Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages
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pISSN 1226-8372 eISSN 1976-3816
RESEARCH PAPER
Exosome-modified PLGA Microspheres for Improved Internalization into Dendritic Cells and Macrophages Gayeon You, Youngjun Kim, Joo Hang Lee, Jihyeon Song, and Hyejung Mok
Received: 8 January 2020 / Revised: 1 March 2020 / Accepted: 9 March 2020 © The Korean Society for Biotechnology and Bioengineering and Springer 2020
Abstract Considering the significance of effective antigen presentation for boosting immune responses, it is essential to develop delivery systems for antigen presenting cells (APCs; dendritic cells and macrophages). As a simple and facile way for improving delivery efficiency of PLGA microspheres (MS) into APCs, we fabricated exosomeconjugated PLGA MS via polydopamine coating in this study. Spherical micro-sized particles were first prepared by conventional water-in oil-in water (W1/O/W2) double emulsion and solvent evaporation methods and were observed by scanning electron microscopy (SEM). With increasing model protein (ovalbumin)/MS weight ratios, higher amounts of ovalbumin (OVA) were immobilized onto MS. After exosome (EXO) conjugation to MS via polydopamine coating, the amount of nitrogen was significantly increased on the surface of MS, indicating that EXO were successfully conjugated onto MS. EXO-coated dopamine MS (EXO-Dopa MS) exhibited significantly improved delivery into DC2.4 cells and RAW264.7 cells, compared with bare MS and Dopa MS. Therefore, EXODopa MS could be used as effective carriers of immune stimulating biomolecules into APCs for cancer immunotherapy. Keywords: exosomes (EXO), PLGA microspheres, dendritic cells, polydopamine coating, intracellular uptake
Gayeon You†, Youngjun Kim†, Joo Hang Lee, Jihyeon Song, Hyejung Mok* Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea Tel: +82-2-450-0448 E-mail: [email protected] †
Gayeon You and Youngjun Kim contributed equally to this work.
1. Introduction Antigen presenting cells (APCs), including dendritic cells (DCs), macrophages, and B cells, engulf exogenous antigens and present them in combination with major histocompatibility complex class II molecules, which are closely associated with T cell proliferation and activation [1,2]. Therefore, efficient delivery of antigens and immune stimulators to APCs seems to be crucial to initiate cellular and humoral immune responses for cancer immunotherapy. For these reasons, numerous efforts have been undertaken to develop techniques, such as those employing nano- and micro-sized carriers, for the effective delivery of chemicals, proteins, genetic materials, and immune stimulators to APCs [3-5]. Particle-based systems have shown more efficient delivery of biomolecules and drugs than their naked forms in terms of enhanced uptake efficiency and sustained release of the loaded materials [6,7]. According to previous studies, physicochemical properties of particles, such as size, surface charge, hydrophobicity, shape, and roughness, can affect their internalization into APCs [8-11]. Several researchers modulated
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