title: Yeast Microcapsule-Mediated Targeted Delivery of Diverse Nanoparticles for Imaging and Therapy via the Oral Route.
abstract: Targeting of nanoparticles to distant diseased sites after oral delivery remains highly challenging due to the existence of many biological barriers in the gastrointestinal tract. Here we report targeted oral delivery of diverse nanoparticles in multiple disease models, via a "Trojan horse" strategy based on a bioinspired yeast capsule (YC). Diverse charged nanoprobes including quantum dots (QDs), iron oxide nanoparticles (IONPs), and assembled organic fluorescent nanoparticles can be effectively loaded into YC through electrostatic force-driven spontaneous deposition, resulting in different diagnostic YC assemblies. Also, different positive nanotherapies containing an anti-inflammatory drug indomethacin (IND) or an antitumor drug paclitaxel (PTX) are efficiently packaged into YC. YCs containing either nanoprobes or nanotherapies may be rapidly endocytosed by macrophages and maintained in cells for a relatively long period of time. Post oral administration, nanoparticles packaged in YC are first transcytosed by M cells and sequentially endocytosed by macrophages, then transported to neighboring lymphoid tissues, and finally delivered to remote diseased sites of inflammation or tumor in mice or rats, all through the natural route of macrophage activation, recruitment, and deployment. For the examined acute inflammation model, the targeting efficiency of YC-delivered QDs or IONPs is even higher than that of control nanoprobes administered at the same dose via intravenous injection. Assembled IND or PTX nanotherapies orally delivered via YCs exhibit remarkably potentiated efficacies as compared to nanotherapies alone in animal models of inflammation and tumor, which is consistent with the targeting effect and enhanced accumulation of drug molecules at diseased sites. Consequently, through the intricate transportation route, nanoprobes or nanotherapies enveloped in YC can be preferentially delivered to desired targets, affording remarkably improved efficacies for the treatment of multiple diseases associated with inflammation.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.|Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.|State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Songling
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.|Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.|Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Radiation, Southwest Hospital, Third Military Medical University , Chongqing 400038, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Genghao
authors.initials: G
authors.lastname: Gong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau , Taipa, Macau, China.
authors.forename: Ruibing
authors.identifier: 0000-0001-9489-4241
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biologic and Materials Sciences, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.|Institute of Materia Medica, College of Pharmacy, Third Military Medical University , Chongqing 400038, China.
authors.forename: Jianxiang
authors.identifier: 0000-0002-0984-2947
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules; D002279:Carcinoma 256, Walker / Q000000981:diagnostic imaging / Q000188:drug therapy; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry*; D007249:Inflammation / Q000000981:diagnostic imaging / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D002214:Capsules; D004337:Drug Carriers; D017239:Paclitaxel; D007213:Indomethacin
keywords: Yeast; drug delivery; imaging; microcapsule; nanoparticle; oral targeting