Sub 150 nm Nanoscale Gallium Based Metal–Organic Frameworks Armored Antibiotics as Super Penetrating Bombs for Eradicating Persistent Bacteria

Abstract

Persistent bacteria, such as intracellular and biofilm bacteria, are critical challenges in clinic treatment because they are refractory to antibiotics management under the shelter of cytomembrane and biofilm. Conventional strategies to combat intracellular bacteria are using high doses of antibiotics, which may bring the risk of drug resistance, and debridement of the biofilm increases patients' pain and economic burden. Currently, the use of antibiotics is irreplaceable and it is necessary to develop new strategies to enable common antibiotics to penetrate the cytomembrane and biofilm, and then kill the bacteria. Hence, a nanoscale gallium-based metal-organic framework (GaMOF) nanoparticles that can stride across cell membranes as antibiotics carriers, disable the biofilm via disrupting bacteria Fe metabolism, and enhance the antibiotic potency for the two intractable germs is constructed. The synthesized GaMOF exhibits a high BET surface area of up to 1299.53 m 2 g −1 , uniform particle size of ≈100 nm, monodispersed spherical morphology with virus-like surfaces, and good biosafety. The nano MOF structure and Ga intrinsic inhibiting bacteria activity armored antibiotics as "super-penetrating bombs" to eradicate the two types of elusive bacteria. Moreover, intracellular bacteria-induced pyroptosis and associated inflammation in vivo are alleviated by GaMOF and cured by GaMOF united with antibiotics treatment.

A dual functional Ti-Ga alloy: inhibiting biofilm formation and osteoclastogenesis differentiation via disturbing iron metabolism

“…Iron is required for bacterial survival, growth, proliferation, and pathogenesis, which participate in DNA synthesis and energy metabolism as a cofactor. According to our previous work, Ga-based compounds could remove S. aureus biofilm [ 26 ]. Therefore, we employed proteomics analysis to explore how Ga 3+ ions affected iron metabolism.…”

“…Biofilm-associated infections and aseptic osteolysis due to the overactivation of osteoclasts are two key factors that limit the clinical application of titanium-based implants. Our previous results showed that Ga 3+ ions significantly inhibited biofilm formation and osteoclast differentiation, but the specific mechanism was unknown [ 20 , 26 ]. It will be of great clinical significance to prepare a Ti-Ga alloy to simultaneously solve the above two problems.…”

A Dual Functional Ti-Ga Alloy: Inhibiting Biofilm Formation and Osteoclastogenesis Differentiation Via Disturbing Iron Metabolism

“…Bio lm-associated infections and aseptic osteolysis due to the overactivation of osteoclasts are two key factors that limit the clinical application of titanium-based implants. Our previous results showed that Ga 3+ ions signi cantly inhibited bio lm formation and osteoclast differentiation, but the speci c mechanism was unknown [20,23]. It will be of great clinical signi cance to prepare a Ti-Ga alloy to simultaneously solve the above two problems.…”

“…Iron is required for bacterial survival, growth, proliferation, and pathogenesis, which participate in DNA synthesis and energy metabolism as a cofactor. According to our previous work, Ga-based compounds could remove S. aureus bio lm [23]. Therefore, we employed proteomics analysis to explore how Ga 3+ ions affected iron metabolism.…”

Recent nanotechnology-based strategies for interfering with the life cycle of bacterial biofilms

“…Similarly, MOFs can sustainably release the stored metal ions and thus achieve a long-term antibacterial effect. 88 Xiaoxue Yao et al prepared omniphobic porous hydrogels loaded with zinc imidazolate framework 8 (ZIF–8) nanoparticles as wound dressings. 38 Anchoring of ZIF–8 nanoparticles endowed hydrogels with a reentrant architecture and increased roughness, which was beneficial for eliminating the adhesion of pathogens.…”