ABSTRACT
Human heavy chain ferritin (HFn) protein cage has been explored as a nanocarrier for targeted anticancer drug delivery. Here, we introduced a matrix metalloproteinases (MMPs)-cleavable sequence into the DE loop of HFn, creating an MMP-responsive variant, MR-HFn, for localized and extracellular drug release. The crystal structure of MR-HFn revealed that the addition of the MMPs recognition sequence did not affect the self-assembly of HFn but presented a surface-exposed loop susceptible to MMPs cleavage. Biochemical analysis indicated that this engineered protein cage is responsive to MMPs, enabling the targeted release of encapsulated drugs. To evaluate the therapeutic potential of this engineered protein cage, monosubstituted ß-carboxy phthalocyanine zinc (CPZ), a type of photosensitizer, was loaded inside this protein cage. The prepared CPZ@MR-HFn showed higher uptake and stronger phototoxicity in MMPs overexpressed tumor cells, as well as enhanced penetration into multicellular tumor spheroids compared with its counterpart CPZ@HFn in vitro. In vivo, CPZ@MR-HFn displayed a higher tumor inhibitory rate than CPZ@HFn under illumination. These results indicated that MR-HFn is a promising nanocarrier for anticancer drug delivery and the MMP-responsive strategy here can also be adapted for other stimuli.
Subject(s)
Antineoplastic Agents , Drug Liberation , Matrix Metalloproteinases , Protein Engineering , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Matrix Metalloproteinases/metabolism , Animals , Cell Line, Tumor , Mice , Ferritins/chemistry , Ferritins/metabolism , Indoles/chemistry , Indoles/pharmacology , Drug Carriers/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistryABSTRACT
A polarization-independent liquid crystal lens that is based on axially symmetric photoalignment is demonstrated. This liquid crystal lens is fabricated by combining radially and azimuthally aligned liquid crystal films with gradient alignments. The configurations of liquid crystals on the substrates are confirmed both optically and using a scanning electron microscope. The focal length of the polarization-independent liquid crystal lens can be controlled by applying various voltages. The device is simple to fabricate, and very convenient to use. It therefore has great practical potential.
Subject(s)
Lenses , Liquid Crystals/chemistry , Refractometry/instrumentation , Computer-Aided Design , Equipment Design , Equipment Failure AnalysisABSTRACT
This investigation demonstrates a simple but accurate method for measuring the helical twisting power of chiral doped liquid crystals using axially symmetrical photo-alignment in azo dye-doped liquid crystal films. As reported in our previous paper, a reversed twist effect produces a disclination line in photo-aligned axially symmetrical liquid crystal films. The pitch and helical twisting power can be obtained by measuring the rotation angle of the disclination line in chrial doped liquid crystal. This method is independent of cell gap and provide an error below 0.5%.
ABSTRACT
[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.
