Tailored polysaccharide entrapping metal-organic framework for RNAi therapeutics and diagnostics in atherosclerosis

Abstract

Metal-organic frameworks (MOFs) hold promise as theranostic carriers for atherosclerosis. However, to further advance their therapeutic effects with higher complexity and functionality, integrating multiple components with complex synthesis procedures are usually involved. Here, we reported a facile and general strategy to prepare multifunctional anti-atherosclerosis theranostic platform in a single-step manner. A custom-designed multifunctional polymer, poly(butyl methacrylate-co-methacrylic acid) branched phosphorylated β-glucan (PBMMA-PG), can effectively entrap different MOFs via coordination, simultaneously endow the MOF with enhanced stability, lesional macrophages selectivity and enhanced endosome escape. Sequential ex situ characterization and computational studies elaborated the potential mechanism. This facile post-synthetic modification granted the administered nanoparticles atherosclerotic tropism by targeting Dectin-1+ macrophages, enhancing in situ MR signal intensity by 72 %. Delivery of siNLRP3 effectively mitigated NLRP3 inflammasomes activation, resulting a 43 % reduction of plaque area. Overall, the current study highlights a simple and general approach for fabricating a MOF-based theranostic platform towards atherosclerosis conditioning, which may also expand to other indications targeting the lesional macrophages.

Keywords

• Polysaccharide
• Gene therapy
• RNAi therapeutics
• Atherosclerosis
• Metal-organic framework