An anti-GD2 aptamer-based bifunctional spherical nucleic acid nanoplatform for synergistic therapy targeting MDM2 for retinoblastoma.

Retinoblastoma (RB) is a type of pediatric solid tumor in the fundus. The lack of precision therapies combined with the difficulty of delivering small interfering RNA (siRNA) into the eyes means that there is currently no nucleic acid-based therapy for RB in clinical practice. Here, we reported on anti-GD2 and glutathione-responsive spherical nucleic acids (SNAs), loaded with siRNA and the inhibitor NVP-CGM097, which jointly blocked the oncogenic factor n in RB cells (Y79 and WERI-RB-1). The SNAs were formed through the self-assembly of bifunctional cholesterol amphiphiles containing aptamers that specifically targeted GD2-positive RB cells, allowing for the formation of an SNA with a dense DNA shell. The aptamer/siRNA component functioned both as a carrier and a payload, enhancing the specific recognition and delivery of both components and constituting an active agent for MDM2 regulation. Following SNA endocytosis by RB cells, siRNA and NVP-CGM097 were released from the SNA particles by glutathione, which synergistically blocked the MDM2-p53 pathway, increasing p53 protein content and inducing cell apoptosis. This study showed a potent antitumor effect following intravitreal injection of SNAs in Y79 tumor-bearing mice through clinical manifestation and tumor pathological analysis. In hematological analysis and hepatotoxicity assays, SNAs were safer for mice than melphalan, the favored drug for treating RB in clinical practice. Our results illustrated the potential of intravitreally injected SNAs as a precision medicine for treating RB.

Surgical Outcomes of Myopic Foveoschisis According to the ATN Classification System.

INTRODUCTION: This study compared the surgical outcomes in eyes with myopic foveoschisis (MF) according to the recently developed ATN classification system. METHODS: This was an observational case series of 64 consecutive eyes that underwent vitrectomy for MF. Eyes were classified into severe myopic maculopathy (MM) (n = 43) and non-severe MM (n = 21) groups according to the ATN classification system. The primary outcome measures constituted best-corrected visual acuity (BCVA) and anatomical changes. RESULTS: In total, BCVA improved from 0.97 to 0.53 (P < 0.001) after surgery. The ATN score was significantly lower in the eyes with vision improvement than those without vision improvement (P < 0.001). In the subgroup, BCVA improved from 0.79 to 0.28 in the non-severe MM group (P < 0.001), and improved from 1.05 to 0.65 in the severe MM group (P = 0.001) after surgery. The non-severe MM group achieved better postoperative BCVA (P = 0.001) and were more likely to gain vision improvement (P < 0.001) after surgery compared with the severe MM group. Anatomical success was achieved in 62 of the 64 eyes (96.88%). Two eyes with anatomical failure developed full-thickness macular holes postoperatively; both were in the severe MM group. CONCLUSIONS: For patients with MF, different severity of MM based on ATN classification could lead to a significantly different prognosis after surgery. For patients with high ATN scores, the operative decision should be made cautiously for the worse anatomical and visual prognosis. ATN system is instructive in making operative proposals for MF.

On the basis of the newly developed ATN classification system, we found significant differences in postoperative visual acuity, the rate of vision improvement, and the rate of primary retinal reattachment after vitrectomy between the severe and non-severe myopic maculopathy groups in patients with myopic foveoschisis.