Camouflage Nanoparticles Enable in Situ Bioluminescence-Driven Optogenetic Therapy of Retinoblastoma

Abstract

Optogenetic therapy has emerged as a promising technique for the treatment of ocular diseases; however, most optogenetic tools rely on external blue light to activate the photoswitch, whose relatively strong phototoxicity may induce retinal damage. Herein, we present the demonstration of camouflage nanoparticle-based vectors for in situ bioluminescence-driven optogenetic therapy of retinoblastoma. In biomimetic vectors, the photoreceptor CRY2 and its interacting partner CIB1 plasmid are camouflaged with folic acid ligands and luciferase NanoLuc-modified macrophage membranes. To conduct proof-of-concept research, this study employs a mouse model of retinoblastoma. In comparison to external blue light irradiation, the developed system enables an in situ bioluminescence-activated apoptotic pathway to inhibit tumor growth with greater therapeutic efficacy, resulting in a significant reduction in ocular tumor size. Furthermore, unlike external blue light irradiation, which causes retinal damage and corneal neovascularization, the camouflage nanoparticle-based optogenetic system maintains retinal structural integrity while avoiding corneal neovascularization.

Biomedical Applications of Cell Membrane‐Based Biomimetic Nano‐Delivery System

“…The prevailing and widely adopted technique for coating various NPs with CMs involves multiple rounds of co-extrusion through porous membranes of diverse sizes. [21,[36][37][38][39][40][41][42][43][44] This approach has been successfully applied to generate uniform and anticipated sizes of CM-NPs. Nevertheless, this method suffers the limitation of material loss due to adhesion with the film, making mass production challenging.…”

“…[107] Inspired by the effectiveness of optogenetic tools in manipulating protein activity using blue light illumination, which has shown promising results in treating various diseases, such as retinal degenerative diseases, glaucoma, and uveal melanoma, Ding et al examined MNPs-based drug delivery for optogenetic therapy in managing RB. [39] To generate MNPs, the plasmids encoding photoreceptor CRY2 and its interacting partner CIB1 were coated onto MNPs using the co-extrusion method. An intravitreal injection of the MNPs into a mouse model of RB, led to a more profound suppression of the tumor and a more significant reduction in ocular tumor size, compared to the PBS group or the external blue light irradiation group.…”

Beyond External Light: On-Spot Light Generation or Light Delivery for Highly Penetrated Photodynamic Therapy

“…(d) Long-term monitoring of luminescence variation in different groups. (e) Slit lamp photography of the eyes in different groups . Reprinted with permission from ref .…”

“…(e) Slit lamp photography of the eyes in different groups . Reprinted with permission from ref . Copyright 2023 American Chemical Society.…”

“…He et al also developed the demonstration of a BL-driven optogenetic tool for retinoblastoma therapy. 105 The optogenetic system (referred as M/Lip-FA-NLuc@PP) is composed of photoreceptor cryptochrome 2 (CRY2), its interacting partner calcium and integrin-binding protein 1 (CIB1) plasmid, folic acid (FA) ligand, and luciferase NanoLuc-modified macrophage membranes. Under the excitation of BL, CIB1 specifially binds to CRY2, and FADD binds to FAS to activate the caspase-3mediated apoptotic signaling pathway (Figure 25a).…”