Co-delivery of the autophagy inhibitor si-Beclin1 and the doxorubicin nano-delivery system for advanced prostate cancer treatment

Resistance to apoptosis is a key mechanism underlying how cancer cells evade tumor therapy. Autophagy can prevent anticancer drug-induced apoptosis and promote tumor resistance. The purpose of this study was to improve the sensitivity and efficacy of chemotherapeutic drugs through the inhibition of autophagy. Hydrophobic doxorubicin–hydrazone–caproyl–maleimide (DOX-EMCH) and autophagy-inhibiting si-Beclin1 were simultaneously delivered via the amphiphilic peptide micelle system (Co-PMs) using poly(L-arginine)–poly(L-histidine)–DOX-EMCH as the copolymer building unit. The constructed micelle system promoted the escape of si-Beclin1 from endosomes and the release of DOX into the nucleus. The Co-PMs exhibited 2.7-fold higher cytotoxicity and proapoptotic ability in PC3 cells than DOX treatment alone, demonstrating that si-Beclin1 could inhibit the autophagic activity of prostate cancer (PCa) cells by targeting the type III PI3K pathway and enhance the sensitivity of the cells to the chemotherapeutic drug DOX. In addition, the peptide micelles successfully passively targeted DOX and si-Beclin1 to the tumor tissue. Compared with DOX or si-Beclin1 treatment alone, the Co-PMs showed a 3.4-fold greater tumor inhibitory potential in vivo, indicative of a significant antiproliferative effect. Our results suggested that the Co-PMs developed in this study have the potential to combine autophagy inhibition and chemotherapy in cancer treatment, especially for PCa.

A Facile Route to Synthesis of Hierarchically Porous Carbon via Micelle System for Bifunctional Electrochemical Application

Well-ordered hierarchically porous carbon (HPC) nanomaterials have been successfully synthesized by a facile, efficient, and fast heated-evaporation induced self-assembly (HISA) method. A micelle system was employed as the template by using the HISA method for the first time, which possessed great potential in the large-scale production of HPC materials. Various surfactants, including triblock copolymer Pluronic F127, P123, F108, and cationic CTAB, were used in the polymerization process as templates to reveal the relationship between the structure of surfactants and architecture of the as-prepared HPCs. Transmission electron microscopy (TEM), X-ray diffraction (XRD), Nitrogen adsorption, and Fourier transform infrared (FTIR) measurements were conducted to investigate the morphology, structure, and components of HPCs, which further confirmed the well-ordered and uniform mesoporous structure. The as-prepared HPC sample with F127 possessed the largest specific surface area, suitable pore size, and well-ordered mesoporous structure, resulting in better electrochemical performance as electrodes in the fields of energy storage and conversion system. Doped with the metallic oxide MnO2, the MnO2/HPC composites presented the outstanding electrochemical activity in supercapacitor with a high specific capacitance of 531.2 F g−1 at 1 A g−1 and excellent cycling performance with little capacity fading, even after 5,000 cycles. Moreover, the obtained sample could also be applied in the fields of oxygen reduction reaction (ORR) for its abundant active sites and regulate architecture. This versatile approach makes the mass industrial production of HPC materials possible in electrochemical applications through a facile and fast route.

Function Of Surfactants In Immobilization of Cellulase And Multiphase Hydrolysis: A Review

Surfactants, especially non-ionic surfactants, play an important role in the preparation of nanocarriers and can also promote the enzymatic hydrolysis of lignocellulose. A broad overview of the current status of surfactants on the immobilization of cellulase is provided in this review. In addition, the restricting factors in cellulase immobilization in the complex multiphase hydrolysis system are discussed, including the carrier structure characteristics, solid-solid contact obstacles, external diffusion resistance, limited recycling frequency, and invalid combination of enzyme active centers. Furthermore, promising prospects of cellulase-oriented immobilization are proposed, including the hydrophilic-hydrophobic interaction of surfactants and cellulase in the oil-water reaction system, the reversed micelle system of surfactants, and the possible oriented immobilization mechanism.

Hierarchical Core–Shell Fe3O4@mSiO2@Chitosan Nanoparticles for pH-Responsive Drug Delivery

Hierarchical nanoparticles are of great interest because they possess unique physicochemical properties and multiple functionalities, providing a wealth of possibilities for various applications. In this work, we have developed a well-designed method to prepare hierarchical magnetic nanoparticles Fe3O4@mSiO2@CS by integrating a solvothermal method for synthesizing the Fe3O4 core, a dualtemplating micelle system for preparing a layer of mesoporous silica (mSiO2) shell, and a silane coupling method via γ-glycidoxypropyltrimethoxysilane for binding a chitosan (CS) layer on the silica surface. The porous hierarchical nanoparticles were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering nanoparticle size analyzer, and specific surface area and pore size analyzer. The loading capacity and the release behavior of the as-prepared nanoparticles for doxorubicin hydrochloride were studied, and it was found that the drug release rate was faster at pH 6.0 than at pH 7.4, revealing the pH-responsive property of the nanoparticles.

Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.

PEG-poly(amino acid)s/EpCAM aptamer multifunctional nanoparticles arrest the growth and metastasis of colorectal cancer

A new nano-micelle system with better water solubility and sustained drug release effect, targeting colorectal cancer stem cells, effectively inhibits the growth and metastasis of colorectal cancer via the Wnt/β-catenin signaling pathway.

Relaxometry models compared with Bayesian technique: Ganglioside micelle example

In this work a methodology to perform Bayesian model-comparison is developed and exemplified in the analysis of magnetic relaxation dispersion (NMRD) experiments of water in Ganglioside micelle system. The NMRD...