Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified catio...Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan.The hydrogel microsphere,consisting of photocurable GelMA and ChSMA,were fabricated using a microfluidic platform for cargo delivery.The cationic targeting nanoparticle-hydrogel microsphere@-fucoidan(CTNM@FU)possess three-step programmable characteristics that enable responsive transport toward injured cartilage,effective penetration of the cartilage matrix and selective entry into chondrocytes,escape from lysosomes,and release of bio-activators.The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU.Intraarticular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited de novo cartilage formation.Mechanistically,CTNM@FU protected cartilage by activating SIRT3,enhancing mitochondrial energy and countering aging.Collectively,a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.展开更多
基金supported by grants from the National Nature Science Foundation of China(82272494,82472452,82402864)the National Key R&D Program of China(2022YFC2502902)+5 种基金the Key Project of Jiangsu Health Commission(K2023079)the Natural Science Foundation of Jiangsu Province(BK20240368)the Basic Research Pilot Project Suzhou(SSD2024062)the China Postdoctoral Science Foundation(2024M762313)Boxi Youth Natural Science Foundation(BXQN2023014)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Treating osteoarthritis(OA)presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release.Here,the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan.The hydrogel microsphere,consisting of photocurable GelMA and ChSMA,were fabricated using a microfluidic platform for cargo delivery.The cationic targeting nanoparticle-hydrogel microsphere@-fucoidan(CTNM@FU)possess three-step programmable characteristics that enable responsive transport toward injured cartilage,effective penetration of the cartilage matrix and selective entry into chondrocytes,escape from lysosomes,and release of bio-activators.The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU.Intraarticular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited de novo cartilage formation.Mechanistically,CTNM@FU protected cartilage by activating SIRT3,enhancing mitochondrial energy and countering aging.Collectively,a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.
