Non-invasive transdermal delivery of chemotherapeutic molecules in vivo using superparamagnetic iron oxide nanoparticles

Cancer Nanotechnology

Lai F. Kok¹  Naomi C. Delic²  J. Guy Lyons³  Nicole Painter⁴  Nguyen T. H. Pham⁴  Brian S. Hawkett⁴  Byung J. Kim⁴  Vanisri Raviraj⁵  Binh T. T. Pham⁶  Stephen K. Jones⁷ 

[1] Department of Anatomical Pathology, Conde S. Januário Hospital, Macao, China;Dermatology, Sydney Medical School, and Centenary Institute, The University of Sydney, Sydney, NSW, Australia;Dermatology, Sydney Medical School, and Centenary Institute, The University of Sydney, Sydney, NSW, Australia;Dermatology, Cancer Services, Royal Prince Alfred Hospital, Sydney, Australia;Immune Imaging, Centenary Institute, The University of Sydney, Royal Prince Alfred Hospital, Bldg 93, Camperdown, NSW, Australia;Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney, Sydney, NSW, Australia;Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney, Sydney, NSW, Australia;Dermatology, Sydney Medical School, and Centenary Institute, The University of Sydney, Sydney, NSW, Australia;Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney, Sydney, NSW, Australia;Northern Clinical School and Kolling Institute, The University of Sydney, Sydney, NSW, Australia;Zeta Therapeutics Pty Ltd, and Sirtex Medical Ltd, Sydney, NSW, Australia;

关键词: Melanoma;    Transdermal;    Chemotherapy;    Nanoparticle;    Skin;    Doxorubicin;    5-Fluorouracil;   

DOI  :  10.1186/s12645-021-00079-7

来源: Springer

【 摘 要 】

BackgroundThe skin is both a target and a potential conduit for the delivery of drugs, but its cornified cell layer resists penetration by most molecules. This study investigated the potential of superparamagnetic iron oxide nanoparticles to facilitate the transdermal delivery of anticancer agents.ResultsChemotherapeutic cancer drugs were applied with or without nanoparticles to the skin of hairless mice, and their ability to penetrate the skin was assessed using fluorescence microscopy and tumor growth. Nanoparticles enhanced the penetration of the skin by doxorubicin and 5-fluorouracil as determined by fluorescence microscopy and growth retardation of experimental melanoma in immunocompetent, syngeneic mice. This drug enhancement did not require conjugation or encapsulation of the drugs by the nanoparticles—simple co-administration sufficed. Nanoparticles applied topically to melanomas increased the cytotoxicity and immune cell infiltration induced by co-administered 5-fluorouracil, and also reduced vascularization of the tumors independently of 5-fluorouracil.ConclusionCorrectly formulated superparamagnetic iron oxide nanoparticles can facilitate the chemotherapeutic effectiveness of cytotoxic drugs on skin tumors by both increasing their transdermal penetration and ameliorating host–tumor interactions. This enhancement of skin penetration occurs without the need for conjugation or encapsulation of the co-administered drugs, and so will likely be applicable to other drugs, also.

【 授权许可】

CC BY