Multifunctional core-shell polymeric nanoparticles for transdermal DNA delivery and epidermal Langerhans cells tracking.
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.
Lee
Po-Wei
PW
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013, ROC.
Hsu
Sheng-Hsiang
SH
Tsai
Jin-Sheng
JS
Chen
Fu-Rong
FR
Huang
Pei-Jai
PJ
Ke
Cherng-Jyh
CJ
Liao
Zi-Xian
ZX
Hsiao
Chun-Wen
CW
Lin
Hao-Jan
HJ
Sung
Hsing-Wen
HW
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
D004337:Drug Carriers; D011108:Polymers; D019444:Vaccines, DNA; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA