title: Multifunctional core-shell polymeric nanoparticles for transdermal DNA delivery and epidermal Langerhans cells tracking.
abstract: Skin is a highly immune-reactive tissue containing abundant antigen-presenting cells such as Langerhans cells (LCs), and thus is a favorable site for DNA immunization. This study developed a multifunctional core-shell nanoparticle system, which can be delivered transdermally into the epidermis via a gene gun, for use as a DNA carrier. The developed nanoparticles comprised a hydrophobic PLGA core and a positively-charged glycol chitosan (GC) shell. The core of the nanoparticles was used to load fluorescent quantum dots (QDs) for ultrasensitive detection of Langerhans cell migration following transdermal delivery, while a reporter gene was electrostatically adsorbed onto the GC shell layer of the nanoparticles. Results of fluorescence spectrophotometry, transmission electron microscopy, energy dispersive X-ray analysis, and X-ray diffraction measurement confirmed that the prepared nanoparticles had a core-shell structure with QDs in their core area. The surface charge of nanoparticles depended strongly on pH environment, enabling the intracellular release of the loaded DNA via a pH-mediated mechanism. Using a mouse model, this study demonstrated that bombardment of nanoparticles transfected DNA directly into LCs present in the epidermis; the transfected LCs then migrated and expressed the encoded gene products in the skin draining lymph nodes. These observation results suggest that the developed nanoparticle system is suitable for monitoring and fine-tuning important functional aspects of the immune system, in conjunction with the loaded fluorescence, and thus has potential for use in immunotherapy and vaccine development.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
authors.forename: Po-Wei
authors.initials: PW
authors.lastname: Lee
authors.forename: Sheng-Hsiang
authors.initials: SH
authors.lastname: Hsu
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: Tsai
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Chen
authors.forename: Pei-Jai
authors.initials: PJ
authors.lastname: Huang
authors.forename: Cherng-Jyh
authors.initials: CJ
authors.lastname: Ke
authors.forename: Zi-Xian
authors.initials: ZX
authors.lastname: Liao
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Hsiao
authors.forename: Hao-Jan
authors.initials: HJ
authors.lastname: Lin
authors.forename: Hsing-Wen
authors.initials: HW
authors.lastname: Sung
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism*; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D045663:Quantum Dots; D014162:Transfection / Q000379:methods; D019444:Vaccines, DNA
chemical_list: D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA