Targeted Noninvasive Treatment of Choroidal Neovascularization by Hybrid Cell-Membrane-Cloaked Biomimetic Nanoparticles

Abstract

Choroidal neovascularization (CNV) is the leading cause of vision loss in many blinding diseases, but current antiangiogenic therapies with invasively intravitreal injection suffer from poor patient compliance and a rate of devastating ocular complications. Here, we develop an alternative antiangiogenic agent based on hybrid cell-membrane-cloaked nanoparticles for noninvasively targeted treatment of CNV. The retinal endotheliocyte membrane coating provides as-fabricated nanoagents with homotypic targeting capability and binding ability to the vascular endothelial growth factor. The fusion of red blood cell membranes protects the hybrid membrane-coated nanoparticles from phagocytosis by macrophages. In a laser-induced wet age-related macular degeneration mouse model, a significantly enhanced accumulation is observed in CNV regions after intravenous delivery of the hybrid membrane-coated nanoparticles. Moreover, an excellent therapeutic efficacy is achieved in reducing the leakage and area of CNV. Overall, the biomimetic antiangiogenic nanoagents provide an effective approach for noninvasive treatment of CNV.

A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis

“…Nanoparticles camouflaged by cell membrane have the characteristics of both source cell membrane and nano-drug nucleus. Currently, the membranes used to package nanoparticles come from red blood cells, white blood cells, platelets, macrophages, T lymphocytes, stem cells, and tumor cells [ 47 – 50 ]. Nanoparticles have different functions during drug delivery due to different cell membrane sources.…”

Cell Membrane-Cloaked Nanotherapeutics for Targeted Drug Delivery

“…The hybrid membrane can be simply prepared by fusing cell membranes from different cell sources with sonication and mechanical extrusion, and thus can perform increasingly complex tasks within biologically relevant contexts [2,70,71]. Thus, a hybrid membrane coating strategy could be a facile and effective way to enhance nanoparticle functionality [72].…”

“…For example, RBC-cancer cell hybrid membranes exhibited both long circulation and homotypic tumor-targeting properties after being coated onto nanoparticles [2]. Retinal endotheliocyte-RBC (REC-RBC) hybrid membranes obtained homotypic targeting ability, binding ability to the vascular endothelial growth factors, and immune evasion [70]. Therefore, REC-RBC membrane-coated nanoparticles drastically accumulated in choroidal neovascularization regions as compared to REC or RBC membrane-coated nanoparticles.…”

“…In comparison to that of native stem cell membrane-coated nanoparticles, CXCR4-expressed stem cell membrane-coated nanoparticles facilitated nanoparticle accumulation in ischemic tissues by two-fold, and subsequently released VEGF, led to enhanced blood reperfusion, and improved limb salvage in a hindlimb ischemia model of peripheral vascular disease. Recently, Li et al [70] reported that RBC-REC hybrid membrane-coated nanoparticles could act as an antiangiogenic material for targeted treatment of choroidal neovascularization (CNV), which is the leading cause of vision loss in many blinding diseases. Due to the RBC membrane fraction, the nanoparticle phagocytosis by macrophages was reduced, leading to the enhanced accumulation in CNV regions rather than in the liver.…”

Homotypic targeting of immunomodulatory nanoparticles for enhanced peripheral and central immunity

“…In addition, surface coating with cell membranes can greatly enhance the biocompatibility and circulation lifetime of NP and promote their cellular uptake. 40 , 41 , 42 …”