Adverse effects of fullerenes on endothelial cells: Fullerenol C60(OH)24 induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro

We studied the effects of a C60 water suspension at 4 μg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1–100 μg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 μg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 ± 4% CD54+ cells vs. 19 ± 2 % CD54+ cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 ± 20% CD142+ cells vs 4 ± 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 ± 2% PS+ cells vs. 12 ± 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 ± 2% TUNEL+ cells at 100 μg/mL of C60(OH)24 vs. 4 ± 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60(OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium

Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics

Design and Function of a Dendrimer-Based Therapeutic Nanodevice Targeted to Tumor Cells Through the Folate Receptor

Purpose . We sought to develop nanoscale drug delivery materials that would allow targeted intracellular delivery while having an imaging capability for tracking uptake of the material. A complex nanodevice was designed and synthesized that targets tumor cells through the folate receptor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41493/1/11095_2004_Article_378868.pd

Biotargeted nanomedicines for cancer: six tenets before you begin

Biotargeted nanomedicines have captured the attention of academic and industrial scientists who have been motivated by the theoretical possibilities of the ‘magic bullet’ that was first conceptualized by Paul Ehrlich at the beginning of the 20th century. The Biotargeting Working Group, consisting of more than 50 pharmaceutical scientists, engineers, biologists and clinicians, has been formed as part of the National Cancer Institute’s Alliance for Nanotechnology in Cancer to harness collective wisdom in order to tackle conceptual and practical challenges in developing biotargeted nanomedicines for cancer. In modern science and medicine, it is impossible for any individual to be an expert in every aspect of biology, chemistry, materials science, pharmaceutics, toxicology, chemical engineering, imaging, physiology, oncology and regulatory affairs. Drawing on the expertise of leaders from each of these disciplines, this commentary highlights six tenets of biotargeted cancer nanomedicines in order to enable the translation of basic science into clinical practice

Assessing the barriers to image‐guided drug delivery

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102084/1/wnan1247.pd

Best Practices in Cancer Nanotechnology: Perspective from NCI Nanotechnology Alliance

Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities which are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems which could not be effectively solved in the past and include overcoming formulation issues, multi-drug-resistance phenomenon and penetrating cellular barriers that may limit device accessibility to intended targets such as the blood-brain-barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise towards new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics

Analysis of Fullerene-Based Nanomaterial in Serum Matrix by CE

With the increasing interest in using nanoparticles as vehicles for drug delivery and image contrast agents, there is a need to develop assays for their detection and quantitation in complex matrices to facilitate monitoring their biodistribution. In this study, we developed a CE approach for the analysis of two nanoparticles: carboxyfullerene (C3) and dendrofullerene (DF1) in both standard solutions and a serum matrix. These highly soluble, charged C(60) derivatives were characterized by CZE using either a bare or dynamically coated fused-silica capillaries. The resolution of both nanoparticles was slightly lower with the coated capillary; however, their migration times were faster. While separation of the DF1 nanoparticles using MEKC resulted in a greater number of observable peaks, the peak profile of C3 was basically unchanged regardless of whether SDS micelles were added to the running buffers or not. The MEKC and/or CZE assays were then used to quantitate the C3 and DF1 nanoparticles in spiked human serum samples. The quantitation of the nanoparticles was linear from 0-500 microg/mL with detection limits ranging from 0.5 to 6 microg/mL