σ-Holes in Iodonium Ylides: Halogen-Bond Activation of Carboxylic Acids, Phenols and Thiophenols May Enable Their X-H Insertion Reactions.

The first systematic evaluation of the electrostatic potential energy maps of iodonium ylides was conducted. We determined that they possess two σ-holes of differing electron deficiencies, with the more electropositive σ-hole located opposite the dative I-C bond to the ß-dicarbonyl motif, and the lesser electropositive σ-hole located opposite the iodoarene C-I bond. We also conducted the first systematic evaluation of carboxylic acids, phenols and thiophenols in the O/S-alkylation reaction of iodonium ylides. While carboxylic acids and thiophenols were found to be generally viable, only phenols possessing electron-withdrawing substituents were effective. This high-yielding and highly chemoselective reaction is believed to involve halogen-bond activation of heteroatoms, and nicely complements existing diazo-based methods for alkylation of acidic functional groups.

Microchips for detection of exfoliated tumor cells in urine for identification of bladder cancer.

Bladder cancer (BC) is a common malignancy, and it accounts for one of the highest management costs among urogenital cancers. As a non-invasive method, urine cytology plays an important role in the detection of exfoliated tumor cells (ETCs) for early diagnosis of BC. However, urine cytology suffers from its low sensitivity and reliance on microscopic examination. To address this issue, an integrated filtration device was developed with a pore size of 5 µm that isolated and enriched ETCs from discarded urine samples, and then quantified ETCs using a microchip ELISA method. The results revealed that the number of urinary ETCs from BC patients (n = 35) was obviously higher than the number of ETCs from healthy donors (n = 20). The ROC curve showed that the integrated filtration microfluidic device had a sensitivity of 77.1% when the specificity was set at 90% in identifying BC patients. Thus, the integrated filtration device holds great potential for the screening of BC or the follow-up analysis of treatment efficacy in point-of-care (POC) settings.

Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing.

Cancer poses a great health threat to both developed and developing countries, and anti-cancer drugs are of important interest for improved clinical outcomes. Although tumor-on-a-chip technologies offer a feasible approach to screening drug toxicity, their capability to mimic the native tumor microenvironment (TME) is still limited. For better mimicry of the TME, we developed a biomimetic three-dimensional (3D) liver tumor-on-a-chip with the integration of essential components derived from decellularized liver matrix (DLM) with gelatin methacryloyl (GelMA) in a microfluidics-based 3D dynamic cell culture system. The biomimetic liver tumor-on-a-chip based on the integration of DLM components with GelMA, as opposed to GelMA only, had an increased capability to maintain cell viability and to enhance hepatocyte functions under flow conditions. The improved performance of the DLM-GelMA-based tumor-on-a-chip may be attributed to the provision of biochemical factors (e.g., growth factors), the preservation of scaffold proteins, and the reestablishment of biophysical cues (e.g., stiffness and shear stress) for better recapitulation of the 3D liver TME. Furthermore, this DLM-GelMA-based tumor-on-a-chip exhibited linear dose-dependent drug responses to the toxicity of acetaminophen and sorafenib. Taken together, our study demonstrates that the DLM-GelMA-based biomimetic liver tumor-on-a-chip better mimics the in vivo TME and holds great promise for a breadth of pathological and pharmacological studies.

Tumor-on-a-chip platforms for assessing nanoparticle-based cancer therapy.

Cancer has become the most prevalent cause of deaths, placing a huge economic and healthcare burden worldwide. Nanoparticles (NPs), as a key component of nanomedicine, provide alternative options for promoting the efficacy of cancer therapy. Current conventional cancer models have limitations in predicting the effects of various cancer treatments. To overcome these limitations, biomimetic and novel 'tumor-on-a-chip' platforms have emerged with other innovative biomedical engineering methods that enable the evaluation of NP-based cancer therapy. In this review, we first describe cancer models for evaluation of NP-based cancer therapy techniques, and then present the latest advances in 'tumor-on-a-chip' platforms that can potentially facilitate clinical translation of NP-based cancer therapies.