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제 목 : Multifunctional Inorganic Nanoparticles for Modulation of Hypoxic Microenvironments
연 사 : 이노현 교수(국민대학교)
일 시 : 2020년 10월 13일(화) 오후 4시 30분
방번호: 170 400 9240
Multifunctional Inorganic Nanoparticles for Modulation of Hypoxic Microenvironments
Due to their unique physicochemical properties, inorganic nanoparticles (NPs) have emerged as novel imaging, diagnostic, and therapeutic agents for the future biomedical field. In particular, hypoxic inflammatory microenvironments, which is often found at disease sites in the body, can be easily controlled using NPs with various combinations. Catalytic NPs continuously generate oxygen using intracellular hydrogen peroxide in the hypoxic microenvironment. They can also control the phenotype of macrophages in the inflammatory microenvironment, alleviating the inflammation. Moreover, immune cell can be targeted using the NPs functionalized with targeting moieties, enabling the delivery of the functional NPs to inflammatory microenvironments. I would like to describe the applications of multifunctional inorganic NPs for modulation of hypoxic and inflammatory microenvironments.
Firstly, biocompatible manganese ferrite NP-anchored mesoporous silica NPs (MFMSNs) were designed to overcome hypoxia, consequently enhancing the therapeutic efficiency of photodynamic therapy (PDT). By exploiting the continuous oxygen-evolving property of manganese ferrite NPs through the Fenton reaction, MFMSNs relieved hypoxic condition using a small amount of NPs and improved therapeutic outcomes of PDT for tumors in vivo.
Secondly, manganese ferrite and ceria NP-anchored mesoporous silica NPs (MFC-MSNs) that can synergistically scavenge reactive oxygen species (ROS) and produce oxygen for M1 macrophage reduction and M2 macrophage induction for rheumatoid arthritis (RA) treatment. MFC-MSNs exhibited a synergistic effect on O2 generation attributed to hydroxyl complementary reaction of ceria NPs scavenging the intermediate hydroxyl radical generated by manganese ferrite NPs during the Fenton reaction, leading to efficient polarization of M1 to M2 macrophages. Intra-articular administration of MFC-MSNs to RA-suffering rats alleviated hypoxia, inflammation, and pathological features in the joint.
Lastly, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to delivery drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies were modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h resulted in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which served as active vectors into tumor interiors. The CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model.