Novel Anti-Trop2 Nanobodies Disrupt Receptor Dimerization and Inhibit Tumor Cell Growth.

Trop2 (trophoblast cell-surface antigen 2) is overexpressed in multiple malignancies and is closely associated with poor prognosis, thus positioning it as a promising target for pan-cancer therapies. Despite the approval of Trop2-targeted antibody-drug conjugates (ADCs), challenges such as side effects, drug resistance, and limited efficacy persist. Recent studies have shown that the dimeric forms of Trop2 are crucial for its oncogenic functions, and the binding epitopes of existing Trop2-targeted drugs lie distant from the dimerization interface, potentially limiting their antitumor efficacy.

Biointerface mineralization generates ultraresistant gut microbes as oral biotherapeutics.

Despite the fact that oral microecologics are effective in modulating the gut microbiome, they always suffer from multiple insults during the journey from manufacture to arrival at the intestine. Inspired by the protective mechanism of mineralization, we describe a cytocompatible approach of biointerface mineralization that can generate an ultraresistant and self-removable coating on bacterial surface to solve these challenges. Mineral coating endows bacteria with robust resistances against manufacture-associated oxygen exposure, ultraviolet irradiation, and 75% ethanol.

Recent advances in bacteria-mediated cancer therapy.

Cancer is among the leading cause of deaths worldwide. Although conventional therapies have been applied in the fight against the cancer, the poor oxygen, low extracellular pH, and high interstitial fluid pressure of the tumor microenvironment mean that these treatments fail to completely eradicate cancer cells. Recently, bacteria have increasingly been considered to be a promising platform for cancer therapy thanks to their many unique properties, such as specific tumor-targeting ability, high motility, immunogenicity, and their use as gene or drug carriers.

Block Co-PolyMOC Micelles and Structural Synergy as Composite Nanocarriers.

Conventional micelles of amphiphilic block copolymers (BCPs) disassemble into individual polymer chains upon dilution to a critical concentration, which causes the premature release of the encapsulated drugs and reduces the drug's bioavailability. Here, by integrating the emerging metal-organic cage (MOC) materials with BCPs, we introduce a new type of composite micellar nanoparticles, block co-polyMOC micelles (or BCPMMs), that are self-assembled in essence yet remarkably stable against dilution. BCPMMs are fabricated a stepwise assembly strategy that combines MOCs and BCPs in a well-defined, unimolecular core-shell structure.

Proteolysis-targeting chimaeras (PROTACs) as pharmacological tools and therapeutic agents: advances and future challenges.

Proteolysis-targeting chimaeras (PROTACs) have been developed to be an emerging technology for targeted protein degradation and attracted the favour of academic institutions, large pharmaceutical enterprises, and biotechnology companies. The mechanism is based on the inhibition of protein function by hijacking a ubiquitin E3 ligase for protein degradation. The heterobifunctional PROTACs contain a ligand for recruiting an E3 ligase, a linker, and another ligand to bind with the protein targeted for degradation.

Biomimetic Nanoparticles Enabled by Cascade Cell Membrane Coating for Direct Cross-Priming of T Cells.

Despite the activation of T lymphocytes by antigen-presenting cells being responsible for eliciting antigen-specific immune responses, their crosstalking suffers from temporospatial limitations and endogenous influencing factors, which restrict the generation of a strong antitumor immunity. Here, cascade cell membrane coating is reported to prepare biomimetic nanoparticles (BNs) that can manipulate the cross-priming of T cells. BNs are obtained from coating nanoparticulate substrates with cell membranes extracted from dendritic cells (DCs) that are pre-pulsed with cancer cell membrane-coated nanoparticles.

Aptamer-assisted tumor localization of bacteria for enhanced biotherapy.

Despite bacterial-mediated biotherapies have been widely explored for treating different types of cancer, their implementation has been restricted by low treatment efficacy, due largely to the absence of tumor-specific accumulation following administration. Here, the conjugation of aptamers to bacterial surface is described by a simple and cytocompatible amidation procedure, which can significantly promote the localization of bacteria in tumor site after systemic administration. The surface density of aptamers can be easily adjusted by varying feed ratio and the conjugation is able to increase the stability of anchored aptamers.

Combining anti-PD-1 antibodies with Mn-drug coordinated multifunctional nanoparticles for enhanced cancer therapy.

Immune checkpoint blockade therapy, particularly the use of engineered monoclonal antibodies against programmed cell death protein 1 (α-PD1) for activating T cells to kill cancer cells, becomes an effective strategy for cancer treatment. Despite its durable clinical responses, the modest response rates largely restrict the extensive implementation of this approach. Here, a combination of chemotherapy and photodynamic therapy to augment antitumor responses of α-PD1 has been achieved by core-shell metal ion-drug nanoparticles.

Enhancing anti-PD-1 Immunotherapy by Nanomicelles Self-Assembled from Multivalent Aptamer Drug Conjugates.

A tumor-targeting enhanced chemotherapy, enabled by aptamer-drug conjugate nanomicelles, is reported that boosts antitumor immune responses. Multivalent aptamer drug conjugate (ApMDC), an amphiphilic telodendrimer consisting of a hydrophilic aptamer and a hydrophobic monodendron anchored with four anticancer drugs by acid-labile linkers, was designed and synthesized. By co-self-assembly with an ApMDC analogue, in which aptamer is replaced with polyethylene glycol, the surface aptamer density of these nanomicelles can be screened to reach an optimal complementation between blood circulation and tumor-targeting ability.

Organic Semiconductors for Photothermal Therapy and Photoacoustic Imaging.

In recent years, semiconducting polymer nanoparticles (SPNs) have been attracting considerable attention because of their outstanding characteristics such as higher light and thermal stability. They are widely used in fields of biomedicine such as photoacoustic (PA) imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). PAI, a new imaging modality based on PA effects, shows great promise in biomedical applications.

Using ZIF-8 as stationary phase for capillary electrophoresis separation of proteins.

Recently, the separation of proteins has received much attention, although many techniques require expensive instrumentation and trained analysts. In this work, a low-cost, effective, and environmental friendship capillary electrophoresis (CE) for proteins separation was first time introduced. The ZIF-8 with outstanding properties of large surface area, and accessible tunnels and cages were coated the inner surface of silica capillary as a separation media by electrostatic interaction.

A smart thermo- and pH-responsive microfiltration membrane based on three-dimensional inverse colloidal crystals.

In this paper, a thermo- and pH-responsive microfiltration membrane was prepared based on three-dimensional (3D) inverse colloidal crystals (ICC). To manufacture the smart ICC membrane, the typical thermo-responsive N-isopropylacrylamide (NIPAM) and pH-responsive methacrylic acid (MAA) were polymerized inside silica colloidal crystals. The smart ICC membranes were characterized by SEM, IR and contact angle measurements.