Search

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8. GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti- VEGF Fab and similar suppression of VEGF-induced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE., Introduction Leber congenital amaurosis (LCA) is a group of diseases in which severe visual disability starts early in life. In a subgroup of patients with LCA due to a mutation [...]

Amphiphilic trismethylpyridylporphyrin-C70 (PC70) dyad with improved photosensitization has been successfully prepared. The PC70 dyad forms a liposomal nanostructure through molecular self-assembling. An increased absorption coefficient in the visible region, good biocompatibility, and high photostability were observed on the self-assembling structure. Surprisingly, in comparison with previously reported photosensitizer porphyrins, PC70 exhibited an enhanced photodynamic therapy (PDT) effect under hypoxia conditions. Further investigations illustrated that PC70 went through an extremely long-life triplet state (211.3 μs) under hypoxia, which enabled the exiguous oxygen to approach and interact with the activated (3P-C70)* more efficiently and produce more singlet oxygen. This would overcome the problem of existing photosensitizers of low PDT efficiency in cancerous tissues under hypoxia. The excellent properties of PC70 dyad make it a promising phototherapeutic agent, especially for the treatment of early- and late-stage cancers under shallow and hypoxia tissues. [ABSTRACT FROM AUTHOR]

Smart pH-responsive polymeric micelles have attractedmuch attentionas one of the most promising drug delivery candidates. In this paper,a different substitution of deoxycholic acid (DCA) and folic acid(FA) comodified hydroxypropyl chitosans (HPCHS) were synthesized fordoxorubicin (DOX) targeted delivery and controllable release. Theresults indicate that the DOX-release behavior is pH-responsive andclosely related with the grafting proportions of the two hydrophobicingredients. The pH-responsive mechanism for the optimized (6%DCA)-HPCHS-(0.1%FA)was suggested, resulting from a synergistic effect of gradual hydrolysisof the amido bond and electrostatic repulsion between the subsequentlyprotonated DOX and the amino residue of the chitosan backbone undera cancerous microenvironment. Moreover, the DOX/(6%DCA)-HPCHS-(0.1%FA)micelle as a promising targeted drug delivery system in cancer therapywas evaluated by cell growth inhibition assays and confocal lasermicroscopy in vitro. The results clearly demonstrate a controlledrelease of its cargo and promoted curative efficacy of DOX. [ABSTRACT FROM AUTHOR]

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8.GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti-VEGF Fab and similar suppression of VEGF-induced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE. [ABSTRACT FROM AUTHOR]

Abstract: C60-carboxyfullerene, C60[C(COOH)2]2, has been proven to function as peroxidase mimetics that can catalyze the reaction of peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to produce a blue color reaction. Kinetic studies further indicate that C60[C(COOH)2]2 has an even higher affinity to TMB than that of the natural enzyme, horseradish peroxidase (HRP). C60[C(COOH)2]2/glucose oxidase (GO x )/TMB system provides a novel colorimetric sensor for glucose and shows good response toward glucose detection over a range of 1.0–40μM with a limit of detection 0.5μM (3σ/slope). Moreover, this sensitive and selective sensor can be successfully applied for the quantitative determination of glucose in human serum. The results indicate that it is a simple, cheap, convenient, highly selective, sensitive, and easy handling colorimetric assay. [Copyright &y& Elsevier]

Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo. We endowed tetra(piperazino)fullerene epoxide (TPFE)-based nanoparticles with non-adhesive surface polyethylene glycol (PEG) coatings, thereby enabling the nanoparticles to cross the airway mucus gel layer and avoid phagocytic uptake by alveolar macrophages. In parallel, we utilized a hypotonic vehicle to facilitate endocytic uptake of the PEGylated nanoparticles by lung parenchymal cells via the osmotically driven regulatory volume decrease (RVD) mechanism. We demonstrate that this two-pronged delivery strategy provides safe, wide-spread and high-level transgene expression in the lungs of both healthy mice and mice with chronic lung diseases characterized by reinforced delivery barriers., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Amphiphilic trismethylpyridylporphyrin-C 70 (PC 70 ) dyad with improved photosensitization has been successfully prepared. The PC 70 dyad forms a liposomal nanostructure through molecular self-assembling. An increased absorption coefficient in the visible region, good biocompatibility, and high photostability were observed on the self-assembling structure. Surprisingly, in comparison with previously reported photosensitizer porphyrins, PC 70 exhibited an enhanced photodynamic therapy (PDT) effect under hypoxia conditions. Further investigations illustrated that PC 70 went through an extremely long-life triplet state (211.3 μs) under hypoxia, which enabled the exiguous oxygen to approach and interact with the activated ( 3 P-C 70 )* more efficiently and produce more singlet oxygen. This would overcome the problem of existing photosensitizers of low PDT efficiency in cancerous tissues under hypoxia. The excellent properties of PC 70 dyad make it a promising phototherapeutic agent, especially for the treatment of early- and late-stage cancers under shallow and hypoxia tissues.