Ye Wu, Wencong Jia, Tianlai Xia, Jing Liao, Wenjin He, Huijing Wang, Wei Yang, Xinyue Dai, Wei Feng, Rachel K. O’Reilly, Zaizai Tong, Meihua YU, Yujie Xie, Yu Chen
Achieving precise spatiotemporal modulation of immunostimulatory effects remains a fundamental barrier in tumor immunotherapy, particularly in the context of limited tumor antigen exposure and an immunosuppressive microenvironment. Herein, we present a light-responsive “dynamic nanopatch” platform that addresses these challenges through morphology-directed and interface-programmed immunoactivation. Constructed from crystalline poly(ε-caprolactone) and integrated with photothermal conversion elements, the nanopatch undergoes a near-infrared (NIR)-triggered morphology-dynamic transition from a two-dimensional planar structure to a zero-dimensional spherical counterpart. This dynamic structural transformation enables programmable interactions with the cellular membrane, establishing a versatile nanointerface capable of the in situ regulation of cancer cell membrane integrity. Upon NIR irradiation, the nanopatch stably adheres to the tumor cell surface and initiates a cascade of adhesion, deformation, and internalization events. This process promotes localized mechanical stress and membrane perturbation, enhancing the release of tumor-associated antigens and damage-associated molecular patterns, which collectively initiate potent immunogenic cell death. Subsequent activation of antigen-presenting cells leads to robust adaptive immune engagement and amplified immune cell infiltration within the tumor microenvironment. This morphodynamic nanopatch offers a highly controllable strategy for cancer immunotherapy and a new paradigm for interface-programmed functionalities with broad implications for precision medicine, immunotherapy, and biomaterial engineering.