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 drugloading 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.

Nanostructured single-atom catalysts derived from natural building blocks

“…183 Furthermore, the metal-driven coordination of phenolic moieties also facilitates the interfacial assembly of colloidal building blocks on the secondary substrates. This polyphenol-based modular approach provides a versatile platform for the construction of complex functional supraparticles, 184,185 therapeutically engineered cells, 186,187 and photo-driven biohybrids for chemical production. 188 Polyphenols are promising precursors for the preparation of CS-SACs due to their rich catechol and/or galloyl groups in structure and low price.…”

Magnetic Control of Nonmagnetic Living Organisms

“…Hence, nature provides a diverse range of components for the design of “living devices” with varying degrees of cognition and capability to perform biological functions. While the interest in exploiting the functional advantages of biological colloids is growing, − microrobotics based on living organisms faces a grand challengethe need for a versatile tool for the precise spatial manipulation of nonmagnetic living organisms.…”

Metal‐Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy

“…For example, we have previously demonstrated that MPNs can form biomimetic nanocloaks on the surface of individual bacteria, [24] yeast, [25] and mammalian cells. [26,27] Importantly, MPN coatings can also encapsulate various proteins, polysaccharides, and other functional cargos, due to their high affinity with biomolecules. [28][29][30] MPNs thereby exhibit the potential to preserve all the signaling and recognition biomolecules once cloaked on cancer cells.…”