Synergistic Effects of Polycationic and Polyfluorinated Functionalities for Efficient Intracellular Protein Delivery

Biomacromolecules, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Intracellular protein therapy is a promising strategy in biologics, including vaccine development, gene editing, and cancer therapeutics. However, protein-based drug delivery remains significant challenge, particularly penetrating cell barriers to reach intracellular targets. Inspired by transport adjuvants, we designed series of polymeric vectors achieve efficient functional trafficking with low cytotoxicity. With an adequate combination guanidinium fluorocarbon functionalities, synergistic improvement achieved terms both high cellular toxicity. The observed outcomes highlight new opportunities for vehicle optimizations biologics.

Language: Английский

A Dynamic Deferoxamine Polymer with Exceptional Performance in Mitochondrial Iron Depletion and Cytosolic Protein Delivery

Small, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract Deferoxamine (DFO) is an FDA‐approved naturally occurring iron chelator commonly used to treat transfusion‐induced overload. The abundant and flexible hydroxamic acid groups in DFO enable exceptional binding capacity high protein via hydrogen bonding interactions. However, the applications of sequester intracellular deliver proteins inside cells are limited due poor membrane‐permeability. Herein, fabrication a dynamic polymer proposed achieve robust delivery efficient mitochondrial depletion. Specifically, grafted onto polycatechol scaffold catechol‐boronate chemistry. obtained shows capacity, formed complexes show resistance toward serum proteins. It effectively delivers various cargo into cytosol treated with maintained bioactivity. In addition, cells, released efficiently depletes iron, which significantly inhibits oxidative phosphorylation glycolysis. Remarkable synergistic cytotoxic effects achieved when loaded toxic This study provides general strategy for facile preparation bioactive delivery, designed can be promising carrier therapeutics cancer.

Language: Английский

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

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract 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 native proteins. In this study, design synthesis protein nanocapsules (NCs) that achieve lung‐specific are reported. These NCs synthesized through surface modification process involves coating with functional monomers cross‐linkers, followed by situ polymerization create protective shell on tailored chemistry. This approach preserves integrity significantly enhances efficiency specificity. Notably, it is shown protein@NC guanidine‐rich surfaces exhibit exceptional lung‐targeting capabilities. likely attributed formation vitronectin‐rich corona, which facilitates receptor‐mediated endocytosis lung cells. The platform effectively delivers various proteins, such as ovalbumin, antigen‐presenting cells (APCs) lung, thereby enhancing antigen presentation offering promising strategy cancer immunotherapy. findings provide significant advancement tissue‐specific hold potential targeted

Language: Английский