title: Improved double emulsion technology for fabricating autofluorescent microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents.
abstract: The aim of this study is to explore an improved double emulsion technology with in situ reaction of lysine (Lys) and glutaraldehyde (GA) for fabricating autofluorescent Lys-poly(lactic-co-glycolic acid)-GA (Lys-PLGA-GA) microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents. Scanning electron microscope (SEM) and static light scattering (SLS) results show that 80% of the Lys-PLGA-GA microcapsules are larger than 1.0 μm and 90% of them are smaller than 8.9 μm. SEM and laser confocal scanning microscope (LCSM) data demonstrate that the structure of our Lys-PLGA-GA microcapsules is hollow. Compared with the FT-IR spectrum of PLGA microcapsules, a new peak at 1,644 cm(-1) in that of Lys-PLGA-GA microcapsules confirms the formed Schiff base in Lys-PLGA-GA microcapsules. LCSM images and fluorescence spectra show that our Lys-PLGA-GA microcapsules exhibit bright and stable autofluorescence without conjugation to any fluorescent agent, which can be ascribed to the n-π transitions of the CN bonds in the formed Schiff base. Our autofluorescent Lys-PLGA-GA microcapsules might have more wide applications than traditional fluorescent dyes because their excitation and emission spectra are both broad. The fluorescence intensity can also be tuned by the feeding amount of Lys and GA. The MTT assays reveal that the autofluorescent microcapsules are biocompatible. The results of fluorescent imaging in cells and in vitro ultrasonic imaging demonstrate the feasibility of our autofluorescent Lys-PLGA-GA microcapsules as ultrasonic/fluorescent dual-modality contrast agents. This novel ultrasonic/fluorescent dual-modality contrast agent might have potential for a variety of biological and medical applications.
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China.
authors.forename: An
authors.initials: A
authors.lastname: Gong
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China.
authors.forename: Xuehua
authors.initials: X
authors.lastname: Ma
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China.
authors.forename: Lingchao
authors.initials: L
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Ren
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China. Electronic address: shenzheyu@nimte.ac.cn.
authors.forename: Zheyu
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, & Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology & Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China. Electronic address: aiguo@nimte.ac.cn.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Wu
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D002214:Capsules / Q000737:chemistry; D002470:Cell Survival; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D004655:Emulsions / Q000737:chemistry; D005453:Fluorescence; D005976:Glutaral / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D061986:MCF-7 Cells; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014407:Tumor Cells, Cultured; D014465:Ultrasonics
chemical_list: D001672:Biocompatible Materials; D002214:Capsules; D003287:Contrast Media; D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008239:Lysine; D005976:Glutaral
keywords: Autofluorescent microcapsules; Double emulsion technology; Poly(lactic-co-glycolic acid); Schiff base; Ultrasonic/fluorescent dual-modality contrast agents