Customizable metal-phenolic supraparticles based on rationally designed building blocks

Metal-phenolic networks (MPNs) as a versatile platform for particle engineering have been well developed due to their integrated benefits of both metal ions and phenolic molecules. However, the approaches to broaden their applications are limited due to the single-driving force from the coordination of these two components. Herein, we developed a universal approach to introducing programmable assembles into MPNs to form metal-phenolic supraparticles based on the rationally designed phenolic building blocks. These as-prepared building blocks can first assemble into primary nanoparticles driven by various controllable intermolecular interactions (i.e., metal-organic coordination, host-guest interaction, and hydrophobic interaction), followed by particle assembly with metal ions to coat on different templates. The introduction of multiple assembly modalities into phenolic building blocks enriches the functionalities of these metal-phenolic supraparticles, such as dual-pH responsibility, light-controllable permeability, and rapid fluorescence labeling of living cells. Our work provides a conceptual and practical paradigm for customizing MPNs with hierarchical structures by importing various assembly strategies via rationally designed phenolic building blocks

Systemic Tumor Suppression via Macrophage‐Driven Automated Homing of Metal‐Phenolic‐Gated Nanosponges for Metastatic Melanoma

Abstract Cell‐based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug‐loading with high accumulations in solid tumors. Herein, a tumor‐targeting cellular drug delivery system (MAGN) by surface engineering of tumor‐homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron‐tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the “ON‐OFF” gating effect of the polyphenol‐based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor‐targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications