title: Transdermal Gene Delivery by Functional Peptide-Conjugated Cationic Gold Nanoparticle Reverses the Progression and Metastasis of Cutaneous Melanoma.
abstract: Permeability barrier imposed by stratum corneum makes an extreme challenge for the topical delivery of plasmid DNA (pDNA), which is widely used in gene therapy. Existing techniques to overcome the skin barrier for bio-macromolecules delivery rely on sophisticated mechanical devices. It is still a big challenge to treat the skin cancer, for example, melanoma, that initiates in the dermal layer by topical gene therapy. To facilitate the skin penetration of pDNA deeply into the melanoma tissues, we here present a cell-penetrating peptide and cationic poly(ethyleneimine) conjugated gold nanoparticle (AuPT) that can compact the pDNAs into cationic nanocomplexes and penetrate through the intact stratum corneum without any additional enhancement used. Moreover, the AuPT is highly efficient in stimulating the intracellular uptake and nuclear targeting of the pDNAs in cells, which guarantees the effective transfection. This study provides evidence that penetrating peptide conjugated cationic gold nanoparticle offers a promising vehicle for both the skin penetration and transfection of pDNAs, possessing great potential in topical gene therapy.
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Niu
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Yan-Fen
authors.initials: YF
authors.lastname: Huang
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Yee-Song
authors.initials: YS
authors.lastname: Chong
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology , Macau, P. R. China.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University , Hangzhou 310027, P. R. China.
authors.forename: Zheng-Wei
authors.initials: ZW
authors.lastname: Mao
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.|State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology , Macau, P. R. China.
authors.forename: Li-Hua
authors.identifier: http://orcid.org/0000-0001-9763-383X
authors.initials: LH
authors.lastname: Peng
authors.affiliation: Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou 310058, P. R. China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
mesh_terms: D000279:Administration, Cutaneous; D018014:Gene Transfer Techniques; D006046:Gold; D006801:Humans; D008545:Melanoma; D053768:Metal Nanoparticles; D012867:Skin; D012878:Skin Neoplasms
chemical_list: D006046:Gold
keywords: cationic gold nanoparticle; cell-penetrating peptide; melanoma; plasmid DNA; stratum corneum penetration