Performance of Doxorubicin-Conjugated Gold Nanoparticles: Regulation of Drug Location

Abstract

Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHN═Dox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 μg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents.

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

“…Cui et al designed PEG-modified GNPs to deliver DOX, and the results showed that the nanomedicine had higher solubility, stability, and dispersibility. 116 In addition, GNPs have a unique two-step drug release, respectively, in the lysosome and in the cytoplasm, thus a controlled and sustained release of the drug can be achieved which in turn can improve the antitumor effect of the drugs. 116 Hamzawy et al designed to use GNPs and liposome-embedded GNPs (LGNPs) to deliver temozolomide (TMZ).…”

“…116 In addition, GNPs have a unique two-step drug release, respectively, in the lysosome and in the cytoplasm, thus a controlled and sustained release of the drug can be achieved which in turn can improve the antitumor effect of the drugs. 116 Hamzawy et al designed to use GNPs and liposome-embedded GNPs (LGNPs) to deliver temozolomide (TMZ). TMZ-loaded GNPs (TGNPs) and TMZ-loaded LGNPs (LTGNPs) were used against urethane-induced lung cancer in BALB/c mice through intratracheal inhalation.…”

Iron–gold alloy nanoparticles serve as a cornerstone in hyperthermia-mediated controlled drug release for cancer therapy

“…Furthermore, while the nonspecific distribution of chemotherapy drugs in vivo, accompanied with rapid clearance, significantly limits the drug potency, administering drugs at higher dosage is undesirable as it often poses a serious cytotoxic threat. To overcome the conventional drawbacks of chemotherapy, a variety of drug carriers such as polymeric nanoparticles, 19 polymeric micelles, 20 dendrimers, 21 liposomes, 22 magnetic nanoparticles (MNPs), 23 and silica 24 or gold nanoparticles 25 have been used to achieve targeted drug delivery (TDD).…”

Bacterial Template Synthesis of Multifunctional Nanospindles for Glutathione Detection and Enhanced Cancer-Specific Chemo-Chemodynamic Therapy

“…However, its short systemic circulation time, undesirable biodistribution, and nonspecific toxicities to cancer/normal cells lead to not only relatively low anticancer efficacy but also severe side effects [4,5]. To address these issues, various nanocarriers such as liposomes [6], micelles [7], dendrimers [8], metal-organic frameworks (MOFs) [9], carbon nanomaterials [10], and gold nanomaterials [11,12] have been designed for the efficient delivery of DOX to cancer cells. Among them, conventional nanocarriers which tend to release the encapsulated DOX molecules passively cannot realize controllable drug release and fail to achieve satisfactory therapeutic efficacy [13].…”