Standalone Lab-on-a-Chip Systems toward the Evaluation of Therapeutic Biomaterials in Individualized Disease Treatment

As each tumor is unique, treatments should be individualized in terms of their drug formulation and time dependent dosing. In vitro lab-on-a-chip (LOC) drug testing is a viable avenue to individualize treatments. A drug testing platform in the form of a customizable standalone LOC system is proposed for treatment individualization in vitro. The platform was used to individualize the treatment of pancreatic cancer by using PANC-1 and MIA PaCa-2 cell lines cultured on-chip. Using on-chip drug uptake, growth, and migration inhibition assays, the therapeutic effect of various treatment combinations was analyzed. Thereafter, optimized treatments were devised for each cell line. The individualized dosage for MIA PaCa-2 cell line was found to be between 0.05–0.1 μg/μL of doxorubicin (DOX), where the greatest growth and migration inhibition effects were observed. As the PANC-1 cell line showed resistance to DOX only formulations, a multidrug approach was used for individualized treatment. Compared to the DOX only formulations, the individualized treatment produced the same degree of migration inhibition but with 5–10 times lower concentration of DOX, potentially minimizing the side-effects of the treatment. Furthermore, the individualized treatment had an average of 672.4% higher rate of growth inhibition. Finally, a preliminary study showed how a tested formulation from the LOC system can be translated for use by employing a nanoparticle system for controlled delivery, producing similar therapeutic effects. The use of such systems in clinical practice could potentially revolutionize treatment formulation by maximizing the therapeutic effects of existing treatments while minimizing their potential side effects through individualization of treatment

MOESM1 of Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice

Additional file 1. Results from flow cytometry analysis of QDs uptake, ICP-MS analysis of Se element in major organs, the phagocytic assay of peritoneal macrophages, and MTT assay of macrophages treated with different types of QDs are presented

Two-Dimensional Transition Metal Dichalcogenide Enhanced Phase-Sensitive Plasmonic Biosensors: Theoretical Insight

Atomically thin transition metal dichalcogenide nanomaterials have shown superior optical and electronic properties in the two-dimensional (2D) scale. They are considered as promising alternative materials to graphene. Here, we have precisely engineered a plasmonic sensing substrate with four types of two-dimensional transition metal dichalcogenide nanomaterial to achieve significant phase sensitivity improvement. Phase modulation is currently the most sensitive interrogation method among all the plasmonic detection approaches. The tuning of the substrate thickness in an atomic scale with a step less than 1 nm allows the efficient modulation of phase signals. More importantly, the optical absorption rate for each of these nanomaterials is different and can be tuned by changing the number of 2D layers, where perfect absorption and interrogation of the plasmonic signal can be obtained. Through systematically optimizing the parameters of the transition metal dichalcogenide structured plasmonic substrate, we can balance the optical absorption efficiencies and the electron losses at the plasmonic resonance condition. All of the calculations were based on the transfer matrix method and Fresnel equations. A very low minimum reflectivity of 3.2560 × 10^–8 was demonstrated with an excitation wavelength of 1024 nm, showing a complete transfer (∼100%) of the light energy into the plasmon resonance energy. The ultradark singularity at the resonance dip leads to an ultrahigh plasmonic sensitivity of 1.1 × 10⁷ deg/RIU, which is 3 orders of magnitude higher than those with bare metallic sensing substrates used in commercial plasmonic sensors. The resolution is also improved by at least 3 orders of magnitude compared with conventional substrates

Assessing Clinical Prospects of Silicon Quantum Dots: Studies in Mice and Monkeys

Silicon nanocrystals can provide the outstanding imaging capabilities of toxic heavy-metal-based quantum dots without employing heavy metals and have potential for rapid progression to the clinic. Understanding the toxicity of silicon quantum dots (SiQDs) is essential to realizing this potential. However, existing studies of SiQD biocompatibility are limited, with no systematic progression from small-animal to large-animal studies that are more clinically relevant. Here, we test the response of both mice and monkeys to high intravenous doses of a nanoconstruct created using only SiQDs and FDA-approved materials. We show that (1) neither mice nor monkeys show overt signs of toxicity reflected in their behavior, body mass, or blood chemistry, even at a dose of 200 mg/kg. (2) This formulation did not biodegrade as expected. Elevated levels of silicon were present in the liver and spleen of mice three months post-treatment. (3) Histopathology three months after treatment showed adverse effects of the nanoformulation in the livers of mice, but showed no such effects in monkeys. This investigation reveals that the systemic reactions of the two animal models may have some differences and there are no signs of toxicity clearly attributable to silicon quantum dots