We report dual-functional hollow gold nanospheres (HAuNS, ∼40-nm diameter) capable of mediating both photothermal ablation of cancer cells and drug release upon near-infrared (NIR) light irradiation. As high as 63% DOX by weight (∼1.7 μg DOX/μg Au) could be loaded to polyethylene glycol (PEG)-coated HAuNS since DOX was coated to both the outer and the inner surfaces of HAuNS. Irradiation with NIR laser induced photothermal conversion, which triggered rapid DOX release from DOX-loaded HAuNS. The release of DOX was also pH-dependent, with more DOX released in aqueous solution at lower pH. Significantly greater cell killing was observed when MDA-MB-231 cells incubated with DOX-loaded HAuNS were irradiated with NIR light, attributable to both HAuNS-mediated photothermal ablation and cytotoxicity of released free DOX. Keywordshollow gold nanospheres; doxorubicin; triggered release; near-infrared light; antitumor activity Nanocarriers have been designed as a novel platform for the delivery of therapeutic agents. Among the drug carriers reported, liposomes and lipid nanospheres 1 have come onto the market. Polymeric drugs are currently in clinical trials. 2, 3 All of these are organic nanoparticles consisting of lipids and/or synthetic polymers. Whereas rapid progress has been made in the development of drug delivery systems using organic nanoparticles, relatively less progress has been made in the development of inorganic nanoparticle-based drug delivery systems. However, recent progress in the field of nanotechnology and nanofabrication has led to the identification of various inorganic nanoparticles as attractive vehicles for drug delivery, such as iron oxide nanoparticles for delivery of anticancer drugs (mitoxantrone 4 and doxorubicin 5 ), carbon nanohorns for delivery of dexamethasone (an anti-inflammatory agent) 6 and cisplatin (an anticancer agent), 7 carbon nanotubes for delivery of anticancer drugs (paclitaxel, 8 platinum, 9, 10 and doxorubicin 11 ), and gold nanoparticles. These inorganic nanoparticles have several advantages as drug carriers. First, they are easy to prepare with a defined size. More interestingly, they often exhibit multiple functions useful in medicine-for example, serving as exothermic reactors and contrast agents-whereas organic nanoparticles such as liposomes and polymer nanospheres serve only as drug reservoirs.

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Herein, three new glycopolymers have been synthesized via "click polymerization" to promote nucleic acid delivery in the presence of biological media containing serum. These structures were designed to contain a trehalose moiety to promote biocompatibility, water solubility, and stability against aggregation, amide-triazole groups to enhance DNA binding affinity, and an oligoamine unit to facilitate DNA encapsulation, phosphate neutralization, and interactions with cell surfaces. A 2,3,4,2',3',4'-hexa-O-acetyl-6,6'-diazido-6,6'-dideoxy-D-trehalose (4) monomer was polymerized via copper(I)-catalyzed azide-alkyne cycloaddition with a series of dialkyne-amide comonomers that contain either one, two, or three Boc-protected secondary amines (7a, 7b, or 7c, respectively). After deprotection, three water-soluble polycations (9a, 9b, or 9c) were obtained with similar degrees of polymerization (n = 56-61) to elucidate the role of amine number on nucleic acid binding, complex formation, stability, and cellular delivery. Gel electrophoresis and ethidium bromide experiments showed that 9a-9c associated with plasmid DNA (pDNA) and formed complexes (polyplexes) at N/P ratios dependent on the amine number. TEM experiments revealed that 9a-9c polyplexes were small (50-120 nm) and had morphologies (spherical and rodlike) associated with the polymer chain stiffness. Dynamic light scattering studies in the presence of media containing serum demonstrated that 9c polyplexes had a low degree of flocculation, whereas 9a and 9b polyplexesd aggregate rapidly. Further biological studies revealed that these structures were biocompatible and deliver pDNA into HeLa cells. Particularly, 9c polyplexes promoted high delivery efficacy and gene expression profiles in the presence of serum.

The mechanism of the hyperlipidaemia is unclear but it may be related to the glucose intolerance with hyperinsulinaemia which is found in uraemia. In view of the risk of premature atherosclerosis, plasma lipid concentrations should be monitored in children with chronic renal failure and attempts made to ameliorate hyperlipidaemia with appropriate dietary manipulations.

The efficacy of cancer drugs is often limited because only a small fraction of the administered dose accumulates in tumors. Here we report an injectable nanoparticle generator (iNPG) that overcomes multiple biological barriers to cancer drug delivery. The iNPG is a discoidal micrometer-sized particle that can be loaded with chemotherapeutics. We conjugate doxorubicin to poly(L-glutamic acid) via a pH-sensitive cleavable linker, and load the polymeric drug (pDox) into iNPG to assemble iNPG-pDox. Once released from iNPG, pDox spontaneously forms nanometer-sized particles in aqueous solution. Intravenously injected iNPG-pDox accumulates at tumors due to natural tropism and enhanced vascular dynamics and releases pDox nanoparticles that are internalized by tumor cells. Intracellularly, pDox nanoparticles are transported to the perinuclear region and cleaved into Dox, thereby avoiding excretion by drug efflux pumps. Compared to its individual components or current therapeutic formulations, iNPG-pDox shows enhanced efficacy in MDA-MB-231 and 4T1 mouse models of metastatic breast cancer, including functional cures in 40–50% of treated mice.