Tumor-Microenvironment-Activatable Nanoreactor Based on a Polyprodrug for Multimodal-Imaging-Medicated Enhanced Cancer Chemo/Phototherapy.

Anticancer nanomedicine-based multimodal imaging and synergistic therapy hold great promise in cancer diagnosis and therapy owing to their abilities to improve therapeutic efficiency and reduce unnecessary side effects, producing promising clinical prospects. Herein, we integrated chemotherapeutic drug camptothecin (CPT) and near-infrared-absorbing new indocyanine green (IR820) into a single system by charge interaction and obtained a tumor-microenvironment-activatable PCPTSS/IR820 nanoreactor to perform thermal/fluorescence/photoacoustic-imaging-guided chemotherapy and photothermal therapy simultaneously. Specifically, the generated PCPTSS/IR820 showed an excellent therapeutic agent loading content and size stability, and the trials in vitro and in vivo suggested that the smart PCPTSS/IR820 could deeply permeate into tumor tissues due to its suitable micellar size. Upon near-infrared laser irradiation, the nanoreactor further produced a terrific synergism of chemo-photo treatment for cancer therapy. Therefore, the PCPTSS/IR820 polyprodrug-based nanoreactor holds outstanding promise for multimodal imaging and combined dual therapy

Electroosmotic flow in a microchannel packed with microspheres

The electrokinetic (EK) micropump, which employs electroosmosis rather than hydrostatic pressure, is a rapidly emerging pumping technique to transport reagents and electrolytes through microchannel networks.DOCTOR OF PHILOSOPHY (MPE

A Microfluidic Impedance Cytometer on Printed Circuit Board for Low Cost Diagnosis

Coulter counters have been an important platform in biological cell detection and enumeration for several decades. Recently, the portable Coulter counter has attracted much attention due to its advantages in point of care diagnostics for on chip detection and enumeration of rare cells, such as circulating tumor cells. In this paper, we present a microfluidic cytometer based on Coulter principle on a SU-8 coated printed circuit board (PCB) substrate, which enables portable and low-cost diagnostics. The electrical current changes induced by the blockage of the microparticles in the sensing aperture of the Coulter counter are numerically analyzed and validated by experimental studies. Hela cells are used to test the performance of the proposed device. The proposed cytometer is built upon the cheap and widely available PCB substrate and show its great potential as a personalized healthcare monitor.ASTAR (Agency for Sci., Tech. and Research, S’pore

Porous prussian blue nanocubes as photothermal ablation agents for efficient cancer therapy

Nanomaterial-based photothermal agents have attracted great attention as near-infrared laserdriven ablation agents for tumor therapy. In this work, Prussian blue nanocubes with porous interior were synthesized via controlled chemical etching method and successfully applied for efficient photothermal ablation of tumor cells in vitro. Monodispersed porous Prussian blue nanocubes (115.4±4.7 nm) were produced through a controlled self-etching reaction in the presence of polyvinylpyrrolidone (PVP). Owing to the strong absorbance in near infrared (NIR) region, the resulted porous Prussian blue nanocubes could lead to more than 80% death of Hela cells after being treated with nanocubes of concentration as low as 100 μg mL−1. Compared to the traditional solid Prussian blue nanoparticles, these porous nanocubes can provide extra space for encapsulating anti-cancer drugs in their porous interior. It is anticipated that these porous Prussian blue nanocubes can be applied as an enabling platform to develop the next generation of multifunctional drug carrier for cancer treatments

3D numerical simulation of a Coulter counter array with analysis of electrokinetic forces

Coulter counters have played an important role in biological cell assays since their introduction decades ago. Several types of high throughput micro-Coulter counters based on lab-on-chip devices have been commercialized recently. In this paper, we propose a highly integrated micro-Coulter counter array working under low DC voltage. The real-time electrical current change, including the pulse amplitude and width, of the micro-Coulter counter with novel structure is systematically investigated numerically. The major types of forces exerted on the particle in the micro-Coulter counter, including hydrodynamic force and electrokinetic force are quantitatively analyzed. The simulation in this study shows the pulse profile, such as width and amplitude, is affected by both particle size and the flow condition. The special cases of multiple particle aggregation and cross-talk between neighboring channels are also considered for their effects on the electric current pulses. This simulation provides critical insight and guidance for developing next new generations of micro-Coulter counter

A microfluidic co-culture system to monitor tumor-stromal interactions on a chip

The living cells are arranged in a complex natural environment wherein they interact with extracellular matrix and other neighboring cells. Cell-cell interactions, especially those between distinct phenotypes, have attracted particular interest due to the significant physiological relevance they can reveal for both fundamental and applied biomedical research. To study cell-cell interactions, it is necessary to develop co-culture systems, where different cell types can be cultured within the same confined space. Although the current advancement in lab-on-a-chip technology has allowed the creation of in vitro models to mimic the complexity of in vivo environment, it is still rather challenging to create such co-culture systems for easy control of different colonies of cells. In this paper, we have demonstrated a straightforward method for the development of an on-chip co-culture system. It involves a series of steps to selectively change the surface property for discriminative cell seeding and to induce cellular interaction in a co-culture region. Bone marrow stromal cells (HS5) and a liver tumor cell line (HuH7) have been used to demonstrate this co-culture model. The cell migration and cellular interaction have been analyzed using microscopy and biochemical assays. This co-culture system could be used as a disease model to obtain biological insight of pathological progression, as well as a tool to evaluate the efficacy of different drugs for pharmaceutical studies.Published versio

Cellular Uptake Behaviors of Rigidity-Tunable Dendrimers

Understanding of the interaction between cells and nanoparticles (NPs) is critical. Despite numerous attempts to understand the effect of several parameters of NPs on their cellular uptake behaviors, such as size, shape, surface chemistry, etc., limited information is available regarding NP rigidity. Herein, we investigate the effect of rigidity on cellular uptake behaviors of NPs, using generation 5 poly(amidoamine) dendrimer as a model. By harnessing the abundant inner cavity, their rigidity could be effectively regulated by forming size-tunable gold NPs. The NPs thus formed were well characterized and displayed similar hydrodynamic size, surface potential, fluorescence intensity, and distinct rigidity (owing to differences in the size of the Au core). Flow cytometry analysis revealed a positive correlation between NP rigidity and cellular uptake of NPs. Confocal microscopic evaluation revealed that the entrapped gold NPs may affect the intracellular localization of the internalized dendrimers. The present findings can potentially guide the preparation of suitable NPs for biomedical applications