Trends in Conjugated Chalcogenophenes: A Theoretical Study.

Heavy atom substitution in chalcogenophenes is a versatile strategy for tailoring and ultimately improving conjugated polymer properties. While thiophene monomers are commonly implemented in polymer designs, relatively little is known regarding the molecular properties of the heavier chalcogenophenes. Herein, we use density functional theory (DFT) calculations to examine how group 16 heteroatoms, including the radioactive polonium, affect polychalcogenophene properties including bond length, chain twisting, aromaticity, and optical properties. Heavier chalcogenophenes are more quinoidal in character and consequently have reduced band gaps and larger degrees of planarity. We consider both the neutral and radical cationic species. Upon p-type doping, bond length rearrangement is indicative of a more delocalized electronic structure, which combined with optical calculations is consistent with the polaron-model of charge storage on conjugated polymer chains. A better understanding of the properties of these materials at their molecular levels will inevitably be useful in material design as the polymer community continues to explore more main group containing polymers to tackle issues in electronic devices.

Biomimetic hydrogel supports initiation and growth of patient-derived breast tumor organoids.

Patient-derived tumor organoids (PDOs) are a highly promising preclinical model that recapitulates the histology, gene expression, and drug response of the donor patient tumor. Currently, PDO culture relies on basement-membrane extract (BME), which suffers from batch-to-batch variability, the presence of xenogeneic compounds and residual growth factors, and poor control of mechanical properties. Additionally, for the development of new organoid lines from patient-derived xenografts, contamination of murine host cells poses a problem. We propose a nanofibrillar hydrogel (EKGel) for the initiation and growth of breast cancer PDOs. PDOs grown in EKGel have histopathologic features, gene expression, and drug response that are similar to those of their parental tumors and PDOs in BME. In addition, EKGel offers reduced batch-to-batch variability, a range of mechanical properties, and suppressed contamination from murine cells. These results show that EKGel is an improved alternative to BME matrices for the initiation, growth, and maintenance of breast cancer PDOs.

Microfluidic Arrays of Breast Tumor Spheroids for Drug Screening and Personalized Cancer Therapies.

One of the obstacles limiting progress in the development of effective cancer therapies is the shortage of preclinical models that capture the dynamic nature of tumor microenvironments. Interstitial flow strongly impacts tumor response to chemotherapy; however, conventional in vitro cancer models largely disregard this key feature. Here, a proof of principle microfluidic platform for the generation of large arrays of breast tumor spheroids that are grown under close-to-physiological flow in a biomimetic hydrogel is reported. This cancer spheroids-on-a-chip model is used for time- and labor-efficient studies of the effects of drug dose and supply rate on the chemosensitivity of breast tumor spheroids. The capability to grow large arrays of tumor spheroids from patient-derived cells of different breast cancer subtypes is shown, and the correlation between in vivo drug efficacy and on-chip spheroid drug response is demonstrated. The proposed platform can serve as an in vitro preclinical model for the development of personalized cancer therapies and effective screening of new anticancer drugs.