Multifunctional DNA-Gold Nanoparticles for Targeted Doxorubicin Delivery

Abstract

In this report we describe the synthesis, characterization, and cytotoxic properties of DNA-capped gold nanoparticles having attached folic acid (FA), a thermoresponsive polymer (p), and/or poly(ethylene glycol) (PEG) oligomers that could be used to deliver the anticancer drug doxorubicin (DOX) in chemotherapy. The FA-DNA oligomer used in the construction of the delivery vehicle was synthesized through the reaction of the isolated folic acid N-hydroxysuccinimide ester with the amino-DNA and the conjugated DNA product was purified using high performance liquid chromatography (HPLC). This approach ultimately allowed control of the amount of FA attached to the surface of the delivery vehicle. Cytotoxicity studies using SK-N-SH neuroblastoma cells with drug loaded delivery vehicles were carried out using a variety of exposure times (1-48 h) and recovery times (1-72 h), and in order to access the effects of varying amounts of attached FA, in culture media deficient in FA. DOX loaded delivery vehicles having 50% of the DNA strands with attached FA were more cytotoxic than when all of the strands contained FA. Since FA stimulates cell growth, the reduced cytotoxicity of vehicles fully covered with FA suggests that the stimulatory effects of FA can more than compensate for the cytotoxic effects of the drug on the cell population. While attachment of hexa-ethylene glycol PEG(18) to the surface of the delivery vehicle had no effect on cytotoxicity, 100% FA plus the thermoresponsive polymer resulted in IC50 = 0.48 ± 0.01 for an exposure time of 24 h and a recovery time of 1 h, which is an order of magnitude more cytotoxic than free DOX. Confocal microscopic studies using fluorescence detection showed that SK-N-SH neuroblastoma cells exposed to DOX-loaded vehicles have drug accumulation inside the cell and, in the case of vehicles with attached FA and thermoresponsive polymer, the drug appears more concentrated. Since the biological target of DOX is DNA, the latter observation is consistent with the high cytotoxicity of vehicles having both FA and the thermoresponsive polymer. The study highlights the potential of DNA-capped gold nanoparticles as delivery vehicles for doxorubicin in cancer chemotherapy.

The influence of the route of administration of gold nanoparticles on their tissue distribution and basic biochemical parameters: In vivo studies

“…Nanomedicine [4,5] uses gold nanoparticles for faster diagnosis (imaging) and treatment (drug delivery [4,6], tissue regeneration) as well as to develop new medical products. Nanoparticles are already marketed as novel tools for molecular imaging and drug delivery formulations [7][8][9].…”

“…Nanoparticles can be used as drug carriers for chemotherapeutics to deliver medication directly to the tumor while sparing healthy tissues. Nanocarriers present several advantages over conventional chemotherapy [9,14].…”

Biomedical Applications of DNA‐Conjugated Gold Nanoparticles

“…Alexander et al. designed DNA–AuNPs that have folic acid and a thermoresponsive polymer for loading with doxorubicin that increased cytotoxicity by an order of magnitude in comparison to free doxorubicin …”

ChemInform Abstract: Biomedical Applications of DNA‐Conjugated Gold Nanoparticles

“…[74] Alexander et al designedD NA-AuNPs that have folic acid and at hermoresponsive polymerf or loading withd oxorubicin that increased cytotoxicity by an order of magnitude in comparison to free doxorubicin. [109] In addition to loading anticancer drugs onto DNA-AuNPs, DNA-AuNPs can also serve as ag ene delivery system for hybridizing cancerc ell genes to knock down geneticf unctions. Bao et al used antisense DNA-AuNPs as ah ybrid platform to detect, target, and inhibit the expressiono famutated KRAS proto-oncogene in am urine gastric cancerm odel, with the designs hown in Figure 6.…”