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Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology. Full article

The newly developed multimodal imaging system combining raster-scan optoacoustic (OA) microscopy and fluorescence (FL) wide-field imaging was used for characterizing the tumor vascular structure with 38/50 μm axial/transverse resolution and assessment of photosensitizer fluorescence kinetics during treatment with novel theranostic agents. A multifunctional photoactivatable multi-inhibitor liposomal (PMILs) nano platform was engineered here, containing a clinically approved photosensitizer, Benzoporphyrin derivative (BPD) in the bilayer, and topoisomerase I inhibitor, Irinotecan (IRI) in its inner core, for a synergetic therapeutic impact. The optimized PMIL was anionic, with the hydrodynamic diameter of 131.6 ± 2.1 nm and polydispersity index (PDI) of 0.05 ± 0.01, and the zeta potential between −14.9 ± 1.04 to −16.9 ± 0.92 mV. In the in vivo studies on BALB/c mice with CT26 tumors were performed to evaluate PMILs’ therapeutic efficacy. PMILs demonstrated the best inhibitory effect of 97% on tumor growth compared to the treatment with BPD-PC containing liposomes (PALs), 81%, or IRI containing liposomes (L-[IRI]) alone, 50%. This confirms the release of IRI within the tumor cells upon PMILs triggering by NIR light, which is additionally illustrated by FL monitoring demonstrating enhancement of drug accumulation in tumor initiated by PDT in 24 h after the treatment. OA monitoring revealed the largest alterations of the tumor vascular structure in the PMILs treated mice as compared to BPD-PC or IRI treated mice. The results were further corroborated with histological data that also showed a 5-fold higher percentage of hemorrhages in PMIL treated mice compared to the control groups. Overall, these results suggest that multifunctional PMILs simultaneously delivering PDT and chemotherapy agents along with OA and FL multi-modal imaging offers an efficient and personalized image-guided platform to improve cancer treatment outcomes. Full article