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.

Hexagonal Boron Nitride Functionalized with Au Nanoparticles—Properties and Potential Biological Applications

“…Gold nanoparticles (GNPs) are also considered to be an effective delivery platform. Fu et al [ 62 ] loaded Dox directly on GNPs by forming hydrazone (HDox-GNPs) or amide (SDox-GNPs) bonds. Their cytotoxicity and anticancer efficacy were evaluated using U87, HeLa, MCF-7 and A549 cell cultures.…”

“…SDox-GNPs exhibited much lower cytotoxicity against U87 cells. The difference in IC50 for SDox-GNPs was 2- to 18-fold higher compared to HDox-GNPs [ 62 ].…”

Metal–Organic Framework Nanocarriers for Drug Delivery in Biomedical Applications

“…Because of their extremely large surface area, highly porous structure, and easy chemical modification, MOFs have been extensively studied as ideal nanocarriers to load various drugs. For example, doxorubicin hydrochloride (DOX) represents one of the first-line chemotherapeutic drugs for breast cancer, ovarian cancer, and lymphoblastic leukemia [ 91 ]. Busulfan (Bu) is an amphiphilic antitumor drug widely used in chemotherapy for leukemia as an alternative to total-body irradiation [ 92 ].…”

AuNPs as an important inorganic nanoparticle applied in drug carrier systems

“…In the past several years, many pH-responsive drug carrier systems have been synthesized to initiate drug release in cancer cells due to this particular acidic environment of the tumour site [145]. For example, some acid-sensitive bonds such as amide bonds [146][147][148] and hydrazone bonds [149,150], are introduced into the AuNPs due to their cleavage in an acidic environment. Khutale…”