Theoretical investigations of phase separation in polyelectrolyte solutions have so far assumed that the effective charge of the polyelectrolyte chains is fixed. The ability of the polyelectrolyte chains to self-regulate their effective charge due to the self-consistent coupling between ionization equilibrium and polymer conformations, depending on the dielectric constant, temperature, and polymer concentration, affects the critical phenomena and phase transitions drastically. By considering salt-free polyelectrolyte solutions, we show that the daughter phases have different polymer charges from that of the mother phase. The critical point is also altered significantly by the charge self-regularization of the polymer chains. This work extends the progress made so far in the theory of phase separation of strong polyelectrolyte solutions to a higher level of understanding by considering chains which can self-regulate their charge.

A general approach is proposed that allows for quantifying the relative toxic contribution of ions released from metallic nanoparticles and of the particles themselves, as exemplified for the case of differently shaped zinc oxide (ZnO) nanoparticles (NPs) exposed to zebrafish embryos. First of all, the toxicity of suspensions of ZnO nanoparticles (NP(total))--nanospheres, nanosticks, cuboidal submicron particles (SMPs), and Zn(NO3)2--to the embryos was assessed. The observed toxicity of ZnO NP(total) is assumed to result from the combined effect of the particles present in the suspensions (NP(particle)) and of the dissolved Zn(2+) ions released from the particles (NP(ion)). Different addition models were used to explicitly account for the toxicity of NP(particle). The median lethal concentrations (LC50) of NP(particle) of nanospheres, nanosticks, and SMPs were found to range between 7.1 mg Zn/L and 11.9 mg Zn/L (i.e., to differ by a factor of 1.7). Behavioral performance showed no significant differences among all types of the NP(particle). The median effective concentrations (EC50) of the particles were found to range between 1.0 mg Zn/L and 2.2 mg Zn/L. At the LC50 of each particle suspension, the main contribution to lethality to zebrafish embryos was from the NP(particle) (52%-72%). For hatching inhibition, the NP(particle) was responsible for 38% to 83% of the adverse effects observed. The ZnO nanosticks were more toxic than any of the other NPs with regard to the endpoints mortality and hatching inhibition. The main contribution to toxicity to zebrafish embryos was from the NP(particle) at the LC50 and EC50 of each particle suspension.

We present a theory for polyelectrolyte gels that allow the effective charge of the polymer backbone to self-regulate. Using a variational approach, we obtain an expression for the free energy of gels that accounts for the gel elasticity, free energy of mixing, counterion adsorption, local dielectric constant, electrostatic interaction among polymer segments, electrolyte ion correlations, and self-consistent charge regularization on the polymer strands. This free energy is then minimized to predict the behavior of the system as characterized by the gel volume fraction as a function of external variables such as temperature and salt concentration. We present results for the volume transition of polyelectrolyte gels in salt-free solvents, solvents with monovalent salts, and solvents with divalent salts. The results of our theoretical analysis capture the essential features of existing experimental results and also provide predictions for further experimentation. Our analysis highlights the importance of the selfregularization of the effective charge for the volume transition of gels in particular, and for charged polymer systems in general. Our analysis also enables us to identify the dominant free energy contributions for charged polymer networks and provides a framework for further investigation of specific experimental systems.

Three sizes of copper nanoparticles (Cu NPs; 25 nm, 50 nm, and 100 nm), 1 submicron-sized particle, and Cu(NO3 )2 were added to the culture buffer of zebrafish embryos from 24 h postfertilization to 120 h postfertilization. In suspensions of Cu NPs and the Cu submicron-sized particle, the main contribution to the toxicity to zebrafish embryos was from the particle form of Cu particles (Cu NPparticle , >71%) rather than from dissolved Cu from the Cu particles (Cu NPion ). All particles tested as well as copper nitrate inhibited hatching, altered behavioral responses, and increased the incidence of malformations. Different kinds of abnormalities were observed in the morphology and behavior of the zebrafish embryos, depending on the particle size of the Cu suspensions tested. The median lethal concentrations of Cu NPparticle (25 nm, 50 nm, and 100 nm), the submicron-sized particle, and copper nitrate were 0.58 mg/L, 1.65 mg/L, 1.90 mg/L, 0.35 mg/L, and 0.70 mg/L, respectively. Submicron-sized particles and copper nitrate were more toxic than Cu NPs, and smaller Cu NPs were more toxic than larger Cu NPs. Dissolution of Cu NPs and the subsequent ion toxicity was not the primary mechanism of Cu NP toxicity in zebrafish embryos.

Near-infrared photoimmunotherapy (NIR-PIT), which employs monoclonal antibody (mAb)-phototoxic phthalocyanine dye IR700 conjugates, permits the specific, image-guided and spatiotemporally controlled elimination of tumor cells. Here, we report the highly efficient NIR-PIT of human tumor xenografts initiated from patient-derived cancer stem cells (CSCs). Using glioblastoma stem cells (GBM-SCs) expressing the prototypic CSC marker AC133/CD133, we also demonstrate here for the first time that NIR-PIT is highly effective against brain tumors. The intravenously injected theranostic AC133 mAb conjugate enabled the non-invasive detection of orthotopic gliomas by NIR fluorescence imaging, and reached AC133+ GBM-SCs at the invasive tumor front. AC133-targeted NIR-PIT induced the rapid cell death of AC133+ GBM-SCs and thereby strong shrinkage of both subcutaneous and invasively growing brain tumors. A single round of NIR-PIT extended the overall survival of mice with established orthotopic gliomas by more than a factor of two, even though the harmless NIR light was applied through the intact skull. Humanised versions of this theranostic agent may facilitate intraoperative imaging and histopathological evaluation of tumor borders and enable the highly specific and efficient eradication of CSCs.