Understanding cellular interactions and entry pathways of synthetic biomaterials are highly important to improve overall labeling and delivery efficiency. Conjugated polymer nanoparticles (CPNs) are emerging, fluorescent materials that have been used for cancer cell labeling and small interfering RNA (siRNA) delivery. In this contribution, detailed biophysical properties of CPNs including entry mechanisms and subcellular localization were studied using fluorescent-based techniques. While CPNs cause no toxicity, decreased CPN uptake was observed from cancer cells pretreated with genistein, which is an inhibitor of caveolae-mediated endocytosis (CvME). CvME was further confirmed by high co-localization with caveolin-1 proteins, which are found in the caveolae and caveosomes. Excellent photophysical properties, non-toxicity, and non-destructive delivery pathways support that CPNs are promising multifunctional carriers minimizing degradation of contents during delivery.

Multifunctional nanoparticles integrated with imaging modalities (such as magnetic resonance and optical) and therapeutic drugs are promising candidates for future cancer diagnostics and therapy. While targeted drug delivery and imaging of tumor cells have been the major focus in engineering nanoparticle probes, no extensive efforts have been made towards developing sensing probes that can confirm and monitor intra-cellular drug release events. Here, we present quantum dot (Qdot)-iron oxide (IO) based multimodal/multifunctional nanocomposite probe that is optically and magnetically imageable, targetable and capable of reporting on intra-cellular drug release events. Specifically, the probe consists of a superparamagnetic iron oxide nanoparticle core (IONP) decorated with satellite CdS:Mn/ZnS Qdots where the Qdots themselves are further functionalized with STAT3 inhibitor (an anti-cancer agent), vitamin folate (as targeting motif) and m-polyethylene glycol (m-PEG, a hydrophilic dispersing agent). The Qdot luminescence is quenched in this nanocomposite probe (“OFF” state) due to combined electron/energy transfer mediated quenching processes involving IONP, folate and STAT3 agents. Upon intracellular uptake, the probe is exposed to the cytosolic glutathione (GSH) containing environment resulting in restoration of the Qdot luminescence (“ON” state), which reports on uptake and drug release. Probe functionality was validated using fluorescence and MR measurements as well as in vitro studies using cancer cells that overexpress folate receptors.

Functionalized conducting polymer nanoparticles allow for targeted delivery, tracking by fluorescence bioimaging, and therapeutics through formation of reactive oxygen species.

Effectively controlling vector mosquito populations while avoiding the development of resistance remains a prevalent and increasing obstacle to integrated vector management. Although, metallic nanoparticles have previously shown promise in controlling larval populations via mechanisms which are less likely to spur resistance, the impacts of such particles on life history traits and fecundity of mosquitoes are understudied. Herein, we investigate the chemically well-defined cerium oxide nanoparticles (CNPs) and silver-doped nanoceria (AgCNPs) for larvicidal potential and effects on life history traits and fecundity of Aedes (Ae.) aegypti mosquitoes. When 3 rd instar larvae were exposed to nanoceria in absence of larval food, the mortality count disclosed significant activity of AgCNPs over CNPs (57.8 ±3.68% and 17.2±2.81% lethality, respectively) and a comparable activity to Ag + controls (62.8±3.60% lethality). The surviving larvae showed altered life history traits (e.g., reduced egg hatch proportion and varied sex ratios), indicating activities of these nanoceria beyond just that of a larvicide. In a separate set of experiments, impacts on oocyte growth and egg generation resulting from nanoceria-laced blood meals were studied using confocal fluorescence microscopy revealing oocytes growth-arrest at 16-24h after feeding with AgCNPblood meals in some mosquitoes, thereby significantly reducing average egg clutch. AgCNPs caused~60% mortality in 3 rd instar larvae when larval food was absent, while CNPs yielded only~20% mortality which contrasts with a previous report on green-synthesized nanoceria and highlights the level of detail required to accurately report and interpret such studies. Additionally, AgCNPs are estimated to contain much less silver (0.22 parts per billion, ppb) than the amount of Ag + needed to achieve comparable larvicidal activity (2.7 parts per million, ppm), potentially making these nanoceria ecofriendly. Finally, this work is the first study to demonstrate the until-now-unappreciated impacts of nanoceria on life history traits and interference with mosquito egg development.

Conducting polymer nanoparticles (CPNPs), composed of the conducting polymer poly[2-methoxy-5-(2-ethylhexyl-oxy)-p-phenylenevinylene] (MEH-PPV) were studied for applications in biophotonics and therapeutics. The extent of cellular uptake, cytotoxicity, and effectiveness of these nanoparticles in photodynamic therapy (PDT) was investigated for four cell lines, namely TE-71, MDA-MB-231, A549 and OVCAR3. Confocal fluorescence imaging and flow cytometry show that CPNPs are taken up only in limited quantities by TE-71, while they are taken up extensively by the cancer cell lines. The uptake among the cancer cell lines was observed to vary with cell line, with CPNPs uptake increasing from MDA-MB-231 to A549 to OVCAR3. Fluorescence imaging experiments show that the CPNPs have high brightness and appear stable in the intracellular environment. No cytotoxicity of non-photoactivated CPNPs (in dark) was observed from MTT assay. After completion of PDT, the quantitative data on cell viability suggest that cell death scales across the cell lines with CPNP uptake, is light dose dependent, and is complete for OVCAR3. In addition, for OVCAR3 apoptotic cell death is observed after PDT. The reported work illustrates the potential of the intrinsically fluorescent and photoactivateable CPNPs for application in biophotonics and therapeutics.

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In this experimental study we film the landings of Aedes aegypti mosquitoes to characterize landing behaviors and kinetics, limitations, and the passive physiological mechanics they employ to land on a vertical surface. A typical landing involves 1–2 bounces, reducing inbound momentum by more than half before the mosquito firmly attaches to a surface. Mosquitoes initially approach landing surfaces at 0.1–0.6 m/s, decelerating to zero velocity in approximately 5 ms at accelerations as high as 5.5 gravities. Unlike Dipteran relatives, mosquitoes do not visibly prepare for landing with leg adjustments or body pitching. Instead mosquitoes rely on damping by deforming two forelimbs and buckling of the proboscis, which also serves to distribute the impact force, lessening the potential of detection by a mammalian host. The rebound response of a landing mosquito is well-characterized by a passive mass-spring-damper model which permits the calculation of force across impact velocity. The landing force of the average mosquito in our study is approximately 40 $$\upmu$$ μ N corresponding to an impact velocity of 0.24 m/s. The substrate contact velocity which produces a force perceptible to humans, 0.42 m/s, is above 85% of experimentally observed landing speeds.