Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions. Uptake of AuNRs causes reactive oxygen species accumulation and protein misfolding in the cell, leading to NSG formation. Physically, NSGs have a gel-like core and a liquid-like shell, influenced positively by HSP70 and negatively by HSP90 and the ubiquitin-proteasome system. AuNRs promote NSG assembly by interacting with G3BP1, reducing the energy needed for liquid–liquid phase separation (LLPS). NSGs impact cellular functions by affecting mRNA surveillance and activating Adenosine 5′-monophosphate (AMP)-activated protein kinase signaling, crucial for a cellular stress response. Our study highlights the role of LLPS in nanomaterial metabolism and suggests NSGs as potential targets for drug delivery strategies, advancing the field of nanomedicine.
Chemodynamic therapy (CDT) efficacy in the tumor microenvironment (TME) remains compromised. Inspired by the potential of fever-like heat to activate a redox-favorable microenvironment, mild photothermal therapy (mPTT) is expected to sensitize tumors to CDT, turning “redox-cold” tumors into “redox-hot” ones. Herein, an injectable gel engine (LMFT@SG-R) is meticulously constructed based on the co-encapsulation of R848 and β-lapachone (LAP)-loaded metal–organic framework-199 (MOF-199) within a lipidic gel reservoir with the unique ability of thermally reversible sol–gel phase transformation. With mPTT reprogramming TME, the custom-designed LMFT@SG-R can realize systemic redox homeostasis remodeling through mPTT-activated chemodynamic immunotherapy (MPCIT). Once reaching the TME, LMFT@SG-R quickly hydrates into solid gel and subsequently undergoes gel-to-sol transformation under mild NIR laser irradiation, resulting in on-demand release of LMFT and R848 for controllable CDT and immunostimulation. LMFT undergoes stepwise degradation for sequential release of Fe 3+ , Cu 2+ and LAP, which can promote ROS cascade amplification owing to the upregulation of HSP70/NQO1 axis upon mild hyperthermia, resulting in robust ICD effects and T lymphocytes infiltrations together with R848. Notably, the controllable immunostimulation can facilitate robust abscopal effects and prominent suppression of distal tumors. The well-designed LMFT@SG-R may represent an updated CDT catalyst with the highly-integrated gel engine for chained-cooperative MPCIT.
危险品化学品经营许可证（带存储）