Combination therapy, or the use of multiple drugs, has been proven to be effective for complex diseases, but the differences in chemical properties and pharmacokinetics can be challenging in term of the loading, delivering, and releasing multiple drugs. Here we demonstrate that we can load and selectively release two different DNA oligonucleotides from two different gold nanorods. DNA was loaded on the nanorods via thiol conjugation. Selective releases were induced by selective melting of gold nanorods via ultrafast laser irradiation at the nanorods' longitudinal surface plasmon resonance peaks. Excitation at one wavelength could selectively melt one type of gold nanorods and selectively release one type

Customizable ligand exchange of gold nanorods (NRs) is described. NRs are synthesized with the cationic surfactant cetyltrimethylammonium bromide (CTAB) which is exchanged with thiolated ligands that enable suspension in buffer. Exchange is achieved by a two phase extraction. First, CTAB is removed from the NR-CTAB by extracting the NRs into an organic phase via the ligand dodecanethiol (DDT). The NR-DDT are then extracted into an aqueous phase by mercaptocarboxylic acids (MCA), HS-(CH 2)n -COOH (n = 5, 10, and 15). Ligands can be further customized to thiolated poly(ethylene glycol), PEG MW (MW = 356, 5000, and 1000). Ligand-exchanged NRs (NR-MCA and NR-PEG(MW)) are stable in buffer, do not aggregate, and do not change size upon ligand exchange. They can be run in agarose gel electrophoresis with narrow bands, indicating uniform charge distribution and enabling quantitative analysis. DNA functionalization of NR-MCA is straightforward and quantifiable, with minimal nonspecific adsorption.

Gold nanorods (GNRs) stabilized with cetyltrimethylammonium bromide (CTAB) and GNR functionalized via a ligand exchange method with either thiolated polyethylene glycol (PEG(5000)) or mercaptohexadecanoic acid (MHDA) were investigated for their stability in biological media and subsequent toxicological effects to HaCaT cells. GNR-PEG and GNR-MHDA exhibited minimal effects on cell proliferation, whereas GNR-CTAB reduced cell proliferation significantly due to the inherent toxicity of the cationic surfactant to cells. Cell uptake studies indicated relatively low uptake for GNR-PEG and high uptake for GNR-MHDA. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that GNR-PEG induced less significant and unique changes in the transcription levels of 84 genes related to stress and toxicity compared to GNR-MHDA. The results demonstrate that, although cell proliferation was not affected by both particles, there is a significant difference in gene expression in GNR-MHDA exposed cells, suggesting long-term implications for chronic exposure.

We report a morphological study of the encapsulation of 12-nm Fe3O4 nanoparticles (NPs) in large unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC). Preparation was done by reverse-phase evaporation. Phase behavior of the NP-lipid system was studied so that the loading of NPs in vesicles could be maximized. Increasing NP concentration significantly affects the resulting lipid morphology in a manner similar to increasing lipid concentration. Optimal production of high-density NP-loaded vesicles (HNLVs) requires temperatures of 50 degrees C, higher than the main phase transition (Tm) of DPPC. The formation of fully enclosed HNLVs requires incubation times of at least hours.

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