Combination therapy based on molecular drugs and therapeutic genes provides an effective strategy for malignant tumor treatment. However, effective gene and drug combinations for cancer treatment are limited by the widespread antagonism between therapeutic genes and molecular drugs. Herein, a calixarene‐embedded nanoparticle (CENP) is developed to co‐deliver molecular drugs and therapeutic genes without compromising their biological functions, thereby achieving interference‐free gene–drug combination cancer therapy. CENP is composed of a cationic polyplex core and an acid‐responsive polymer shell, allowing CENP loading and delivering therapeutic genes with improved circulation stability and enhanced tumor accumulation. Moreover, the introduction of carboxylated azocalix[4]arene, which is a hypoxia‐responsive calixarene derivatives, in the polyplex core endows CENP with the capability to load molecular drugs through the host–guest complexation as well as inhibit the interference between the drugs and genes by encapsulating the drugs into its cavity. By loading doxorubicin and a plasmid DNA‐based CRISPR interference system that targets miR‐21, CENP exhibits the significantly enhanced anti‐tumor effects in mice. Considering the wide variety of calixarene derivatives, CENP can be adapted to deliver almost any combination of drugs and genes, providing the potential as a universal platform for the development of interference‐free gene–drug combination cancer therapy.

n(DNase) exhibited great potential as a novel antibiotic adjuvant that overcomes biofilm-associated infections with the combinational use of antibiotics.

No abstract

The release of tumor‐associated antigens (TAAs) and their cross‐presentation in dendritic cells (DCs) are crucial for radio‐immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross‐presentation. Herein, an antigen‐capturing stapled liposome (ACSL) with a robust structure and bioactive surface is developed. The ACSLs capture and transport TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross‐presentation. l‐arginine encapsulated in ACSLs induces robust T cell‐dependent antitumor response and immune memory in 4T1 tumor‐bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing l‐arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies.

The accumulation of soluble β-amyloid aggregates (sAβs) is one of the main culprits in Alzheimer's disease (AD) progression, which can lead to synaptic dysfunction and subsequent neurodegeneration. Herein, we describe a nanoscavenger with novel structure that can cross the blood-brain barrier (BBB), accurately collect neurotoxic sAβs, and facilitate amounts of β-amyloid (Aβ) clearance. The nanoscavenger is composed of an Aβ-binding albumin nanoparticle surface-decorated with Immunoglobulin G (IgG) and brain-targeting peptide (PEGylated B6). During transport across the BBB, the nanoscavenger detaches PEGylated B6 and enters the brain. Then, the nanoscavenger competitively inhibits the formation of neurotoxic sAβs, and induces the coaggregation of preexistent sAβs, leading to the formation of nanoscavenger/Aβ coaggregates. Such aggregates are readily cleared by microglia via antibody-dependent cell-mediated phagocytosis (ADCP) even under an inflammatory environment in APP/PS1 mice. Our nanoscavenger demonstrates a disease-related biological processes, providing a new approach in nanomedicine development.