title: Comparison of Two Approaches for the Attachment of a Drug to Gold Nanoparticles and Their Anticancer Activities.
abstract: Drug attachment is important in drug delivery for cancer chemotherapy. The elucidation of the release mechanism and biological behavior of a drug is essential for the design of delivery systems. Here, we used a hydrazone bond or an amide bond to attach an anticancer drug, doxorubicin (Dox), to gold nanoparticles (GNPs) and compared the effects of the chemical bond on the anticancer activities of the resulting Dox-GNPs. The drug release efficiency, cytotoxicity, subcellular distribution, and cell apoptosis of hydrazone-linked HDox-GNPs and amide-linked SDox-GNPs were evaluated in several cancer cells. HDox-GNPs exhibited greater potency for drug delivery via triggered release comediated by acidic pH and glutathione (GSH) than SDox-GNPs triggered by GSH alone. Dox released from HDox-GNPs was released in lysosomes and exerted its drug activity by entering the nuclei. Dox from SDox-GNPs was mainly localized in lysosomes, significantly reducing its efficacy against cancer cells. In addition, in vivo studies in tumor-bearing mice demonstrated that HDox-GNPs and SDox-GNPs both accumulate in tumor tissue. However, only HDox-GNPs enhanced inhibition of subcutaneous tumor growth. This study demonstrates that HDox-GNPs display significant advantages in drug release and antitumor efficacy.
authors: College of Chemistry and Molecular Science, The Institute for Advanced Studies, Wuhan University , Wuhan 430072, China.
authors: Yingjie
authors: Y
authors: Fu
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Qishuai
authors: Q
authors: Feng
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Yifan
authors: Y
authors: Chen
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Yajing
authors: Y
authors: Shen
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Qihang
authors: Q
authors: Su
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Yinglei
authors: Y
authors: Zhang
authors: College of Chemistry and Molecular Science, The Institute for Advanced Studies, Wuhan University , Wuhan 430072, China.
authors: Xiang
authors: X
authors: Zhou
authors: Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine , Shanghai 200029, China.
authors: Yu
authors: Y
authors: Cheng
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry* / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D006046:Gold / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D006046:Gold; D004317:Doxorubicin
keywords: anticancer activity; doxorubicin; drug delivery; gold nanoparticle