A Bionic Yeast Tumor Vaccine Using the Co-Loading Strategy to Prevent Post-Operative Tumor Recurrence.

Immunotherapy is an effective adjunct to surgery for preventing tumor recurrence and metastasis in postoperative tumor patients. Although mimicking microbial invasion and immune activation pathways can effectively stimulate the immune system, the limited capacity of microbial components to bind antigens and adjuvants restricts the development of this system. Here, we construct bionic yeast carriers (BYCs) by in situ polymerization of mesoporous silica nanoparticles (MSNs) within the yeast capsules (YCs). BYCs can mimic the yeast infection pathway while utilizing the loading capacity of MSNs for multiple substances. Pore size and hydrophobicity-modified BYC can be loaded with both antigen and adjuvant R848. Oral or subcutaneous injection uptake of coloaded BYCs demonstrated positive therapeutic effects as a tumor therapeutic vaccine in both the transplantation tumor model and the metastasis tumor model. 57% of initial 400 mm3 tumor recurrence models are completely cured with coloaded BYCs via combination therapy with surgery, utilizing surgically resected tumors as antigens. The BYCs construction and coloading strategy will provide insights and optimistic approaches for the development of effective and controllable cancer vaccine carriers.

Honokiol@PF127 crosslinked hyaluronate-based hydrogel for promoting wound healing by regulating macrophage polarization.

Bacterial infection, oxidative stress and inflammation are the main obstacles in wound healing. Hydrogels with moist and inherent properties are beneficial to wound healing. Here, we fabricated a honokiol-laden micelle-crosslinked hyaluronate-based hydrogel by simply mixing honokiol-laden PF127-CHO micelles, 3,3'-dithiobis(propionohydrazide) grafted hyaluronic acid and silver ions. PF127 could not only effectively load hydrophobic small molecules but also be macromolecular crosslinker for preparing hydrogels. Hyaluronic acid plays an essential role in wound healing processes including regulating macrophage polarization towards M2 phenotype. The chemical dynamic acylhydrazone crosslinking and physical crosslinking among PF127-CHO micelles constructed hydrogel's networks, which endowed hydrogel with excellent self-healing properties. PF-HA-3 hydrogel also exhibited outstanding antioxidant and antibacterial capabilities. In a full-thickness skin defect model, this degradable and biocompatible hydrogel could promote wound healing by remodeling wound tissues, regulating M2 polarization and angiogenesis. In summary, this inherent multifunctional hydrogel will provide a promising strategy for designing bioactive compounds-based wound dressings.

The combination of in situ photodynamic promotion and ion-interference to improve the efficacy of cancer therapy.

Photodynamic therapy (PDT) is proved to be a promising modality for clinical cancer treatment. However, it also suffers from a key obstacle in association with its oxygen-dependent nature which greatly limits its effective application against hypoxic tumors. Herein, on the basis of the unique property of calcium peroxide (CaO2), we propose an O2-self-supply strategy for the promotion of PDT by combining the in situ O2-generation characteristic of calcium peroxide with the photosensitive nature of porphyrin. A shell of ZIF-8 was synthesized surround the CaO2 core to prevent the CaO2 from premature decomposition and increased the loading of THPP efficiently. Depending on the in situ self-supply of O2, the photosensitizer was able to exhibit an enhanced PDT effect that significantly inhibit the growth of tumor. Moreover, the enrichment of free calcium ions derived from the decomposition of CaO2 under acidic tumor microenvironment also shows the unique ion-interference effect and contributes to the obvious inhibition against tumor growth. This work presents a synergistic strategy for the construction of a photodynamic promotion/ion-interference combined nano-platform which can also serve as an inspiration for the future design of effective nanocomposites in tumor treatment.

Facile preparation of polyphenol-crosslinked chitosan-based hydrogels for cutaneous wound repair.

The design and facile preparation of the smart hydrogel wound dressings with inherent excellent antioxidant and antibacterial capacity to effectively promote wound healing processes is highly desirable in clinical applications. Herein, a series of multifunctional hydrogels were prepared by the dynamic Schiff base and boronate ester crosslinking among phenylboronic acid (PBA) grafted carboxymethyl chitosan (CMCS), polyphenols and Cu2+-crosslinked polyphenol nanoparticles (CuNPs). The dynamic crosslinking bonds endowed hydrogels with excellent self-healing and degradable properties. Three polyphenols including tannic acid (TA), oligomeric proanthocyanidins (OPC) and (-)-epigallocatechin-3-O-gallate (EGCG) contributed to the outstanding antibacterial and antioxidant abilities of these hydrogels. The tissue adhesive capacity of hydrogels gave them good hemostatic effect. Through a full-thickness skin defect model of mice, these biocompatible hydrogels could accelerate wound healing processes by promoting granulation tissue formation, collagen deposition, M2 macrophage polarization and cytokine secretion, demonstrating that these natural-derived hydrogels with inherent physiological properties and low-cost preparation approaches could be promising dressing materials.

Research Progress on Nanoplatforms and Nanotherapeutic Strategies in Treating Glioma.

Glioma is the most common and aggressive primary intracranial tumor within the central nervous system. The blood-brain barrier (BBB) has been a great hurdle for an effective glioma treatment. To effectively treat glioma, various strategies have been applied to deliver drugs to the brain by crossing the BBB. Nanocarrier-mediated drug delivery is emerging as an effective and noninvasive system to treat glioma, showing great potential in glioma therapy. In this review, we will provide a comprehensive overview on nanocarrier-mediated drug delivery and related glioma therapy. Following an initial overview of the BBB and blood-brain-tumor barrier (BBTB) structure and characteristics, nanocarrier-mediated drug delivery strategies (liposomes, micelles, inorganic systems, polymeric nanoparticles, nanogel system, biomimetic nanoparticles, and exosomes) for crossing the BBB are discussed. Finally, nanotherapeutic techniques (imaging-mediated chemotherapy, photothermal therapy, photodynamic therapy, gene therapy, immunotherapy, ferroptosis therapy, sonodynamic therapy, chemodynamic therapy, and combination therapy) in treating glioma are summarized. In addition, this review provides some perspectives on the clinical applications of nanomedicines.

EGCG-crosslinked carboxymethyl chitosan-based hydrogels with inherent desired functions for full-thickness skin wound healing.

Hydrogel wound dressings have attracted intense and increasing interest for their extracellular matrix like properties and bioactive material delivery ability. Various functional hydrogels loaded with metals (and their oxides), antibiotics and anti-inflammatory agents have been prepared to realize antioxidant, bactericidal and anti-inflammatory effects, accelerating wound healing. Nevertheless, it is still a big challenge to facilely fabricate hydrogel wound dressings with inherent desirable properties to promote wound healing and avoid some drawbacks such as toxicity of metals and drug resistance. Herein, we facilely prepared a series of (-)-epigallocatechin-3-O-gallate (EGCG)-crosslinked carboxymethyl chitosan-based hydrogels (EP gels) with inherent antioxidant, bactericidal and adhesive properties. Gluconate-terminated polyethylene glycol (PEG-glu) was introduced into gel networks to enhance the mechanical properties. The hydrogels are constructed via borate ester crosslinking between phenylboronic acid (PBA) groups of PBA-grafted carboxymethyl chitosan (CMCS-PBA) and diol groups of EGCG and PEG-glu. The hydrogels exhibited excellent self-healing properties, desirable mechanical and adhesive strength, free radical scavenging capability and outstanding bactericidal ability against S. aureus and E. coli. In the subsequent full-thickness skin defect model of mice, EP1 gel could promote the proliferation and remodeling process such as the regeneration of epidermis, dermis, and skin appendages, deposition of collagen, and upregulation of the VEGF level, thereby accelerating the healing of damaged skin. Overall, we facilely prepared polysaccharide-based hydrogels with inherent desirable properties as promising dressings for wound repair.

Research progress on self-assembled nanodrug delivery systems.

In recent years, nanodrug delivery systems have attracted increasing attention due to their advantages, such as high drug loading, low toxicity and side effects, improved bioavailability, long circulation time, good targeting and controlled drug release efficiency. Self-assembly technology has developed rapidly in recent decades and plays an important role in the research and development of nanoscience. The combination of nanometer drug delivery and self-assembly technology can realize the self-delivery process of drugs. The facile synthesis process and strong biological affinity can both effectively enhance the therapeutic efficacy and reduce the toxicity of drugs. This combination of technologies has received wide attention in the field of nanobiomedicine. In this review, we summarize the research progress and applications of different types of self-assembled nanodrug delivery systems (amphiphilic block copolymer-based self-assembled drug delivery system, carrier-free nanodrugs, peptide-based self-assembled delivery system, metal-polyphenol self-assembly and natural small-molecule self-assembled nanodrug delivery systems), which are expected to have potential therapeutic value in the field of biomedicine in the future.

Research on endoplasmic reticulum-targeting fluorescent probes and endoplasmic reticulum stress-mediated nanoanticancer strategies: A review.

Subcellular localization of organelles can achieve accurate drug delivery and maximize drug efficacy. As the largest organelle in eukaryotic cells, the endoplasmic reticulum (ER) plays an important role in protein synthesis, folding, and posttranslational modification; lipid biosynthesis; and calcium homeostasis. Observing the changes in various metal ions, active substances, and the microenvironment in the ER is crucial for diagnosing and treating many diseases, including cancer. Excessive endoplasmic reticulum stress (ERS) can have a killing effect on malignant cells and can mediate cell apoptosis, proper modulation of ERS can provide new perspectives for the treatment of many diseases, including cancer. Therefore, the ER is used as a new anticancer target in cancer treatment. This review discusses ER-targeting fluorescent probes and ERS-mediated nanoanticancer strategies.

Research progress on nanotechnology for delivery of active ingredients from traditional Chinese medicines.

There is growing acceptance of traditional Chinese medicines (TCMs) as potential sources of clinical agents based on the demonstrated efficacies of numerous bioactive compounds first identified in TCM extracts, such as paclitaxel, camptothecin, and artemisinin. However, there are several challenges to achieving the full clinical potential of many TCMs, particularly the generally high hydrophobicity and low bioavailability. Recently, however, numerous studies have attempted to circumvent the limited in vivo activity and systemic toxicity of TCM ingredients by incorporation into nanoparticle-based delivery systems. Many of these formulations demonstrate improved bioavailability, enhanced tissue targeting, and greater in vivo stability compared to the native compound. This review summarizes nanoformulations of the most promising and extensively studied TCM compounds to provide a reference for further research. Combining these natural compounds with nanotechnology-based delivery systems may further improve the clinical utility of these agents, in turn leading to more intensive research on traditional medicinal compounds.

Injectable Peptide Hydrogel Enables Integrated Tandem Enzymes' Superactivity for Cancer Therapy.

Elevation of the levels of reactive oxygen species and other toxic radicals is an emerging strategy to treat certain cancers by modulating the redox status of cancer cells. The biocatalytic upregulation of singlet oxygen by neutrophilic leukocytes should utilize robust enzymes and design carriers with protective microenvironment. Here, we utilize GOx-CPO as integrated tandem enzymes to in situ generate singlet oxygen, which could be not only for oxidative cross-linking of injectable hydrogel carriers but also for continuous tumor treatment by adjustable bioconversion of blood oxygen, glucose, and chloride ion. The tandem enzymes self-restrained within peptide hydrogel exhibited superactivity for upregulating singlet oxygen relative to free enzymes, which also avoids the diffusion of enzymes from tumor. This work will not only deepen the study of enzymes in biocatalysis but also offer an enzyme therapeutic modality for treating cancers.

Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy.

As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.

Enzymatic crosslinking to fabricate antioxidant peptide-based supramolecular hydrogel for improving cutaneous wound healing.

Peptide-based supramolecular hydrogels are promising scaffold materials and have been utilized in many fields. The mechanical properties of peptide hydrogels are usually enhanced by synthetic or natural polymers to expand their application scope. In this study, antioxidant supramolecular hydrogels based on feruloyl-modified peptide and glycol chitosan were fabricated via a mild laccase-mediated crosslinking reaction. A natural polysaccharide derivative, feruloyl glycol chitosan (GC-Fer), was used to enhance the mechanical properties of peptide hydrogels. Feruloyl groups were introduced into the gel matrix via covalent bonds, which endowed the hydrogels with inherent antioxidant properties. This was beneficial for their in vivo application via scavenging harmful free radicals existing in a cutaneous wound. Further in vivo experiments demonstrated that the feruloyl-containing antioxidant hydrogel can improve the cutaneous wound healing process. The regeneration process of mature epithelium and connective tissues was accelerated in a full-thickness skin defect model.

Controllable Growth of Core-Shell Nanogels via Esterase-Induced Self-Assembly of Peptides for Drug Delivery.

In this work, we developed an unexplored enzyme-responsive core-shell nanogel via the assembly of hydrogelators at the surface of silicon nanoparticles. The immobilized carboxylesterase at the surface of silicon nanoparticles can catalyse precursors into hydrogelators, self-assembling around the surface of silicon nanoparticles owing to its surface confinement effect. These novel phenomena can be confirmed by observation of their morphology and increased diameters through scanning electron microscopy, transmission electron microscopy and dynamic light scattering. Moreover, these resulting core-shell nanogels can achieve controlled growth of the gel layer by means of changing the concentrations of precursors. Because of their good biocompatibility, these nanogels can realize applications in enzyme-specific drug delivery as nanocarriers.