Abstract
Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Animals
-
Benzhydryl Compounds / therapeutic use*
-
Cell Line, Tumor
-
Down-Regulation
-
Enzyme Inhibitors / therapeutic use*
-
Female
-
Hyperpigmentation / drug therapy*
-
Hyperpigmentation / pathology
-
Melanins / metabolism
-
Mice
-
Mice, Inbred C57BL
-
Monophenol Monooxygenase / antagonists & inhibitors
-
Oligonucleotides, Antisense / genetics
-
Oligonucleotides, Antisense / therapeutic use*
-
Prodrugs / therapeutic use
-
Receptor, Melanocortin, Type 1 / genetics
-
Receptor, Melanocortin, Type 1 / metabolism
-
Resorcinols / therapeutic use*
-
Skin / pathology
-
Skin Lightening Preparations / therapeutic use*
-
Ultraviolet Rays
Substances
-
Benzhydryl Compounds
-
Enzyme Inhibitors
-
Melanins
-
Oligonucleotides, Antisense
-
Prodrugs
-
Receptor, Melanocortin, Type 1
-
Resorcinols
-
Skin Lightening Preparations
-
Monophenol Monooxygenase
-
4-(1-phenylethyl)-1,3-benzenediol