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.
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