Engineered Platelet for Natural Killer Cell Activation to Inhibit Tumor Recurrence.

Natural killer (NK) cells offer profound advantages against tumor recurrence due to their unique immunological behavior. NK cell therapies associated with the antibody-dependent cell-mediated cytotoxicity (ADCC) effect have made remarkable progress while being limited by insufficient antibody binding and the exhausted state of NK cells in the postsurgical immunosuppressive microenvironment. Leveraging the adherence of PLT to tumor cells, we developed an exogenously implanted platelet (PLT)-based NK cell-driven system (PLT-IgG-IL15) to improve the identifiability of residual tumors with IgG antibody labeling for NK cells catching and engaging, which consequently restored the ADCC effect and promoted the recovery of their killing function.

Michael Addition-Based Neoadjuvant for Enhanced Cancer Immunotherapy.

Cancer immunotherapy suffers from inefficient antigen presentation owing to the limited endocytosis of antigen by dendritic cells (DCs) and dysfunction of DCs in the immunosuppressive tumor microenvironment (ITME). Here, we revealed that cinnamaldehyde-grafted polyethylenimine (PC) held the potential to serve as a neoadjuvant to modulate the above processes and thus potentiate immune responses. The PC neoadjuvant could capture the tumor antigen generated during chemotherapy to enhance the crosstalk between the antigen and DCs.

"Dominolike" Barriers Elimination with an Intratumoral Adenosine-Triphosphate-Supersensitive Nanogel to Enhance Cancer Chemoimmunotherapy.

Pathophysiological barriers in "cold" tumors seriously limit the clinical outcomes of chemoimmunotherapy. These barriers distribute in a spatial order in tumors, including immunosuppressive microenvironment, overexpressed chemokine receptors, and dense tumor mesenchyme, which require a sequential elimination in therapeutics. Herein, we reported a "dominolike" barriers elimination strategy by an intratumoral ATP supersensitive nanogel (denoted as B@PAC-PTX) for enhanced chemoimmunotherapy.

Reversing the PAI-1-induced fibrotic immune exclusion of solid tumor by multivalent CXCR4 antagonistic nano-permeator.

Fibrosis is one of the key factors that lead to the immune exclusion of solid tumors. Although degradation of fiber is a promising strategy, its application was still bottlenecked by the side effects of causing metastasis, resulting in the failure of immunotherapy. Here, we developed an antimetastatic polymer (HPA) for the delivery of chemo-drug and antifibrotic siPAI-1 to form the nano-permeator.

Laparoscopic fundoplication in treating refractory gastroesophageal reflux-related chronic cough: A meta-analysis.

Background: Gastroesophageal reflux-related chronic cough (GERC), is one common type of chronic cough. Drug treatment is effective for some GERC patients. But, there is refractory GERC (rGERC).

Engineered apoptotic bodies hitchhiking across the blood-brain barrier achieved a combined photothermal-chemotherapeutic effect against glioma.

Glioma as a highly lethal tumor is difficult to treat since the blood-brain barrier (BBB) restricts drug delivery into the brain. It remains a huge need for developing strategies allowing drug passage across the BBB with high efficacy. Herein, we engineered drug-loaded apoptotic bodies (Abs) loaded with doxorubicin (Dox) and indocyanine green (ICG) to cross the BBB for the treatment of glioma.

Redox modulation with a perfluorocarbon nanoparticle to reverse Treg-mediated immunosuppression and enhance anti-tumor immunity.

Tumor hypoxia and high glutathione (GSH) expression promote regulatory T cell (Treg) infiltration and maintain its immunosuppressive function, which significantly reduces the response rate of cancer immunotherapy. Here, we developed an immunomodulatory nano-formulation (FEM@PFC) to reverse Treg-mediated immunosuppression by redox regulation in the tumor microenvironment (TME). Oxygen carried in perfluorocarbon (PFC) was delivered to the TME, thus relieving the hypoxic condition and inhibiting Treg infiltration.

A Bio-Liposome Activating Natural Killer Cell by Illuminating Tumor Homogenization Antigen Properties.

Natural killer (NK) cell therapies, primarily based on chimeric antigen receptor NK cells (CAR-NK), have been developed and applied clinically for therapeutic treatment of patients with mid-to-late-stage tumors. However, NK cell therapy has limited efficacy due to insufficient antigen expression on the tumor cell surface. Here, a universal "illuminate tumor homogenization antigen properties" (ITHAP) strategy to achieve stable and controlled antigen expression on the surface of tumor cells using nanomedicine, thus significantly enhancing the immune recognizability of tumor cells, is described.

Pore forming-mediated intracellular protein delivery for enhanced cancer immunotherapy.

Directly delivering therapeutic proteins to their intracellular targets remains a great challenge. Here, we apply CD8 T cells to form pores on the tumor cells' plasma membranes, enabling perfusion of ribonuclease A (RNase A) and granzyme B into cells, therefore effectively inducing tumor apoptosis and pyroptosis by activating caspase 3 and gasdermin E pathways to potentiate the CD8 T cell-mediated immunotherapy. Then, RNase A, programmed cell death ligand 1 antibody, and a photothermal agent were further loaded into an injectable hydrogel to treat the low immunogenic murine breast cancer.

Therapeutic targeting of glutamate dehydrogenase 1 that links metabolic reprogramming and Snail-mediated epithelial-mesenchymal transition in drug-resistant lung cancer.

Acquired drug resistance and epithelial-mesenchymal transition (EMT) mediated metastasis are two highly interacting determinants for non-small-cell lung cancer (NSCLC) prognosis. This study investigated the common mechanisms of drug resistance and EMT from the perspective of metabolic reprogramming, which may offer new ideas to improve anticancer therapy. Acquired resistant cells were found to grow faster and have a greater migratory and invasive capacity than their parent cells.

Site-Specific Polyplex on CCR7 Down-Regulation and T Cell Elevation for Lymphatic Metastasis Blocking on Breast Cancer.

Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration.

Tumor-penetrating iron oxide nanoclusters for / dual mode MR imaging-guided combination therapy.

Emerging nanotheranostic systems have promoted the development of dual-mode imaging techniques (/-weighted MRI) to meet the increasing requirements of accurate personalized treatment for cancer. Nevertheless, slight tumor accumulation and poor penetration have limited the efficacy of dual-mode theranostic agents. Furthermore, under the premise of guaranteeing imaging capability, most current research studies hardly focused on optimizing theranostic agents to achieve considerable therapeutic effects.

Poly-antioxidants for enhanced anti-miR-155 delivery and synergistic therapy of metastatic breast cancer.

Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release.

Synergetic regulation of kupffer cells, extracellular matrix and hepatic stellate cells with versatile CXCR4-inhibiting nanocomplex for magnified therapy in liver fibrosis.

Hepatic stellate cell (HSC)-targeted delivery is an attractive strategy for liver fibrosis therapy, but the efficacy is hampered by poor delivery of nanomaterials and complicated microenvironments of the fibrotic liver. Here, we report a versatile CXCR4-inhibiting nanocomplex composed of polymeric CXCR4 antagonism (PAMD, PA), CLD (clodronate) and siPAI-1 (siRNA of plasminogen activator inhibitor-1) that surmounts multiple barriers to improve the outcome by co-regulating Kupffer cells (KCs), extracellular matrix (ECM) and HSCs. Upon encountering biological barriers, the nanocomplex exerted penetrating and targeting functions, efficiently overcoming KCs capture, ECM trapping and nonspecific recognition of HSCs, finally contributing to the enhanced HSCs uptake.

Glutathione Depletion-Induced Activation of Dimersomes for Potentiating the Ferroptosis and Immunotherapy of "Cold" Tumor.

The abundant glutathione (GSH) in "cold" tumors weakens ferroptosis therapy and the immune response. Inspired by lipids, we fabricated cinnamaldehyde dimers (CDC) into lipid-like materials to form dimersomes capable of depleting GSH and delivering therapeutics to potentiate the ferroptosis and immunotherapy of breast cancer. The dimersomes exhibited superior storage stability for over one year.

Crosslinked Protein Delivery Strategy with Precise Activity Regulation Properties for Cancer Therapy and Gene Editing.

Protein drugs hold tremendous promise for therapeutic applications due to their direct and superior pharmacological effects. However, protein drugs can be degraded in blood stream and unable to cross many physical barriers to exert therapeutic effect. Degradable synthetic crosslinking is a versatile strategy to enhance the stability of the nanoparticle in a complex physiological medium and is helpful to get through physical barriers.

"Attractive/adhesion force" dual-regulatory nanogels capable of CXCR4 antagonism and autophagy inhibition for the treatment of metastatic breast cancer.

Metastasis is refractory systemic disease resulting in low survival rate of breast cancer patients, especially in the late stage. The processes of metastasis are mainly initiated by strong "attractive force" from distant organs and deteriorated by weak "adhesion force" in primary tumor. Here, we reported "attractive/adhesion force" dual-regulatory nanogels (CQ-HF/PTX) for the precise treatment of both primary and metastasis of metastatic breast cancer.

In situ self-assembled peptide nanofibers for cancer theranostics.

Self-assembled nanofibers hold tremendous promise for cancer theranostics owing to their in situ assembly, spatiotemporal responsiveness, and diverse bioactivity. Herein, this review summarizes the recent advances of self-assembled peptide nanofibers and their applications in biological systems, focusing on the dynamic process of capturing cancer cells from the outside-in. (1) In situ self-assembly in response to pathological or physiological changes.

Metabolizable Near-Infrared-II Nanoprobes for Dynamic Imaging of Deep-Seated Tumor-Associated Macrophages in Pancreatic Cancer.

Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer.

Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio.

Background: The objective of this study was to investigate the relationship among hypersensitive C-reactive protein to albumin ratio (CAR), fibrinogen to albumin ratio (FAR), and the CURB-65 score for community-acquired pneumonia (CAP) severity.

Methods: Clinical data and laboratory indicators of 82 patients with CAP and 40 healthy subjects were retrospectively analysed. The relationship among CAR, FAR, and the severity of CAP was then analysed.

A rutin nanocrystal gel as an effective dermal delivery system for enhanced anti-photoaging application.

As a natural flavonoid compound, rutin could scavenge free radicals effectively to achieve remarkable antioxidant and anti-photoaging activity. Unfortunately, the extremely low water solubility of rutin often leads to the poor percutaneous permeability and unsatisfactory bioavailability, which has greatly restricted its clinical application. In this study, a novel freeze-dried rutin nanocrystal was developed to improve its saturation solubility, which was further redispersed in carbopol gel to formulate the targeted rutin nanocrystal gel (NC-gel) for enhanced transdermal delivery efficiency.

Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot.

Clinical investigations have shown that a nonimmunogenic "cold" tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor "hot." Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).