Synthetic Nanocapsules with Tailored Surface Chemistry for Lung-Specific Protein Delivery and Cancer Immunotherapy.

Efficient delivery of therapeutic proteins remains a major challenge in developing effective immunotherapies and treatments for genetic disorders due to the limited tissue targeting capability of native proteins. In this study, the design and synthesis of protein nanocapsules (NCs) that achieve lung-specific delivery of therapeutic proteins are reported. These NCs are synthesized through a surface modification process that involves coating protein with functional monomers and cross-linkers, followed by in situ polymerization to create a protective shell on the protein surface with tailored surface chemistry.

Polyphenol-Assisted Biomineralization of Metal-Organic Framework Nanoparticles for Precision Delivery of Therapeutic Proteins to Cancer Cells.

The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8).

Delivering on Cell-Selective Protein Degradation Using Chemically Tailored PROTACs.

PROTACs (Proteolysis-Targeting Chimeras) have emerged as a groundbreaking class of chemical tools that facilitate the degradation of target proteins by leveraging the ubiquitin-proteasome system (UPS). However, the effective utilization of PROTACs in chemical biology studies and therapeutics encounters significant challenges when it comes to achieving cell-selective protein degradation and in vivo applications. This review article aims to shed light on recent advancements in the development of Pro-PROTACs, which exhibit controlled protein degradation capabilities in response to external stimuli or disease-related endogenous biochemical signals.

Intracellular Delivery of Glutathione Peroxidase Degrader Induces Ferroptosis In Vivo.

Ferroptosis is a new form of regulated, non-apoptotic cell death driven by iron-dependent phospholipid peroxidation. Its therapeutic potential is however, greatly limited by the low efficiency of regulating cell ferroptosis in vivo. Herein, we report a PROTAC-based protein degrader that depletes endogenous glutathione peroxidase 4 (GPX4) and induces cancer cell ferroptosis.

Hierarchical Self-assembly of Discrete Metal-Organic Cages into Supramolecular Nanoparticles for Intracellular Protein Delivery.

Hierarchical self-assembly (HAS) is a powerful approach to create supramolecular nanostructures for biomedical applications. This potency, however, is generally challenged by the difficulty of controlling the HAS of biomacromolecules and the functionality of resulted HAS nanostructures. Herein, we report a modular approach for controlling the HAS of discrete metal-organic cages (MOC) into supramolecular nanoparticles, and its potential for intracellular protein delivery and cell-fate specification.

Spatiotemporal Delivery of CRISPR/Cas9 Genome Editing Machinery Using Stimuli-Responsive Vehicles.

Recent innovations in genome editing have enabled the precise manipulation of the genetic information of mammalians, and benefitted the development of next-generation gene therapy. Despite these advances, several barriers to the clinical translation of genome editing remain, including the intracellular delivery of genome editing machinery, and the risk of off-target editing effect. Here, we review the recent advance of spatiotemporal delivery of CRISPR/Cas9 genome editing machinery, which is composed of programmable Cas9 nuclease and a single-guide RNA (sgRNA) using stimuli-responsive nanoparticles.