Mesoporous silica-coated gold nanorods (Au@SiO(2)) are developed as a promising and versatile theranostic platform for cancer treatment. Intracellular localization of Au@SiO(2) is visualized through two-photon imaging. With doxorubicin hydrochloride loaded, Au@SiO(2)-DOX show two light-mediated therapeutic modes: low power density laser-triggered drug release for chemotherapy, and high power density laser-induced hyperthermia, which suggest the potential for in-vivo applications.

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External stimuli, such as ultrasound, magnetic field, and light, can be applied to activate in vivo tumor targeting. Herein, we fabricated polymer encapsulated gold nanorods to couple the photothermal properties of gold nanorods and the thermo- and pH-responsive properties of polymers in a single nanocomposite. The activation mechamism was thus transformed from heat to near-infrared (NIR) laser, which can be more easily controlled. Doxorubicin, a clinical anticancer drug, can be loaded into the nanocomposite through electrostatic interactions with high loading content up to 24%. The nanocomposite's accumulation in tumor post systematic administration can be significantly enhanced by NIR laser irradiation, providing a prerequisite for their therapeutic application which almost completely inhibited tumor growth and lung metastasis. Since laser can be manipulated very precisely and flexibly, the nanocomposite provides an ideally versatile platform to simultaneously deliver heat and anticancer drugs in a laser-activation mechanism with facile control of the area, time, and dosage. The NIR laser-induced targeted cancer thermo-chemotherapy without using targeting ligands represents a novel targeted anticancer strategy with facile control and practical efficacy.

We have observed that Au nanorods (NRs) have distinct effects on cell viability via killing cancer cells while posing negligible impact on normal cells and mesenchymal stem cells. Obvious differences in cellular uptake, intracellular trafficking, and susceptibility of lysosome to Au NRs by different types of cells resulted in selective accumulation of Au NRs in the mitochondria of cancer cells. Their long-term retention decreased mitochondrial membrane potential and increased reactive oxygen species level that enhances the likelihood of cell death. These findings thus provide guidance for the design of organelle-targeted nanomaterials in tumor therapy.

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Regarding the importance of the biological effects of nanomaterials, there is still limited knowledge about the binding structure and stability of the protein corona on nanomaterials and the subsequent impacts. Here we designed a hard serum albumin protein corona (BSA) on CTAB-coated gold nanorods (AuNRs) and captured the structure of protein adsorption using synchrotron radiation X-ray absorption spectroscopy, microbeam X-ray fluorescent spectroscopy, and circular dichroism in combination with molecular dynamics simulations. The protein adsorption is attributed to at least 12 Au-S bonds and the stable corona reduced the cytotoxicity of CTAB/AuNRs. These combined strategies using physical, chemical, and biological approaches will improve our understanding of the protective effects of protein coronas against the toxicity of nanomaterials. These findings have shed light on a new strategy for studying interactions between proteins and nanomaterials, and this information will help further guide the rational design of nanomaterials for safe and effective biomedical applications.

With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.

We investigated how surface chemistry influences the interaction between gold nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from them in a serum-free cell culture system. Our results showed that the AuNRs coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects in the cell membrane and induce cell death, mainly due to the unique bilayer structure of CTAB molecules on the surface of the rods rather than their charge. Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e. poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved biocompatibility towards cells. Thus, the present results indicate that the nature of surface molecules, especially their packing structures on the surface of AuNRs rather than surface charge, play a more crucial role in determining cytotoxicity. These findings about interfacial interactions could also explain the effects of internalized AuNRs on the structures or functions of organelles. This study will help understanding of the toxic nature of AuNRs and guide rational design of the surface chemistry of AuNRs for good biocompatibility in pharmaceutical therapy.