Investigation of the Drug Binding Properties and Cytotoxicity of DNA-Capped Nanoparticles Designed as Delivery Vehicles for the Anticancer Agents Doxorubicin and Actinomycin D

Abstract

Oligonucleotide-functionalized gold nanoparticles (AuNP) were designed and synthesized to be delivery vehicles for the clinically used anticancer drugs doxorubicin (DOX) and actinomycin D (ActD). Each vehicle contains a tailorable number of DNA duplexes, each possessing three high-affinity sequences for the intercalation of either DOX or ActD, thus allowing for control of drug loading. Drug binding was evaluated by measuring changes to DNA melting temperature, T(m), hydrodynamic diameter, D(h), and surface plasmon resonance wavelength, λ(spr), with drug loading. These studies indicate that DOX intercalates at its high-affinity sequence bound at the AuNP, and that ActD exhibits relatively weaker binding to its preferred sequence. Agarose gel electrophoresis further confirmed drug binding and revealed that particle mobilities inversely correlate with D(h). The equilibrium binding constant, K, and dissociation rate constant, β, were determined by dialysis. Results indicate that the high negative electrostatic potential within the DNA shell of the particle significantly decreases β and enhances K for DOX but has little effect on K and β for ActD. The cytotoxicity of the vehicles was studied, with IC(50) = 5.6 ± 1.1 μM and 46.4 ± 9.3 nM for DOX-DNA-AuNP and IC(50) = 0.12 ± 0.07 μM and 0.76 ± 0.46 nM for ActD-DNA-AuNP, in terms of drug and particle concentrations, respectively.

Treatment of metastatic breast cancer by combination of chemotherapy and photothermal ablation using doxorubicin-loaded DNA wrapped gold nanorods

“…Additionally, the spherical gold nanoparticles without thermal property in the NIR region, were also capped with double stranded oligonucleotide for in vitro delivery of various chemotherapeutic drugs (i.e. doxorubicin (DOX), actinomycin D (ActD) or platinum) [32,33]. However, the application of GNRs for chemo and PTA dual modality therapy of metastatic cancers has not been reported yet.…”

Controlling DNA–nanoparticle serum interactions

“…Although there have been some in vitro studies on the degradation of DNA-functionalized nanoparticles in simplified biological medium [e.g., phosphate-buffered saline (PBS) spiked with nucleases or cell culture medium containing 10% (vol/vol) serum] (14)(15)(16)(17), there is little knowledge linking the physicochemical properties of DNA-coated and nucleotide-assembled nanoparticles to their biodegradation behavior in complex physiological fluids, such as whole blood or serum. Here, we provide systematic mapping of the serum breakdown rates and degradation processes as they relate to nanoparticle design parameters.…”

Liposome as nanocarrier: Site targeted delivery in lung cancer

“…So, they are particularly noticeable regarding this issue. Recently, an AuNP being used for patients of complex stage cancer has passed the phase I clinical trials as it constitutes surface bounded thiolated polyethylene glycol and recombinant human tumor necrosis factor alpha (rhTNF) [24]. Gold nanoparticles (AuNPs) due to their matchless plasmonic features and admirable biocompatibility are frequently betrothed as analytical as well as recuperative agents for cancer.…”