title: Magnetic and Folate Functionalization Enables Rapid Isolation and Enhanced Tumor-Targeting of Cell-Derived Microvesicles.
abstract: Cell-derived microvesicles (MVs), which are biogenic nanosized membrane-bound vesicles that convey bioactive molecules between cells, have recently received attention for use as natural therapeutic platforms. However, the medical applications of MV-based delivery platforms are limited by the lack of effective methods for the efficient isolation of MVs and the convenient tuning of their targeting properties. Herein, we report the development of magnetic and folate (FA)-modified MVs based on a donor cell-assisted membrane modification strategy. MVs inherit the membrane properties of their donor cells, which allows them to be modified with the biotin and FA on their own membrane. By conjugating with streptavidin-modified iron oxide nanoparticles (SA-IONPs), the MVs can be conveniently, efficiently, and rapidly isolated from the supernatant of their donor cells using magnetic activated sorting. Moreover, the conjugated magnetic nanoparticles and FA confer magnetic and ligand targeting activities on the MVs. Then, the MVs were transformed into antitumor delivery platforms by directly loading doxorubicin via electroporation. The modified MVs exhibited significantly enhanced antitumor efficacy both in vitro and in vivo. Taken together, this study provides an efficient and convenient strategy for the simultaneous isolation of cell-derived MVs and transformation into targeted drug delivery nanovectors, thus facilitating the development of natural therapeutic nanoplatforms.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.|Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Zi-Li
authors.initials: ZL
authors.lastname: Yu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and the Institute for Advanced Studies, Key Laboratory of Analytical Chemistry for Biology and Medicine, Wuhan University , 299 Bayi Road, Wuhan 430072, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Jian-Gang
authors.initials: JG
authors.lastname: Ren
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Hou-Fu
authors.initials: HF
authors.lastname: Xia
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Sa
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Jun-Yi
authors.initials: JY
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, and the Institute for Advanced Studies, Key Laboratory of Analytical Chemistry for Biology and Medicine, Wuhan University , 299 Bayi Road, Wuhan 430072, P. R. China.
authors.forename: Dai-Wen
authors.initials: DW
authors.lastname: Pang
authors.affiliation: Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine of Ministry of Education, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.|Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University , Wuhan 430079, P. R. China.
authors.forename: Gang
authors.identifier: 0000-0003-3332-3511
authors.initials: G
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000737:chemistry*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019809:Streptavidin / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D019809:Streptavidin; D005492:Folic Acid
keywords: cancer therapy; drug delivery; dual targeting; magnetic modification; microvesicle