Injectable bio-responsive hydrogel for therapy of inflammation related eyelid diseases

Eyelid plays a vital role in protecting the eye from injury or infection.Inflammation related eyelid diseases,such as blepharitis,are the most common ocular disorders that affect human’s vision and quality of life.Due to the physiological barriers and anatomical structures of the eye,the bioavailability of topical administrated therapeutics is typically less than 5%.Herein,we developed a bio-responsive hydrogel drug delivery system using a generally recognized as safe compound,triglycerol monostearate(TG-18),for in-situ eyelid injection with sustained therapeutics release.In vitro,drug release and disassembly time of Rosiglitazone loaded hydrogel(Rosi-hydrogel)were estimated in the presence or absence of MMP-9,respectively.Moreover,the disassembly of TG-18 hydrogel was evaluated with 9-month-old and 12-month-old mice in vivo.Owing to the bio-responsive nature of Rosi-hydrogel,the on-demand Rosiglitazone release is achieved in response to local enzymes.These findings are proved by further evaluation in the age-related meibomian gland dysfunction mice model,and the bio-responsive hydrogel is used as an in-situ injection to treat eyelid diseases.Taken together,the in-situ eyelid injection with sustained drug release opens a window for the therapy of inflammation related eyelid diseases.

Bio-assembled smart nanocapsules for targeted delivery of KRAS shRNA and cancer cell bioimage

The five-year survival rate for pancreatic cancer is less than 5%. However, the current clinical multimodal therapy combined with first-line chemotherapy drugs only increases the patient’s median survival from 5.0 months to 7.2 months. Consequently, a new strategy of cancer treatments is urgently needed to overcome this high-fatality disease. Through a series of biometric analyses, we found that KRAS is highly expressed in the tumor of pancreatic cancer patients, and this high expression is closely related to the poor prognosis of patients. It shows that inhibiting the expression of KRAS has great potential in gene therapy for pancreatic cancer. Given those above, we have exploited the possibility of targeted delivery of KRAS shRNA with the intelligent and bio-responsive nanomedicine to detect the special oxidative stress microenvironment of cancer cells and realize efficient cancer theranostics. Our observations demonstrate that by designing the smart self-assembled nanocapsules of melanin with fluorescent nanoclusters we can readily achieve the bio-recognition and bioimaging of cancer cells in biological solution or serum.The self-assembled nanocapsules can make a significant bio-response to the oxidative stress microenvironment of cancer cells and generate fluorescent zinc oxide Nanoclusters in situ for targeted cell bioimaging. Moreover, it can also readily facilitate cancer cell suppression through the targeted delivery of KRAS shRNA and low-temperature hyperthermia. This raises the possibility to provide a promising theranostics platform and self-assembled nanomedicine for targeted cancer diagnostics and treatments through special oxidative stress-responsive effects of cancer cells.

Verteporfin-mediated on/off photoswitching functions synergistically to treat choroidal vascular diseases

Choroidal vascular diseases,such as age-related macular degeneration,are the leading cause of vision impairment and are characterized by pathological angiogenesis.Verteporfin-mediated photodynamic therapy is a current strategy that selectively occludes choroidal neovasculature.However,the clinically used large-dose systemic administration increases the risk of systemic adverse events,such as phototoxicity to superficial tissues.In this study,we developed an in situ verteporfin delivery system with a photoswitching synergistic function that disassembles in response to intraocular inflammatory enzymes.Under light-on conditions,verteporfin-mediated photodynamic therapy effectively occurs and this leads to vascular occlusion.Under light-off conditions,non-photoactive verteporfin negatively regulates vascular endothelial growth factor-induced angiogenesis as a yes-associated protein inhibitor.Taken together,our system serves as an intraocular verteporfin reservoir to improve the bioavailability of verteporfin by innovatively exploiting its photochemical and biological functions.This work provides a promising strategy with synergistic antiangiogenic effects for the treatment of choroidal vascular diseases.