In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.

Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK]2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, which induces the aggregation of ALP and the protein-lipid phase separation on cell membrane. Consequently, KYp internalization is 2-fold enhanced compared to non-responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self-assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy.

Cell membrane-specific self-assembly of peptide nanomedicine induces tumor immunogenic death to enhance cancer therapy.

Immunogenic cell death (ICD), as an unusual cell death pattern, mediates cancer cells to release a series of damage-associated molecular patterns (DAMPs), and is widely used in the field of cancer immunotherapy. Injuring the cell membrane can serve as a novel ICD initiation strategy. In this study, a peptide nanomedicine (PNpC) is designed using the fragment CM11 of cecropin, which is effective in disrupting cell membranes because of its α-helical structure. PNpC self-assembles in situ in the presence of high levels of alkaline phosphatase (ALP) on the tumor cell membrane, transforming from nanoparticles to nanofibers, which reduces the cellular internalization of the nanomedicine and increases the interaction between CM11 and tumor cell membranes. Both in vitro and in vivo results indicate that PNpC plays a significant role in killing tumor cells by triggering ICD. The ICD induced by the destruction of the cancer cell membrane is accompanied by the release of DAMPs, which promotes the maturation of DCs and facilitates the presentation of tumor-associated antigens (TAA), resulting in the infiltration of CD8+ T cells. We believe that PNpC can trigger ICD while killing cancer cells, providing a new reference for cancer immunotherapy.

Bridging micro/nano-platform and airway allergy intervention.

Allergic airway diseases, with incidence augmenting visibly as industrial development and environmental degradation, are characterized by sneezing, itching, wheezing, chest tightness, airway obstruction, and hyperresponsiveness. Current medical modalities attempt to combat these symptoms mostly by small molecule chemotherapeutants, such as corticosteroids, antihistamines, etc., via intranasal approach which is one of the most noninvasive, rapid-absorbed, and patient-friendly routes. Nevertheless, inherent defects for irritation to respiratory mucosa, drug inactivation and degradation, and rapid drug dispersal to off-target sites are inevitable. Lately, intratracheal micro/nano therapeutic systems are emerging as innovative alternatives for airway allergy interventions. This overview introduces several potential application directions of mic/nano-platform in the treatment of airway allergic diseases, including carriers, therapeutic agents, and immunomodulators. The improvement of the existing drug therapy of respiratory allergy management by micro/nano-platform is described in detail. The challenges of the micro/nano-platform nasal approach in the treatment of airway allergy are summarized and the development of micro/nano-platform is also prospected. Although still a burgeoning area, micro/nano therapeutic systems are gradually turning to be realistic orientations as crucial future alternative therapeutic options in allergic airway inflammation interventions.

Skin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regeneration.

Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the commercial antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clinical wound management and skin regeneration.

Chitosan-centered nanosystems as sustained therapeutics for allergic rhinitis intervention: Inhibition of histamine-induced cascades.

Allergic rhinitis (AR), histamine-mediated upper airway inflammatory disorder, is characterized by sneezing, itching, airway hyperreactivity, etc. Though it is clinically well-managed by non-invasive inhaled antihistamines, for example, ketotifen (KT, histamine release inhibitor) and cetirizine (CTZ, histamine receptor antagonist), inherent defects of short mucosal in situ retention, frequent administration resulting in irritation to mucosa, and lack of target-specific sequential release of dual drug systems which have been proven to be more effective are inevitable, urging for alternative therapeutic strategies. Recent advances in nanotechnology may be pivotal to generating muco-adhesive nanosystems, which is desirable to prolong local retention, reduce dosing frequency and relieve mucosal irritation. In this regard, KT incorporated and CTZ decorated hydroxybutyl chitosan nanoparticles (K âŠ‚ CH NPs) were fabricated as nasal adaptive sequential release dual drug system for long-term AR therapy. Nasal adaptive morphology transformation and two-step payload release up to 72 h were achieved in vitro, with ~ 3-fold higher bio-adhesivity over free drugs appeared. K âŠ‚ CH NPs accomplished longer histamine release inhibition (~ 24 h) and histamine H1 receptor antagonism (~ 6 h), compared with free KT&CTZ of ~ 12 h and ~ 2 h, respectively. The nanosystems provided comparable anti-allergic effect to free antihistamines via successive intranasal dropping in AR rat, while encouragingly, significantly (P < 0.05) better therapeutic efficacy at reduced treatment frequency (every 4 days) and dose (half-dose). Therefore, the outcomes establish K âŠ‚ CH NPs as effective low-dose and long-interval administered nanosystems to ameliorate histamine-mediated AR inflammation, which could in principal find extensive utilizations in respiratory allergy intervention.

Nanosystems as curative platforms for allergic disorder management.

Allergy, IgE-mediated inflammatory disorders including allergic rhinitis, asthma, and conjunctivitis, affects billions of people worldwide. Conventional means of allergy management include allergen avoidance, pharmacotherapy, and emerging therapies. Among them, chemotherapeutant intake via oral, intravenous, and intranasal routes is always the most common mean. Although current pharmacotherapy exhibit splendid anti-allergic effects, short in situ retention, low bioavailability, and systemic side effects are inevitable. Nowadays, nanoplatforms have provided alternative therapeutic options to obviate the existing weakness via enhancing the solubility of hydrophobic therapeutic agents, achieving in situ drug accumulation, exhibiting controlled and long-time drug release at lesion areas, and providing multi-functional therapeutic strategies. Herein, we highlight the clinical therapeutic strategies and deal with characteristics of the nanoplatform design in allergy interventions via intratracheal, gastrointestinal, intravenous, and ocular paths. The promising therapeutic utilization in a variety of allergic disorders is discussed, and recent perspectives on the feasible advances of nanoplatforms in allergy management are also exploited.

Multilayer calcium alginate beads containing Diatom Biosilica and Bacillus subtilis as microecologics for sewage treatment.

Organic matter pollution and heavy metal pollution have become one of the main problems in water recycling, and the strategy to simultaneously remove soluble organic matter and metal ions is crucial for sewage treatment. In this study, multilayer calcium Alginate beads (n-Alg-DBs-Bas) containing Diatom Biosilica (DBs) and Bacillus subtilis (Bas) were designed as microecologics for sewage treatment. The introduction of DBs in beads and the multilayer structure could promote Bas growth, prolong the stability of the beads, and enhance the adsorption of beads, further improve the sewage treatment efficiency. The organic matter degradation of 3 layered Alg-DBs-Bas reached to 68.23 ± 0.95 % of COD and 58.88 ± 0.84 % of NH4+-N, and the metal ion adsorption was up to 119.31 mg/g for Fe3+, 110.81 mg/g for Zn2+ and 141.34 mg/g for Cu2+. The prepared multilayer calcium alginate beads combined organic matter degradation and metal ions absorption, which is significant for environmental applications.