Yiyang Guo,Yubin Ma,Xin Chen,Min Li,Xuehu Ma,Gang Cheng,Changying Xue,Yi Y. Zuo,Bingbing Sun
The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle–mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle–mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.
Xiaoting Gao,Lei Yan,Wei Zhang,Yuanliang Lv,Peiyan Ou,Ruiqiang Hang,Ang Gao,Liping Tong,Paul K. Chu,Huaiyu Wang
Carbon monoxide (CO) has great potential in the therapy of osteoarthritis (OA), but its controllable delivery in vivo is still an intractable problem. To optimize CO gas therapy for OA, a stable CO release platform with multi-stimulus responsiveness must be designed. Herein, we describe a local delivery system (Fe 3 (CO) 12 @Croc-PEG5K) for near-infrared fluorescence (NIRF) imaging-guided photothermal treatment and CO gas synergistic therapy. As a nano gas tank, Fe 3 (CO) 12 @Croc-PEG5K releases CO on-demand under near infrared (NIR) laser irradiation, scavenges free radicals and regulates the pH in the OA microenvironment , and relieves the inflammatory response of macrophages to maintain the vitality of chondrocytes . Furthermore, the pH-dependent NIRF imaging properties of Fe 3 (CO) 12 @Croc-PEG5K can be exploited to determine the administration interval and auto-monitor the curative effects during the therapeutic process. Owing to these merits, the photothermal and CO gas synergistic therapy mediated by Fe 3 (CO) 12 @Croc-PEG5K can be optimized to deliver outstanding therapeutic performance in vivo , as demonstrated by the OA rat model. Our study is the first to validate the therapeutic effect of CO against OA in vivo , reveals a promising strategy for precision medicine pertaining to the treatment of OA and broadens the scope of CO gas therapy.
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