Synergistic effects of multidrug/material combination deliver system for anti-mutidrug-resistant tumor.

Multidrug resistance (MDR) is a public health issue of particular concern, for which nanotechnology-based multidrug delivery systems are considered among the most effective suppressive strategies for such resistance in tumors. However, for such strategies to be viable, the notable shortcomings of reduced loading efficiency and uncontrollable drug release ratio need to be addressed. To this end, we developed a novel "multidrug/material" co-delivery system, using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS, P-gp efflux pump inhibitor) and poly(amidoamine) (PAMAM) to fabricate a precursor material with the properties of reversing MDR and having a long-cycle. Further, to facilitate multidrug co-delivery, we loaded doxorubicin(Dox) and curcumin(Cur, cardiotoxicity modifier and P-gp inhibitor) into PAMAM-TPGS nano-micelles respectively, and mixed in appropriate proportions. The multidrug/material co-delivery system thus obtained was characterized by high drug loading and a controllable drug release ratio in the physiological environment. More importantly, in vitro and in vivo pharmacodynamic studies indicated that the multidrug/material co-delivery system facilitated the reversal of MDR. Moreover, the system has increased anti-tumor activity and is biologically safe. We accordingly propose that the "multidrug/material" co-delivery system developed in this study could serve as a potential platform for reversing MDR and achieving safe and effective clinical treatment.

Enzyme-responsive nano-drug delivery system for combined antitumor therapy.

Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star-shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.

Applications of biomaterials for immunosuppression in tissue repair and regeneration.

The immune system plays an essential role in tissue repair and regeneration. Regardless of innate or adaptive immune responses, immunosuppressive strategies such as macrophage polarization and regulatory T (Treg) cell induction can be used to modulate the immune system to promote tissue repair and regeneration. Biomaterials can improve the production of anti-inflammatory macrophages and Treg cells by providing physiochemical cues or delivering therapeutics such as cytokines, small molecules, microRNA, growth factors, or stem cells in the damaged tissues. Herein, we present an overview of immunosuppressive modulation by biomaterials in tissue regeneration and highlight the mechanisms of macrophage polarization and Treg cell induction. Overall, we foresee that future biomaterials for regenerative strategies will entail more interactions between biomaterials and the immune cells, and more mechanisms of immunosuppression related to T cell subsets remain to be discovered and applied to develop novel biomaterials for tissue repair and regeneration. STATEMENT OF SIGNIFICANCE: Immunosuppression plays a key role in tissue repair and regeneration, and biomaterials can interact with the immune system through their biological properties and by providing physiochemical cues. Here, we summarize the studies on biomaterials that have been used for immunosuppression to facilitate tissue regeneration. In the first part of this review, we demonstrate the crucial role of macrophage polarization and induction of T regulatory (Treg) cells in immunosuppression. In the second part, distinct approaches used by biomaterials to induce immunosuppression are introduced, which show excellent performance in terms of promoting tissue regeneration.

Membrane autopsy deciphering keystone microorganisms stubborn against online NaOCl cleaning in a full-scale MBR.

The knowledge about membrane biofouling evolution in full-scale membrane bioreactor (MBR) applications is quite lacking, notwithstanding a few lab-scale investigations. For the first time, this study elaborated the effect of online NaOCl cleaning on the dynamic development of membrane biofilm microbiota during long-term operation of a large-scale MBR for municipal wastewater treatment (40,000 m3/d). Four times of membrane autopsies were conducted during 160 days operation to scrutinize the microbial community and concomitant organic foulants. The transmembrane pressure difference (TMP) development revealed limited effect of 30 min online NaOCl cleaning on long-term biofouling removal. NaOCl not only altered the structure of biofilm communities but also increased the richness and evenness on early fouling stages. Meanwhile, network analysis revealed the keystone taxa f_Comamonadaceae that played key roles in stabilizing community structure and developing anti-cleaning and irreversible fouling propensity of the biofilm. NaOCl cleaning also impacted the evolving of keystone taxa by intensifying the competition between the dominated taxa f_Moraxellaceae and other species during early fouling stages. Furthermore, the succession of the biofilm microbiota synchronously accelerated the TMP increase and the accumulation of organic foulants including polysaccharides, aromatic proteins and soluble microbial products during biofilm maturation. These identified key stubborn foulants shed light on limitations of current online NaOCl cleaning and provide guidance to optimize the efficiency of online chemical cleaning protocols in full-scale MBR operations.

A novel operational strategy to enhance wastewater treatment with dual-anode assembled microbial desalination cell.

This study introduced a novel dual-anode assembled microbial desalination cell to enhance the performance of domestic wastewater treatment. Two parallel units were fabricated with two anodes and one cathode, which is separated by two ion exchange membrane stacks. A hollow fiber membrane module was inserted in the cathode to intercept suspended solids and microbes. Based on preliminary experiments where synthetic wastewater was utilized, anode hydraulic retention time of 10 h and cathode aeration rate of 0.16 m3/h were chosen as the operating conditions. By innovatively connecting four membrane stacks in cascades, which multiplied flow rate without adding extra circulation pumps, the desalination rate of the system was improved 214.8% compared with single membrane stack mode. When modified domestic wastewater was applied, the average removal efficiencies of chemical oxygen demand, ammonia nitrogen, total nitrogen and total phosphorous reached 96.9%, 99.0%, 98.0% and 98.3%, respectively.