PLGA protein nanocarrier with made-to-order fluorescence/MRI/PET imaging modalities

Developing multifunctional and biocompatible drug delivery nanoplatforms that integrate high drug loading capacity together with multiple imaging modalities while at the same time avoiding cross interferences is extremely challenging. Here, chemical modifications of poly(lactic-co-glycolic acid) (PLGA) to produce biocompatible nanocapsules (NCs) that incorporate multimodal imaging moieties for in vivo formulations are reported. The chemical synthetic routes to endow the PLGA with a magnetic resonance imaging (MRI) reporter, two fluorescence imaging probes and a positron emission tomography (PET) reporter are presented. Then a made-to-order modular integration of these imaging reporters into the shell of the PLGA NCs is successfully achieved without affecting the morphochemical properties of the nanocarrier or the drug loading capacity. Biodistribution of the NCs are monitored by MRI/PET/NIRF in vivo and the results from the different techniques analyzed comparatively. The viabilities of two different human endothelial cells in vitro show no toxicity for NCs concentration up to 100 μg mL-1. The morbidity of mice for 2 weeks after the systemic administration and the hepatic/pancreatic enzymes at plasma level show in vivo biosafety of the NCs. In summary, the new theranostic PLGA nanoplatform presented here shows versatile in vivo multimodal imaging capabilities, excellent biosafety and over 1 wt% protein loading