Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
Multidrug resistance (MDR), as a major obstacle in cancer therapy, has resulted in over 90% of cancer chemotherapeutic failure. Mesoporous silica nanospheres (MSNs) have been demonstrated to be tuned with large pore sizes, mediating the MDR-reversal effects. However, the study that surface functionality of the large pore sized-MSNs affects the MDR-overcoming effects hasn’t been extensively studied. In this study, we developed a new dendrimer-like MSNs delivery system based on a rational synthesis strategy and further modified MSNs with various surface functionalities to evaluate their roles in overcoming cancer MDR. Our results showed that the small particle sized-MSNs could be fabricated with dendrimer-like internal structure, resulting in the large pore size of 9 nm. Surface functionality of MSNs, especially hydroxylation and carboxylation, largely improved the intra-nuclear delivery and therapeutic efficiency of DOX for MCF7/ADR cells, which was not up to inhibiting P-gp expression but significantly increasing the intracellular drug accumulation of over 90% even under the strong drug efflux. This study indicates that surface functionality design strategy may display the potential of the large pore sized-MSNs as the efficient chemotherapeutic carriers to combat MDR.
危险品化学品经营许可证（带存储）