Modification of contact lenses via metal-organic frameworks for glaucoma treatment

The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure.Here,human contact lenses are modified with highly porous metal-organic frameworks with sustained release of brimonidine for prolonged glaucoma treatment.Various metal-organic frameworks were screened for their attachment to lenses,loading with brimonidine,and drug-release properties.Opti-mized therapeutic ocular lenses conjugated with MIL-101(Cr)frameworks maintain optical transparency and power.Coating of lenses with MIL-101(Cr)nanoparticles reduced brimonidine washout with tears and ensured a gradual and localized release of the drug into the eyeball through the cornea.The hybrid lenses provided a 4.5-fold better decrease in eye pressure,compared by area under the curve(AUC)value to a commercially available brimonidine tartrate solution.Therapeutic lenses did not induce any notable eye irritation or corneal damage in vivo.The newly devel-oped hybrid lenses are expected to provide a robust platform for the therapy and prevention of various ocular diseases.

Genetically encoded BRET-activated photodynamic therapy for the treatment of deep-seated tumors

Photodynamic therapy(PDT)is one of the most appealing photonic modalities for cancer treatment based on anticancer activity of light-induced photosensitizer-mediated reactive oxygen species(ROS),but a limited depth of light penetration into tissues does not make possible the treatment of deep-seated neoplasms and thus complicates its widespread clinical adoption.Here,we introduce the concept of genetically encoded bioluminescence resonance energy transfer(BRET)-activated PDT,which combines an internal light source and a photosensitizer(PS)in a single-genetic construct,which can be delivered to tumors seated at virtually unlimited depth and then triggered by the injection of a substrate to initiate their treatment.To illustrate the concept,we engineered genetic NanoLuc-miniSOG BRET pair,combining NanoLuc luciferase flashlight and phototoxic flavoprotein miniSOG,which generates ROS under luciferase-substrate injection.We prove the concept feasibility in mice bearing NanoLuc-miniSOG expressing tumor,followed by its elimination under the luciferase-substrate administration.Then,we demonstrate a targeted delivery of NanoLuc-miniSOG gene,via tumor-specific lentiviral particles,into a tumor,followed by its successful elimination,with tumor-growth inhibition(TGI)coefficient exceeding 67%,which confirms a great therapeutic potential of the proposed concept.In conclusion,this study provides proof-of-concept for deep-tissue“photodynamic”therapy without external light source that can be considered as an alternative for traditional PDT.

Resolution and contrast enhancement of laser-scanning multiphoton microscopy using thulium-doped upconversion nanoparticles

High-contrast optical imagi ng is achievable using phosphoresce nt labels to suppress the short-lived background due to the optical backscatterand autofluoresce nee.However,the long-lived phosphorescence is generally incompatible with high-speed laser-scan ning imaging modalities.Here,we show that upc on versi on nan oparticles of structure NaYF4:Yb co-doped with 8%Tm(8T-UCNP)in combi nation with a commerciallaser-scanning multiphoton microscopy are uniquely suited for labeling biological systems to acquire high-resolution images with the enhancedcon trast.In comparison with many phosphoresce nt labels,the 8T-UCNP emission lifetime of-15μs affords rapid image acquisition.Thehigh-order optical nonlinearity of the 8T-UCNP(n=4,as confirmed experimentally and theoretically)afforded pushing the resolution limitattain able with UCNPs to the diffraction-limit.The contrast enha nceme nt was achieved by suppressing the backgro und using(i)ban dpassspectral filtering of the narrow emission peak of 8T-UCNP at 455-nm,and(ii)time-gating implemented with a time-correlated single-photon counting system that demonstrated the contrast enhancement of>2.5-fold of polyethyle neimine-coated 8T-UCNPs take n up by huma nbreast adeno carcinoma cells SK-BR-3.As a result,discrete 8T-UCNP nan oparticles became clearly observable in the freshly excised splee ntissue of laboratory mice 15-min post in trave nous injectio n of an 8T-UCNP solution.The dem on strated approach paves the way forhigh-contrast,high-resoluti on,and high-speed multiphot on microscopy in challe nging envir onments of i ntense autofluorescence,exogenous staining,and turbidity,as typically occur in intravital imaging.