Reduction-responsive dextran-based Pt(IV) nano-prodrug showed a synergistic effect with doxorubicin for effective melanoma treatment.

Melanoma, the deadliest skin cancer with high metastasis potential, has posed a great threat to human health. Accordingly, early efficient blocking of melanoma progression is vital in antitumor treatment. Herein, a reduction-responsive dextran-based Pt(IV) nano-prodrug (PDPN) was synthesized and used for doxorubicin (DOX) delivery to combat melanoma synergistically. First, PDPN was prepared by one-pot chemical coupling of carboxylated methoxy poly(ethylene glycol) (mPEG), dextran (Dex), and the crosslinking agent cisPt (IV)-COOH. PDPN had a spherical structure (Rh = 34 ± 11.3 nm). Then, DOX was encapsulated into the PDPN core to form DOX-loaded PDPN (PDPN-DOX). The obtained PDPN-DOX displayed reduction-responsive release of DOX and Pt, thus showing a synergistic anticancer effect in B16F10 cells (combination index, 0.46). Furthermore, in vivo experiments demonstrated that PDPN-DOX was effective for the synergistic treatment of subcutaneous melanoma. Collectively, the as-prepared PDPN could serve as a promising and versatile nano-prodrug carrier for the co-delivery of chemotherapeutics in tumor combination therapy.

Low-Loss, High-Transparency Luminescent Solar Concentrators with a Bioinspired Self-Cleaning Surface.

Luminescent solar concentrators (LSCs) have emerged as a disruptive technology that can potentially enable carbon-neutral buildings. The issues with current LSCs, however, are low optical efficiencies and limited long-term outdoor stability. Here we simultaneously address them by developing an LSC with aggregation-induced-emission (AIE) molecules embedded in a polydimethylsiloxane (PDMS) matrix. The AIE-emitter displayed a near unity emission quantum yield when embedded in the PDMS and the apparent absorption-emission Stokes shift reached 0.59 eV, effectively suppressing the reabsorption loss of waveguided photons inside an LSC. Moreover, the surface texture of the PDMS matrix was engineered using a bioinspired nanolithography method with a natural lotus leaf as the template. This allowed the fabricated AIE-PDMS LSC to inherit the superhydrophobic, self-cleaning properties of the leaf and meanwhile to possess a light-trapping capability. Our 100 cm2 LSC, when coupled with commercial Si PVs, delivered efficient solar power conversion, high visible transmittance, and high working stability.

Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma.

BACKGROUND: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. PURPOSE: We proposed a facile "in situ drug conjugation-induced self-assembly" strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. METHODS: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. RESULTS: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. CONCLUSION: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.

Mathematical modeling and finite element simulation of slow release of drugs using hydrogels as carriers with various drug concentration distributions.

In drug release systems using hydrogels as carriers, the presence of the polymer network will reduce the drug release rate, which can extend the release period. For a controlled-release process of drug, usually the ideal situation is to get a zero-order drug release rate. In this paper, the mathematical model of hydrogel swelling processes is constructed on the basis of a biphasic theory, and then an integrated equation that considers both water convection and drug diffusion phenomena is used to describe the drug release process. The effects of the initial drug concentration with nonuniform distributions along the radial direction of hydrogel carriers on the release of drugs are studied through simulating two-dimensional hydrogel swelling processes by means of the COMSOL Multiphysics software. The simulation results show that along with the hydrogel swelling, the drug release rate is changing, and the major influencing factors of the drug release rate are water convection and drug diffusion coefficient, which are affected by water volume fraction, drug concentration distribution in matrix, and carrier radius. The results also indicate that the initial drug concentration distribution following a sine curve can result in an ideal zero-order release process.

Comparison of the multiphasic model and the transport model for the swelling and deformation of polyelectrolyte hydrogels.

Polyelectrolyte hydrogel is a ternary mixture of water, polymer network and mobile ions. The present paper examined two popular models describing the swelling and deformation behaviors of polyelectrolyte hydrogels, i.e. the multiphasic model and the transport model. The water flow, the network deformation and the ionic diffusion are coupled in the multiphasic model, and the gradient of the fluid pressure is taken as the driving force for the network deformation. However, the water flow is neglected in the transport model with the ionic osmotic pressure taking the role of fluid pressure. Two simplified experiments, i.e. the free swelling of a hydrogel sphere in response to the concentration change of the external salt solution and the bending deformation of a hydrogel strip under an external electric field, are simulated by the two models. Simulation shows that the two models lead to the same predictions for the swelling equilibrium of the hydrogel sphere but different predictions for the swelling kinetics of the hydrogel sphere and the deformation of the hydrogel strip under the external electric field. These are due to the fact that the two models are equivalent in thermodynamic equilibrium situations, but in thermodynamic non-equilibrium situations, the transport model is no longer applicable as it neglects the water flow in the hydrogel and takes the ionic osmotic pressure as a mechanical parameter to play the role of swelling pressure. The present work will be helpful for understanding the hydrodynamics of polyelectrolyte hydrogels and the application of the two models.