Intrinsic Ultrahigh Drug/miRNA Loading Capacity of Biodegradable Bioactive Glass Nanoparticles Toward Highly Efficient Pharmaceutical Delivery

The lack of safe and efficient drug and gene delivery vectors has become a major obstacle for the clinical applications of drug and nonviral gene therapy. To date, for nonviral gene vectors, most studies are focused on cationic polymers, liposomes, and modified inorganic nanoparticles which have shown high cellular toxicity, low transfection efficiency, or nondegradation. Additionally, few biodegradable biomaterials demonstrate intrinsic high binding abilities to both drug and gene. Bioactive glasses (BGs) have achieved successful applications in bone regeneration due to their high biocompatibility and biodegradation. Here, for the first time, we demonstrate the intrinsic ultrahigh drug and miRNA binding ability of bioactive glass nanoparticles (BGNs) without any cationic polymer modification. BGNs demonstrate an over 45-fold improvement in hydrophilic drug loading (diclofenac sodium) and 7-fold enhancement in miRNA binding over their corresponding silica nanoparticles. The hydrophilic drug loading ability of BGNs (>45 wt % loading) is also higher than that of most other reported inorganic nanoparticles, including mesoporous silica nanoparticles. BGNs show significantly lower cytotoxicity and higher cellular uptake and miRNA transfection efficiency compared to those of commercial transfection reagents polyethylenimine and lipofectamine 3000. Our results demonstrate that BGNs may become a new competitive vehicle for drug and gene delivery applications. This study may also provide a new strategy to develop novel biomaterials with intrinsic drug and gene binding ability for disease therapy.