Cancer cell-derived EVs can be used as effective carriers of Paclitaxel to their parental cells, bringing the drug into the cells through an endocytic pathway and increasing its cytotoxicity. However, due to the increased cell viability, the use of cancer cell-derived EVs must be further investigated before any clinical applications can be designed.

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Polymeric vectors for gene delivery are a promising alternative for clinical applications as they are generally safer than viral counterparts. Our objective was to further our mechanistic understanding of polymer structure-function relationships to allow rational design of new biomaterials. Utilizing poly(beta-amino ester)s (PBAE), we investigated polymer-DNA binding by systematically varying polymer molecular weight, adding single carbons to the backbone and sidechain of the monomers that compose the polymers, as well as varying the type of polymer endgroup. We then sought to correlate how PBAE binding affects polyplex diameter and zeta potential, transfection efficacy and its associated cytotoxicity in human breast and brain cancer in vitro. Amongst other trends, we observed in both cell lines the PBAE-DNA binding constant is biphasic with transfection efficacy and optimal values for transfection efficacy are in the range of 1-6×104 M−1. A binding constant in this range is necessary but not sufficient for effective transfection.

Skottman, H. (2015). Biomimetic collagen I and IV double layer Langmuir-Schaefer films as microenvironment for human pluripotent stem cell derived retinal pigment epithelial cells. BIOMATERIALS, 51, 257-269. DOI: 10.1016/j.biomaterials.2015 AbstractThe environmental cues received by the cells from synthetic substrates in vitro are very different from those they receive in vivo. In this study, we applied the Langmuir-Schaeffer (LS) deposition, a variant of Langmuir-Blodgett technique, to fabricate a biomimetic microenvironment mimicking the structure and organization of native Bruch's membrane for the production of the functional human embryonic stem cell derived retinal pigment epithelial (hESC-RPE) cells. Surface pressure-area isotherms were measured simultaneously with Brewster angle microscopy to investigate the self-assembly of human collagens type I and IV on airsubphase interface. Furthermore, the structure of the prepared collagen LS films was characterized with scanning electron microscopy, atomic force microscopy, surface plasmon resonance measurements and immunofluorescent staining. The integrity of hESC-RPE on double layer LS films was investigated by measuring transepithelial resistance and permeability of small molecular weight substance. Maturation and functionality of hESC-RPE cells on double layer collagen LS films was further assessed by RPE-specific gene and protein expression, growth factor secretion, and phagocytic activity. Here, we demonstrated that the prepared collagen LS films have layered structure with oriented fibers corresponding to architecture of the uppermost layers of Bruch's membrane and result in increased barrier properties and functionality of hESC-RPE cells as compared to the commonly used dip-coated controls.

Triplet energy transfer enables efficient Z-to-E photoswitching of azobenzenes even with near-infrared light. Ultrafast intersystem crossing of azobenzene makes the process entropy-driven and enables the use of endothermic sensitizer-azobenzene pairs.

The mechanism of polyethylenimine–DNA and poly(L-lysine)–DNA complex formation at pH 5.2 and 7.4 was studied by a time-resolved spectroscopic method. The formation of a polyplex core was observed to be complete at approximately N/P = 2, at which point nearly all DNA phosphate groups were bound by polymer amine groups. The data were analyzed further both by an independent binding model and by a cooperative model for multivalent ligand binding to multisubunit substrate. At pH 5.2, the polyplex formation was cooperative at all N/P ratios, whereas for pH 7.4 at N/P < 0.6 the polyplex formation followed independent binding changing to cooperative binding at higher N/Ps.

Expanding the anti-Stokes shift for triplet−triplet annihilation upconversion (TTA-UC) systems with high quantum yields without compromising power density thresholds (I th ) remains a critical challenge in photonics. Our studies reveal that such expansion is possible by using a highly endothermic TTA-UC pair with an enthalpy difference of +80 meV even in a polymer matrix 1000 times more viscous than toluene. Carrying out efficient endothermic triplet−triplet energy transfer (TET) requires suppression of the reverse annihilator-to-sensitizer TET, which was achieved by using sensitizers with high molar extinction coefficients and long triplet state lifetimes as well as optimized annihilator concentrations. Under these conditions, the sensitizer-toannihilator forward TET becomes effectively entropy driven, yielding upconversion quantum yields comparable to those achieved with the exothermic TTA-UC pair but with larger anti-Stokes shifts and even lower I th , a previously unattained achievement.

An azide-functionalized 12-armed Buckminster fullerene has been monosubstituted in organic media with a substoichiometric amount of cyclooctyne-modified oligonucleotides. Exposing the intermediate products then to the same reaction (i.e., strain-promoted alkyne–azide cycloaddition, SPAAC) with an excess of slightly different oligonucleotide constituents in an aqueous medium yields molecularly defined monofunctionalized spherical nucleic acids (SNAs). This procedure offers a controlled synthesis scheme in which one oligonucleotide arm can be functionalized with labels or other conjugate groups (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA, and Alexa-488 demonstrated), whereas the rest of the 11 arms can be left unmodified or modified by other conjugate groups in order to decorate the SNAs’ outer sphere. Extra attention has been paid to the homogeneity and authenticity of the C 60 -azide scaffold used for the assembly of full-armed SNAs.