Intranuclear drug delivery and effective in vivo cancer therapy via estradiol-PEG-appended multiwalled carbon nanotubes.

Cancer cell-selective, nuclear targeting is expected to enhance the therapeutic efficacy of a myriad of antineoplastic drugs, particularly those whose pharmacodynamic site of action is the nucleus. In this study, a steroid-macromolecular bioconjugate based on PEG-linked 17β-Estradiol (E2) was appended to intrinsically cell-penetrable multiwalled carbon nanotubes (MWCNTs) for intranuclear drug delivery and effective breast cancer treatment, both in vitro and in vivo. Taking Doxorubicin (DOX) as a model anticancer agent, we tried to elucidate how E2 appendage influences the cell internalization, intracellular trafficking, and antitumor efficacy of the supramolecularly complexed drug.

Augmented anticancer activity of a targeted, intracellularly activatable, theranostic nanomedicine based on fluorescent and radiolabeled, methotrexate-folic Acid-multiwalled carbon nanotube conjugate.

The present study reports the design, synthesis, and biological evaluation of a novel, intravenously injectable, theranostic prodrug based on multiwalled carbon nanotubes (MWCNTs) concomitantly decorated with a fluorochrome (Alexa-fluor, AF488/647), radionucleide (Technitium-99m), tumor-targeting module (folic acid, FA), and anticancer agent (methotrexate, MTX). Specifically, MTX was conjugated to MWCNTs via a serum-stable yet intracellularly hydrolyzable ester linkage to ensure minimum drug loss in circulation. Cell uptake studies corroborated the selective internalization of AF-FA-MTX-MWCNTs (1) by folate receptor (FR) positive human lung (A549) and breast (MCF 7) cancer cells through FR mediated endocytosis.

Surface chemistry dependent "switch" regulates the trafficking and therapeutic performance of drug-loaded carbon nanotubes.

The present study explores the possibility of exploiting surface functionality as one of the key regulators for modulating the intracellular trafficking and therapeutic performance of drug loaded carbon nanotubes (CNTs). In line with that approach, a series of biofunctionalized multiwalled carbon nanotubes (f-CNTs 1-6) decorated with various functional molecules including antifouling polymer (PEG), tumor recognition modules (folic acid/hyaluronic acid/estradiol), and fluorophores (rhodamine B isothiocyanate/Alexa Fluor) were synthesized. By loading different anticancer agents (methotrexate (MTX), doxorubicin (DOX), and paclitaxel (PTX)) onto each functionalized CNT preparation, we tried to elucidate how the surface functional molecules associated with each f-CNT influence their therapeutic potential.

Hyaluronate tethered, "smart" multiwalled carbon nanotubes for tumor-targeted delivery of doxorubicin.

The present study reports the optimized synthesis, physicochemical characterization, and biological evaluation of a novel, multiwalled carbon nanotube-hyaluronic acid (MWCNT-HA) conjugate, complexed with an anticancer agent, Doxorubicin (DOX) via π-π stacking interaction. The therapeutic conjugate was concomitantly labeled with a near-infrared fluorescent dye, Alexa-Flour-647 (AF-647), and radiotracer Technetium-99m ((99m)Tc) to track its whereabouts both in vitro and in vivo via optical and scintigraphic imaging techniques. Covalent functionalization of MWCNTs with HA facilitated their internalization into human lung adenocarcinoma, A549 cells via hyaluronan receptors (HR) mediated endocytosis.