cellular uptake and slow intracellular drug release remain the main barriers for the efficient application of micellar delivery system. Taking advantage of the overexpressed CD44 receptor and mild acidic microenvironment of tumour cells, CD44-targeted pH-responsive micelles based on the self-assembly of histidine-hyaluronic acid-dodecylamine (His-HA-DA) were prepared for the delivery of doxorubicin (DOX). These micelles exhibited pH-responsive behaviour with increased particle size, decreased encapsulation efficiency (EE%) of DOX and rapid release of DOX triggered by low pH. Compared with free DOX, DOX/HHD exhibited relatively high cellular uptake mainly via the CD44-mediated endocytosis. The on-demand intracellular release of DOX from DOX/HHD led to improved cytotoxicity. DOX/HHD also showed great penetration efficiency in 3D tumour spheres in vitro. Moreover, these micelles with suitable particle size gained excellent tumour-targeting effects, as well as improved anti-tumour effects and reduced side effects in vivo. In conclusion, these micelles with CD44 targeted and pH-responsive behaviours provide a promising strategy for the efficient delivery of anti-tumour drugs in vivo.
Subject(s)
Doxorubicin/chemistry , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Liberation , Hyaluronan Receptors/metabolism , Intracellular Space/metabolism , Cell Line, Tumor , Endocytosis , Humans , Hydrogen-Ion Concentration , Kinetics , MicellesABSTRACT
Flexible and lightweight photomultiplication-type organic photodetectors (PM-OPDs) have attracted wide attention for their broad application prospects, especially in the field of wearable electronic products. However, the commonly used indium tin oxide (ITO) conductive anode is not conducive to realize high-performance flexible PM-OPDs due to its rigidity and fragility. Here, on the flexible polyethylene terephthalate (PET) substrate, we successfully fabricate highly sensitive poly 3-hexylthiophene:phenyl-C70-butyric acid methyl ester (P3HT:PC70BM, 100:1) based PM-OPDs using ultra-thin silver films as transparent anodes. Specifically, a 1 nm thick MoO3 layer is utilized as the wetting layer for facilitating the silver film percolation, and a 2 nm thick MoO3 layer, as the hole transport layer, is coated on top of the ultra-thin silver film before coating the P3HT:PC70BM film. The as-prepared flexible PM-OPDs based on the ultra-thin silver film exhibit the optimal external quantum efficiency (EQE) and responsivity (R) of 1.3 × 105% and 388.4 A W-1, respectively, under -15 V bias, which are 1.98 times and 2.15 times greater than those of the ITO anode based device. More importantly, the device has good flexibility with the EQE maintaining 70.6% of its initial value after bending 10 times, and 51.4% of its initial value after bending 1000 times. This work paves the way for developing flexible PM-OPDs as well as other flexible optoelectronic devices.
