In vivo assembly drug delivery strategy based on ultra-small nanoparticles: Toward high drug permeation and accumulation for CNV treatment

Corneal neovascularization (CNV) is one of the common blinding factors worldwide and how to treat CNV effectively is a knotty problem in clinical practice. Although, photothermal therapy (PTT) has been widely investigated in CNV management, it is still limited by the effective delivery of photothermal agents. Hereby, we proposed and validated an in vivo assembly drug delivery strategy, which composed of vascular targeting molecule (RGD-Bis(DPA-Zn), DRUG-1) and ultra-small nanoparticles (AuPt-ICG, DRUG-2). DRUG-2, with PTT and photoacoustic imaging (PAI) properties, could be co-assembled with DRUG-1 to form larger DRUG-1@2 nanocluster, accompanied by performance gains. To treat CNV, DRUG-1 was topically administrated via eye drops; and trapped at the target by the in situ co-assembled with DRUG-1, during which the dual-PAI system was applied to trace drug enrichment; finally, a safe NIR irradiation strategy was implemented to realize efficient CNV elimination. Moreover, the DRUG-1/2 -combined treatment demonstrated better biosecurity and broke new ground for CNV theranostics.