Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multimorbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age.

Polymer-functionalized carbon nanotubes hold great promise for their use in environmental and biomedical applications. In this work, polyethyleneimine (PEI) was covalently bonded to acid-treated multiwalled carbon nanotubes (MWCNTs) through amide bond formation. The amine groups of PEI on the surface of MWCNTs were then reacted with acetic anhydride or succinic anhydride to form MWCNTs with neutral or negative surface charges, respectively. The structural transformation, surface potential, and morphology of the functionalized MWCNTs were characterized by nuclear magnetic resonance, thermogravimetric analysis, zeta potential, and transmission electron microscopy. The functionalized MWCNTs are water-soluble and stable. In vitro cytotoxicity assays using both FRO cells (a human thyroid cancer cell line) and KB cells (a human epithelial carcinoma cell line) reveal that the biocompatibility of these functionalized MWCNTs is largely dependent on their surface potential. Neutral and negatively charged MWCNTs are nontoxic to both cell lines at a concentration up to 100 µg/mL, whereas positively charged MWCNTs are toxic to FRO cells at 10 µg/mL. The results of this study demonstrate that PEI-modified MWCNTs can be chemically modified to alter their surface charges and cytotoxicity, thereby significantly improving the biocompatibility of the materials for a variety of biomedical applications.

Carbon nanotubes hold great promise for their use as a platform in nanomedicine, especially in drug delivery, medical imaging, and cancer targeting and therapeutics. Herein, we present a facile approach to modifying carbon nanotubes with multifunctional poly(amidoamine) (PAMAM) dendrimers for cancer cell targeting and imaging. In this approach, fluorescein isothiocyanate (FI)- and folic acid (FA)-modified amine-terminated generation 5 (G5) PAMAM dendrimers (G5·NH(2)-FI-FA) were covalently linked to acid-treated multiwalled carbon nanotubes (MWCNTs), followed by acetylation of the remaining primary amine groups of the dendrimers. The resulting MWCNT/G5.NHAc-FI-FA composites are water-dispersible, stable, and biocompatible. In vitro flow cytometry and confocal microscopy data show that the formed MWCNT/G5·NHAc-FI-FA composites can specifically target to cancer cells overexpressing high-affinity folic acid receptors. The results of this study suggest that, through modification with multifunctional dendrimers, complex carbon nanotube-based materials can be fabricated, thereby providing many possibilities for various applications in biomedical sensing, diagnosis, and therapeutics.

We report the complexation of a potential anticancer agent 2-methoxyestradiol (2-ME) with generation 5 (G5) poly(amidoamine) dendrimers having different surface functional groups for therapeutic applications. The complexation experiment shows that approximately 6–8 drug molecules can be complexed with one dendrimer molecule regardless the type of the dendrimer terminal groups. The bioactivity of 2-ME complexed with dendrimers was found to be significantly dependent on the surface charge of G5 dendrimers. In vitro cell biological assays show that amine, hydroxyl, and acetamide-terminated G5 dendrimers with positive, slightly positive, and close to neutral surface charges, respectively are able to deliver 2-ME to inhibit cancer cell growth. In contrast, 2-ME complexed with carboxyl-terminated G5 dendrimers with negative surface charges does not show its inherent bioactivity. Further molecular dynamics simulation studies show that the compact structure of carboxylated G5 dendrimers complexed with 2-ME does not allow the release of the drug molecules even at a pH of 5.0, which is the typical pH value in lysosome. Our findings indicate that the surface modification of dendrimers with different charges is crucial for the development of formulations of various anticancer drugs for therapeutic applications.

We develop a facile approach to fabricating multifunctional dendrimer-stabilized gold nanoparticles (Au DSNPs) for cancer cell targeting and imaging. In this work, amine-terminated generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers pre-functionalized with folic acid (FA) and fluorescein isothiocyanate (FI) are complexed with Au(III) ions, followed by acetylation of the amine groups on the dendrimer surfaces. This one-step process leads to the spontaneous formation of 6 nm-sized Au nanoparticles stabilized by multifunctional dendrimers bearing both targeting and imaging functionalities. The multifunctional Au DSNPs are characterized by UV-Vis spectrometry, 1 H NMR, and transmission electron microscopy (TEM). The formed Au DSNPs are water-soluble, stable, and biocompatible. Combined flow cytometry, confocal microscopy, silver staining, and inductively coupled plasma-mass spectrometry (ICP-MS) analyses show that the FAand FI-functionalized Au DSNPs can specifically target to cancer cells expressing high-affinity FA receptors in vitro. This approach to functionalizing Au DSNPs may be extended to other targeting molecules, providing a unique nanoplatform for targeting and imaging of a variety of biological systems.

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A facile approach has been developed to encapsulate submicrometer-sized drug crystals into polymer multilayer capsules produced by sequential deposition of polymers onto the drug particle surfaces. 2-Methoxyestradiol (2-ME) is a hydrophobic metabolite of 17-beta estradiol, which has been demonstrated as a potential anticancer agent. It was selected as a model drug and was formulated into submicrometer-sized particles through fine milling followed by intense sonication in the presence of dipalmitoyl-dl-(R)-phosphatidylcholine (DPPC). The reserved positive charges on the 2-ME crystal surface by DPPC enhanced the water solubility of the particles and subsequent self-assembly of dextran sulfate (DS) and dextran (DN) multilayers through hydrogen bonding and physical adsorption. Upon the exposure of the drug capsules to ethanol, hollow DS/DN multilayer polymer shells can be formed. The encapsulation process and hollow polymer multilayer shell formation were confirmed by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM), while the surface morphology of the formed drug capsules was investigated using scanning electron microscopy (SEM). In vitro studies show that the inhibitory effect of the formed 2-ME capsules is the same as that of the conventional formulation of 2-ME in a concentrated ethanol solution, as demonstrated by dramatic changes in cell morphology and significantly decreased viability of target cells. We also demonstrate that the change of the outermost layer of the drug capsules does not significantly influence its bioactivity. The presented strategy to encapsulate submicrometer-sized hydrophobic drug particles is expected to provide a general pathway to fabricate drug capsules for various biological applications.

As the number of clinical trials conducted in China increases, understanding Chinese attitudes toward clinical research is critical for designing effective and ethical studies. Two survey studies were conducted in 2012 and 2013 to compare patient attitudes toward clinical research and factors affecting research participation in the United States and urban and rural China. We surveyed 525 patients in 2012 (186 US, 186 urban, 153 rural China) and 690 patients in 2013 (412 US, 206 urban, 72 rural China). US patients were more likely to have no concerns regarding research participation than Chinese patients. Most common concerns of US patients were safety, privacy and confidentiality, and time required. Safety was a top concern for many Chinese. Chinese patients, particularly rural Chinese, were more concerned about the likelihood of self-benefit, and receiving free medical care and financial incentive had greater influence on their participation. Being informed of the freedom to choose whether to participate or to leave a study was less important to Chinese patients. Our study provides important insights into Chinese patients' attitudes toward clinical research and the need to educate them about their rights. These findings help in designing cross-cultural clinical studies that maximize enrollment while upholding Western ethical standards. Clin Trans Sci 2015; Volume 8: 123-131