Coating mechanisms of single-walled carbon nanotube by linear polyether surfactants: insights from computer simulations

The noncovalent coating of carbon-based nanomaterials, such as carbon nanotubes, has important applications in nanotechnology and nanomedicine. The molecular modeling of this process can clarify its mechanism and provide a tool for the design of novel materials. In this paper, the coating mechanism of single-walled carbon nanotubes (SWCNT) in aqueous solutions by 1,2-dimethoxyethane oxide (DME), 1,2-dimethoxypropane oxide (DMP), poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) pentamers, and L64 triblock copolymer chains have been studied using molecular dynamics (MD) simulations. The results suggest a preferential binding to the SWCNT surface of the DMP molecules with respect to DME mainly driven by their difference in hydrophobicity. For the longer pentamers, it depends by the chain conformation. PPO isomers with radius of gyration larger than PEO pentamers bind more tightly than those with more compact conformation. In the case of the L64 triblock copolymer, the coating of the SWCNT surface produces a shell of PPO blocks with the PEO chains protruding into bulk water as expected from the so-called nonwrapping binding mechanism of SWCNT. In addition, the polymer coating, in qualitative agreement with experimental evidence on the poor capability of the L64 to disperse SWCNT, do not prevent the formation of CNT aggregates

An interlaboratory comparison on the characterization of a sub-micrometer polydisperse particle dispersion

The measurement of polydisperse protein aggregates and particles in biotherapeutics remains a challenge, especially for particles with diameters of ≈ 1 µm and below (sub-micrometer). This paper describes an interlaboratory comparison with the goal of assessing the measurement variability for the characterization of a sub-micrometer polydisperse particle dispersion composed of five sub-populations of poly(methyl methacrylate) (PMMA) and silica beads. The study included 20 participating laboratories from industry, academia, and government, and a variety of state-of-the-art particle-counting instruments. The received datasets were organized by instrument class to enable comparison of intralaboratory and interlaboratory performance. The main findings included high variability between datasets from different laboratories, with coefficients of variation from 13 % to 189 %. Intralaboratory variability was, on average, 37 % of the interlaboratory variability for an instrument class and particle sub-population. Drop-offs at either end of the size range and poor agreement on maximum counts of particle sub-populations were noted. The mean distributions from an instrument class, however, showed the size-coverage range for that class. The study shows that a poly-disperse sample can be used to assess performance capabilities of an instrument set-up (including hardware, software, and user settings) and provides guidance for the development of polydisperse reference materials.Drug Delivery Technolog

Targeted drug delivery using carbon nanotubes for cancer therapeutics

Even though progress has been made in decreasing cancer mortality, cancer is still one of the major causes of death in US. Chemotherapy the most common cancer treatment has severe and lethal side effects. This thesis reports, the use of single walled carbon nanotubes (SWNT) as novel one-dimensional nanomaterials for cancer treatment and detection. Advantage of SWNTs is, they are capable of delivering therapeutic agents and imaging agents, having the ability to overcome various biological barriers and to localize into the target tissue. The major focus of this PhD thesis is the development of carbon nanotube based targeted cancer drug delivery systems than can be utilized in nanomedicine-based therapy protocols to improve patient outcome. This thesis has five chapters beginning with general background and significance of this work in chapter one. For the first time Head and neck squamous cell carcinoma cells were targeted using epidermal growth factor (EGF) guided SWNTs conjugated to quantum dots for visualization or with cisplatin for killing the cancer cells in vitro/in vivo. EGF-complexed SWNTs towards improved site specific therapeutic targeting of in vivo and in vitro cancer models is clearly demonstrated in the second chapter. Chapter 3 describes the first example of imaging the distribution of drug molecules using scanning transmission electron microscopy for atomic scale visualization and quantitation of single cisplatin molecules attached SWNTs designed for targeted drug-delivery. Chapter 4 demonstrates the distribution and clearance of PEG wrapped SWNT cancer drug delivery vehicles in mice. The successful outcome of cancer chemotherapy often depends on the early detection of the cancer lesion. Chapter 5 describes amperometric enzyme-linked immunoassays for Platelet Factor 4 built on vertically aligned arrays SWNTs forests on pyrolytic graphite surface. The optimized SWNT forests setup was extended to detect multiple biomarkers concurrently in a single serum sample. Horseradish peroxidase was used as label on detection antibodies in the sandwich immunoassay. This chapter demonstrated reproducible and accurate electrochemical detection of PF-4 protein cancer biomarker in serum using a common procedure with SWNT-based immunoarrays. These studies suggest the excellent potential for array fabrication leading to real time multiplexed cancer biomarker detection for point-of-care diagnostic assays

Nano Delivers Big: Designing Molecular Missiles for Cancer Therapeutics

Current first-line treatments for most cancers feature a short-list of highly potent and often target-blind interventions, including chemotherapy, radiation, and surgical excision. These treatments wreak considerable havoc upon non-cancerous tissue and organs, resulting in deleterious and sometimes fatal side effects for the patient. In response, this past decade has witnessed the robust emergence of nanoparticles and, more relevantly, nanoparticle drug delivery systems (DDS), widely touted as the panacea of cancer therapeutics. While not a cure, nanoparticle DDS can successfully negotiate the clinical payoff between drug dosage and side effects by encompassing target-specific drug delivery strategies. The expanding library of nanoparticles includes lipoproteins, liposomes, dendrimers, polymers, metal and metal oxide nano-spheres and -rods, and carbon nanotubes, so do the modes of delivery. Importantly, however, the pharmaco-dynamics and –kinetics of these nano-complexes remain an urgent issue and a serious bottleneck in the transition from bench to bedside. This review addresses the rise of nanoparticle DDS platforms for cancer and explores concepts of gene/drug delivery and cytotoxicity in pre-clinical and clinical contexts

Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles

National Basic Research Program of China (973 Program) [2013CB733802, 2010CB934602]; National Science Foundation of China (NSFC) [81101101, 81201086, 81201129, 81201190, 51273165, 51172005, 81028009]; Chinese Academy of Sciences Professorship for Senior International Scientists [2011T2J06]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); China Scholarship CouncilMagnetic nanoparticles have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles (SIONPs) loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging (MRI) and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin (HSA) method to modify hollow iron oxide nanoparticles (HIONPs) and encapsuated doxorubicin (DOX) within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8-ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T (2) MRI signal intensity and can be used as a MRI contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells