Mushroom-derived bioactive components with definite structures in alleviating the pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a complicated neurodegenerative condition with two forms: familial and sporadic. The familial presentation is marked by autosomal dominance, typically occurring early in individuals under 65 years of age, while the sporadic presentation is late-onset, occurring in individuals over the age of 65. The majority of AD cases are characterized by late-onset and sporadic. Despite extensive research conducted over several decades, there is a scarcity of effective therapies and strategies. Considering the lack of a cure for AD, it is essential to explore alternative natural substances with higher efficacy and fewer side effects for AD treatment. Bioactive compounds derived from mushrooms have demonstrated significant potential in AD prevention and treatment by different mechanisms such as targeting amyloid formation, tau, cholinesterase dysfunction, oxidative stress, neuroinflammation, neuronal apoptosis, neurotrophic factors, ER stress, excitotoxicity, and mitochondrial dysfunction. These compounds have garnered considerable interest from the academic community owing to their advantages of multi-channel, multi-target, high safety and low toxicity. This review focuses on the various mechanisms involved in the development and progression of AD, presents the regulatory effects of bioactive components with definite structure from mushroom on AD in recent years, highlights the possible intervention pathways of mushroom bioactive components targeting different mechanisms, and discusses the clinical studies, limitations, and future perspectives of mushroom bioactive components in AD prevention and treatment.

Feathery Tellurium-Selenium Heterostructural Nanoadjuvant for the Synergistic Treatment of Bacterial Infections.

Antibacterial nanoagents with well-controlled structures are greatly desired to address the challenges of bacterial infections. In this study, a featherlike tellurium-selenium heterostructural nanoadjuvant (TeSe HNDs) was created. TeSe HNDs produced 1O2 and had high photothermal conversion efficiency when stimulated with 808 nm near-infrared (NIR) light. To create a synergistic treatment system (TeSe-ICG) with better photothermal and photodynamic capabilities, the photosensitizer indocyanine green (ICG) was then added. With a bactericidal rate of more than 99%, the NIR-mediated TeSe-ICG demonstrated an efficient bactericidal action against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). In addition, TeSe-ICG was also effective in treating wound infections and could effectively promote wound healing without obvious toxic side effects. In conclusion, TeSe-ICG is expected to be a good candidate for the treatment of bacterial infections.

Modulation of cancer-associated fibroblasts by nanodelivery system to enhance efficacy of tumor therapy.

Cancer-associated fibroblasts (CAFs) are the most common cells in the tumor stroma and are essential for tumor development and metastasis. While decreasing the release and infiltration of nanomedicine through nonspecific internalization, CAFs specifically increase solid tumor pressure and interstitial fluid pressure by secreting tumor growth- and migration-promoting cytokines, which increases vascular and organ pressure caused by solid tumor pressure. Nanoparticles have good permeability and can penetrate tumor tissue to reach the lesion area, inhibiting tumor growth. Thus, CAFs are used as modifiable targets. Here, the authors review the biological functions, origins and biomarkers of CAFs and summarize strategies for modulating CAFs in nanodelivery systems. This study provides a prospective guide to modulating CAFs to enhance oncology treatment.

Cancer-associated fibroblasts (CAFs) participate in the growth and metastasis of cancer and also suppress the penetration of antitumor drugs into the deep tumor tissue. Therefore, many researchers have sought to improve the therapeutic efficacy of nanomedicine through the regulation of CAFs. Some nanoparticles that can precisely target CAFs can slow their growth while also assisting the immune system in fighting cancer cells and releasing pressure within the tumor. These nanoparticles may pass through tumors and inhibit the growth of cancer cells. Therefore, the modulation of CAFs with nanomedicines to enhance tumor therapy is essential.

Mushroom Polysaccharides as Potential Candidates for Alleviating Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are a widespread and serious global public health burden, particularly among the older population. At present, effective therapies do not exist, despite the increasing understanding of the different mechanisms of NDs. In recent years, some drugs, such as galantamine, entacapone, riluzole, and edaravone, have been proposed for the treatment of different NDs; however, they mainly concentrate on symptom management and confer undesirable side effects and adverse reactions. Therefore, there is an urgent need to find novel drugs with fewer disadvantages and higher efficacy for the treatment of NDs. Mushroom polysaccharides are macromolecular complexes with multi-targeting bioactivities, low toxicity, and high safety. Some have been demonstrated to exhibit neuroprotective effects via their antioxidant, anti-amyloidogenic, anti-neuroinflammatory, anticholinesterase, anti-apoptotic, and anti-neurotoxicity activities, which have potential in the treatment of NDs. This review focuses on the different processes involved in ND development and progression, highlighting the neuroprotective activities and potential role of mushroom polysaccharides and summarizing the limitations and future perspectives of mushroom polysaccharides in the prevention and treatment of NDs.

Versatile Polymer-Initiating Biomineralization for Tumor Blockade Therapy.

Tumor blockade therapy is a promising penetration-independent antitumor modality, which effectively inhibits the exchange of nutrients, oxygen, and information between the tumor and surrounding microenvironments. However, the current blockade therapy strategies have limited antitumor efficacy due to defects of inadequate tumor obstruction, possible side effects, and short duration. For these reasons, a facilely synthesized versatile polymer 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-alendronate (DSPE-PEG-ALN, DPA) is developed to initiate the formation of biomineral shell around osteosarcoma as a potent physical barrier. The DSPE moiety shares a similar chemical structure with the cytomembrane, allowing the membrane insertion of DPA. The bisphosphonic acid groups in ALN attract ions to realize biomineralization around cells. After injection in the invasive osteosarcoma tissue, DPA inserts into the cytomembrane, induces continuous mineral deposition, and ultimately builds a physical barrier around the tumor. Meanwhile, ALN in DPA alleviates bone destruction by suppressing the activity of osteoclasts. Through hindering the exchange of necessary substances, the biomineralization coating inhibits the growth of primary osteosarcoma and pulmonary metastasis simultaneously. Therefore, the multifunctional polymer-initiating blockade therapy provides a promising modality for tumor inhibition in clinics with high efficacy and negligible side effects.

Polymer nanotherapeutics to correct autoimmunity.

The immune system maintains homeostasis and protects the body from pathogens, mutated cells, and other harmful substances. When immune homeostasis is disrupted, excessive autoimmunity will lead to diseases. To inhibit the unexpected immune responses and reduce the impact of treatment on immunoprotective functions, polymer nanotherapeutics, such as nanomedicines, nanovaccines, and nanodecoys, were developed as part of an advanced strategy for precise immunomodulation. Nanomedicines transport cytotoxic drugs to target sites to reduce the occurrence of side effects and increase the stability and bioactivity of various immunomodulating agents, especially nucleic acids and cytokines. In addition, polymer nanomaterials carrying autoantigens used as nanovaccines can induce antigen-specific immune tolerance without interfering with protective immune responses. The precise immunomodulatory function of nanovaccines has broad prospects for the treatment of immune related-diseases. Besides, nanodecoys, which are designed to protect the body from various pathogenic substances by intravenous administration, are simple and relatively noninvasive treatments. Herein, we have discussed and predicted the application of polymer nanotherapeutics in the correction of autoimmunity, including treating autoimmune diseases, controlling hypersensitivity, and avoiding transplant rejection.

Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy.

Cancer immunotherapy, which suppresses cancer progression by activating the anti-cancer immunity of patients, shows utility in treating multiple types of cancers. Immunogenic cell death (ICD) induced by most clinical treatment modalities plays a critical role in promoting cancer immunotherapy by releasing tumor-associated antigens and neoantigens and exposing "danger signals" to stimulate immune cells. This comment article presents the different roles of nanoparticles in various treatment modalities of cancers, including chemotherapy, radiotherapy, photodynamic and photothermal therapies, and therapy with radiated tumor cell-released nanoparticles, which often activate anti-cancer immunological effects by inducing ICD of cancer cells, and highlights the challenges and opportunities of ICD-related cancer immunotherapy in the clinic.

Poly(l-glutamic acid)-cisplatin nanoformulations with detachable PEGylation for prolonged circulation half-life and enhanced cell internalization.

PEGylation has been widely applied to prolong the circulation times of nanomedicines via the steric shielding effect, which consequently improves the intratumoral accumulation. However, cell uptake of PEGylated nanoformulations is always blocked by the steric repulsion of PEG, which limits their therapeutic effect. To this end, we designed and prepared two kinds of poly(l-glutamic acid)-cisplatin (PLG-CDDP) nanoformulations with detachable PEG, which is responsive to specific tumor tissue microenvironments for prolonged circulation time and enhanced cell internalization. The extracellular pH (pHe)-responsive cleavage 2-propionic-3-methylmaleic anhydride (CDM)-derived amide bond and matrix metalloproteinases-2/9 (MMP-2/9)-sensitive degradable peptide PLGLAG were utilized to link PLG and PEG, yielding pHe-responsive PEG-pH e-PLG and MMP-sensitive PEG-MMP-PLG. The corresponding smart nanoformulations PEG-pH e-PLG-Pt and PEG-MMP-PLG-Pt were then prepared by the complexation of polypeptides and cisplatin (CDDP). The circulation half-lives of PEG-pH e-PLG-Pt and PEG-MMP-PLG-Pt were about 4.6 and 4.2 times higher than that of the control PLG-Pt, respectively. Upon reaching tumor tissue, PEG on the surface of nanomedicines was detached as triggered by pHe or MMP, which increased intratumoral CDDP retention, enhanced cell uptake, and improved antitumor efficacy toward a fatal high-grade serous ovarian cancer (HGSOC) mouse model, indicating the promising prospects for clinical application of detachable PEGylated nanoformulations.

Polypeptide nanoformulation-induced immunogenic cell death and remission of immunosuppression for enhanced chemoimmunotherapy.

Many conventional chemotherapeutics play an immune-modulating effect by inducing immunogenic cell death (ICD) in tumor cells. However, they hardly arouse strong antitumor immune response because the immunosuppressive lymphocytes are present in the tumor microenvironment. These immunosuppressive lymphocytes include regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). We used a low dose of doxorubicin (DOX) to induce ICD in combination with immune regulator 1-methyl-DL-tryptophan (1MT) to suppress indoleamine 2,3-dioxygenase and overcome Treg- and MDSC-associated immune suppression. By co-encapsulation of DOX and 1MT into a reduction-responsive polypeptide nanogel, the drugs were simultaneously released in the tumor cells and synergistically performed antitumor efficacy. After treatment, recruitment of Tregs and MDSCs was inhibited, and the frequency of tumor-infiltrating CD8+ T cells was remarkably enhanced. These results demonstrated that the chemoimmunotherapy strategy effectively suppressed tumor growth without causing evident adverse effects, indicating its great potential in clinical cancer therapy.

Improved physicochemical stability of emulsions enriched in lutein by a combination of chlorogenic acid-whey protein isolate-dextran and vitamin E.

Lutein, as a bioactive substance, has the ability to decrease the risk of some chronic diseases, but the poor water solubility, chemical instability, and low bioaccessibility limit its wide application in foods. In this study, an emulsion-based delivery system stabilized by chlorogenic acid (CA)-whey protein isolate (WPI)-dextran (DEX) ternary conjugates was prepared and vitamin E (VE) was added to increase the chemical stability of lutein. Molecular weight and conformational information of ternary conjugates were obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. o-Phthalaldehyde results suggested that the extent of glycation was 16.4% and 19.5% for (CA-WPI)-DEX and WPI-DEX conjugates, respectively. The physicochemical stability of lutein-enriched emulsions was evaluated under different environmental stresses and long-term storage. The obtained results showed that compared with emulsions stabilized by WPI alone or binary conjugates, ternary conjugates imparted emulsions high stability under different environmental stress conditions (ionic strength, freeze-thaw, and heat) and long-term storage (within 3 weeks). VE can effectively decrease the degradation rate of lutein without changing the physical stability of emulsions. Additionally, the lutein-enriched emulsions prepared by ternary conjugates and VE exhibited a relatively high bioaccessibility. PRACTICAL APPLICATION: The ternary conjugates constructed in this paper has excellent physicochemical characteristics to stabilize emulsion, and can increase the water solubility of functional factors and reduce their degradation rate. Additionally, this conjugate was prepared by food-grade materials. Therefore, it can be used as emulsion-based delivery systems in food industrials.

Biointerface engineering nanoplatforms for cancer-targeted drug delivery.

Over the past decade, nanoparticle-based therapeutic modalities have become promising strategies in cancer therapy. Selective delivery of anticancer drugs to the lesion sites is critical for elimination of the tumor and an improved prognosis. Innovative design and advanced biointerface engineering have promoted the development of various nanocarriers for optimized drug delivery. Keeping in mind the biological framework of the tumor microenvironment, biomembrane-camouflaged nanoplatforms have been a research focus, reflecting their superiority in cancer targeting. In this review, we summarize the development of various biomimetic cell membrane-camouflaged nanoplatforms for cancer-targeted drug delivery, which are classified according to the membranes from different cells. The challenges and opportunities of the advanced biointerface engineering drug delivery nanosystems in cancer therapy are discussed.

Tackling autoimmunity with nanomedicines.

Tolerogenic immunotherapy aims to blunt pathogenic inflammation without affecting systemic immunity. However, the anti-inflammatory drugs and immunosuppressive biologics that are used in the clinic usually result in nonspecific immune cell suppression and off-target toxicity. For this reason, strategies have been developed to induce antigen-specific immune tolerance through the delivery of disease-relevant antigens by nanocarriers as a benefit of their preferential internalization by antigen-presenting cells. Herein, we discuss the recent advances in the nanotechnology-based antigen-specific tolerance approaches. Some of these designs are based on nanoparticles delivering antigens and immunoregulatory agents to modulate antigen-presenting pathways, while others directly target T cells via nanoparticle-based artificial antigen-presenting cells. These antigen-specific therapies are hoped to replace systemic immune suppression and provide long-term disease remission.

The effect of acupuncture on tumor growth and gut microbiota in mice inoculated with osteosarcoma cells.

BACKGROUND: Cancer is a complex systemic disease. As a key component of traditional Chinese medicine, acupuncture is a clinically proven medical treatment for many diseases, and it also has preventative effects as it balances the body, allowing it to self-regulate. For cancer patients, acupuncture is widely used as complementary therapy to boost the immune system and reduce the side effects of radiotherapy and chemotherapy. However, few studies have determined how acupuncture against cancer, especially in regulating the intestinal flora of the tumor-burdened mice. METHODS: We treated osteosarcoma tumor-burdened mice by using needling on different acupoints and acupoints combination, thereafter determined the effects of acupuncture on tumor growth by using imaging technology in vitro. In addition, intestinal bacteria were analyzed for further understanding the holistic and systemic treatment effects of acupuncture in osteosarcoma tumor-burdened mice. RESULTS: Acupuncture treatment can delay tumor growth and changes of intestinal bacteria in osteosarcoma tumor-burdened mice. In detail, the loss of body weight and the development of tumor volume of mice have been postposed by needling specific acupoints. In addition, acupuncture treatment has delayed the changes of the relative abundance of Bacteroidetes, Firmicutes and Candidatus Saccharibacteria at the phylum level. Moreover, the relative abundance of many bacteria (e.g., Catabacter, Acetatifactor and Aestuariispira) has been regulated by using acupuncture treatment, and the trend of structural changes of these bacteria at the genus level has also been postposed compared to that of the tumor-burdened mice model group. CONCLUSION: Our results suggest that acupuncture may provide a systemic treatment for cancer. Our findings encourage new and extensive research into the effects of acupuncture on changes of the intestinal microbiome associated with the development of cancer.

Polymer-Mediated Penetration-Independent Cancer Therapy.

The development of polymer-based drug delivery systems provides efficient modalities for cancer therapy. Most of the polymer pharmaceuticals target cancer cells directly, but the insufficient penetration always results in unsatisfactory anticancer efficacy. To break the above bottleneck, strategies of penetration-independent cancer therapy have been developed as advanced treatments for various cancers in the past decade. In this Perspective, we discussed the pros and cons of polymer-mediated biological and physical penetration-independent approaches for cancer therapy and highlighted their further prospects from bench to bedsides.

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provides the most recent advances of nanotechnology for immunostimulation and immunosuppression. In cancer immunotherapy, nanosystems play an essential role in immune cell activation and tumor microenvironment modulation, as well as combination with other antitumor approaches. In infectious diseases, many encouraging outcomes from using nanomaterial vaccines against viral and bacterial infections have been reported. In addition, nanoparticles also potentiate the effects of immunosuppressive immune cells for the treatment of inflammatory and autoimmune diseases. Finally, the challenges and prospects of applying nanotechnology to modulate immunotherapy are discussed.

Special Issue: "Smart and Functional Polymers".

Polymerization provides an efficient strategy for synthesizing macromolecules with versatile functionality [...].

PEGylated Polyurea Bearing Hindered Urea Bond for Drug Delivery.

In recent years, polyureas with dynamic hindered urea bonds (HUBs), a class of promising biomedical polymers, have attracted wide attention as a result of their controlled hydrolytic properties. The effect of the chemical structures on the properties of polyureas and their assemblies has rarely been reported. In this study, four kinds of polyureas with different chemical groups have been synthesized, and the polyureas from cyclohexyl diisocyanate and tert-butyl diamine showed the fastest hydrolytic rate. The amphiphilic polyurea composed of hydrophobic cyclohexyl-tert-butyl polyurea and hydrophilic poly(ethylene glycol) (PEG) was synthesized for the controlled delivery of the antitumor drug paclitaxel (PTX). The PTX-loaded PEGylated polyurea micelle more effectively entered into the murine breast cancer 4T1 cells and inhibited the corresponding tumor growth in vitro and in vivo. Therefore, the PEGylated polyurea with adjustable degradation might be a promising polymer matrix for drug delivery.

Evaluation of Polymer Nanoformulations in Hepatoma Therapy by Established Rodent Models.

Hepatoma is one of the most severe malignancies usually with poor prognosis, and many patients are insensitive to the existing therapeutic agents, including the drugs for chemotherapy and molecular targeted therapy. Currently, researchers are committed to developing the advanced formulations with controlled drug delivery to improve the efficacy of hepatoma therapy. Numerous inoculated, induced, and genetically engineered hepatoma rodent models are now available for formulation screening. However, animal models of hepatoma cannot accurately represent human hepatoma in terms of histological characteristics, metastatic pathways, and post-treatment responses. Therefore, advanced animal hepatoma models with comparable pathogenesis and pathological features are in urgent need in the further studies. Moreover, the development of nanomedicines has renewed hope for chemotherapy and molecular targeted therapy of advanced hepatoma. As one kind of advanced formulations, the polymer-based nanoformulated drugs have many advantages over the traditional ones, such as improved tumor selectivity and treatment efficacy, and reduced systemic side effects. In this article, the construction of rodent hepatoma model and much information about the current development of polymer nanomedicines were reviewed in order to provide a basis for the development of advanced formulations with clinical therapeutic potential for hepatoma.

Electrospun polymer micro/nanofibers as pharmaceutical repositories for healthcare.

Electrospun polymer micro/nanofibers have been widely explored as platforms for controlled delivery of therapeutic agents. Electrospun fibers are featured by large surface area, high porosity, and tunable morphology, which can be manipulated to fabricate micro/nanofibers with appropriate physicochemical properties, degradation kinetics, and drug release profiles. Many therapeutic agents can be separately or simultaneously loaded by electrospun fibers in the application of cancer therapy, adhesion prevention, wound repair, and regeneration of bone and nerve. In this review, we mainly introduce the basic principles of electrospinning, and the mechanisms and applications of electrospun micro/nanofibers for delivery of small molecule drugs, proteins, and nucleic acids in the healthcare field.

Porous Polylactide Film Plus Atorvastatin-Loaded Thermogel as an Efficient Device for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common postoperative complication that causes many kinds of organ dysfunctions. It can be minimized by the integration of physical isolation and pharmaceutical treatment. However, the gas permeability of traditional medical devices for adhesion prevention is not satisfactory, which increases the risk of infection and inflammation, thus facilitating the formation of peritoneal adhesion. In this study, a device of porous polylactide (PLA) film plus atorvastatin (ATV)-loaded thermogel was developed for peritoneal adhesion prevention. PLA film acted as a physical barrier to prevent the connection of fibrin bridges between the injured tissues and nearby normal organs. Simultaneously, ATV was released to achieve the antifibrin deposition and anti-inflammatory effect. The porous properties of PLA film and thermogel increased the gas permeability and further inhibited the inflammatory responses. The in vivo study demonstrated that the porous PLA film with ATV-loaded thermogel possessed excellent anti-inflammation ability and satisfactory antiadhesion capacity, indicating its great potential for clinical application.