Intraocular drug delivery is a promising approach for treatment of ocular diseases. Chemotherapeutic drugs used in retinoblastoma (RB) treatment often lead to side effects and drug resistances. Therefore, new adjuvant therapies are needed to treat chemoresistant RBs. Biocompatible gold nanoparticles (GNPs) have unique antiangiogenic properties and can inhibit cancer progression. The combination of gold and low-molecular-weight hyaluronan (HA) enhances the stability of GNPs and promotes the distribution across ocular barriers. Attached to HA-GNPs, the atrial natriuretic peptide (ANP), which diminishes neovascularization in the eye, is a promising new therapeutic agent for RB treatment. In the study presented, we established ANP-coupled HA-GNPs and investigated their effect on the tumor formation potential of chemoresistant RB cells in an in ovo chicken chorioallantoic membrane model and an orthotopic in vivo RB rat eye model. Treatment of etoposide-resistant RB cells with ANP-HA-GNPs in ovo resulted in significantly reduced tumor growth and angiogenesis compared with controls. The antitumorigenic effect could be verified in the rat eye model, including a noninvasive application form via eye drops. Our data suggest that ANP-HA-GNPs represent a new minimally invasive, adjuvant treatment option for RB.

中文翻译：

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新的视网膜母细胞瘤（RB）药物递送方法：心房钠尿肽（ANP）缀合的透明质酸包被的金纳米粒子用于眼内治疗化疗耐药性RB的抗肿瘤作用

眼内给药是治疗眼部疾病的一种有前景的方法。用于视网膜母细胞瘤（RB）治疗的化疗药物通常会导致副作用和耐药性。因此，需要新的辅助疗法来治疗化疗耐药的 RB。生物相容性金纳米颗粒 (GNP) 具有独特的抗血管生成特性，可以抑制癌症进展。金和低分子量透明质酸 (HA) 的组合增强了 GNP 的稳定性并促进跨眼屏障的分布。心房钠尿肽 (ANP) 附着在 HA-GNP 上，可减少眼内新生血管形成，是一种很有前景的 RB 治疗新治疗剂。在本研究中，我们建立了 ANP 偶联的 HA-GNP，并在鸡卵绒毛尿囊膜模型和原位体内 RB 大鼠眼模型中研究了它们对化疗耐药 RB 细胞肿瘤形成潜力的影响。与对照组相比，用 ANP-HA-GNP在卵内处理依托泊苷耐药的 RB 细胞，肿瘤生长和血管生成显着减少。抗肿瘤作用可以在大鼠眼模型中得到验证，包括通过滴眼剂的非侵入性应用形式。我们的数据表明，ANP-HA-GNP 代表了 RB 的一种新的微创辅助治疗选择。