Smartphone-ManipulatedMild-Temperature PhotothermalControl of the TfR-LYTAC Platform for Tumor Treatment

A lysosome-targeting chimera (LYTAC) offers a novel strategy for degrading extracellular proteins previously considered to be undruggable by hijacking the lysosomal degradation system. However, clinical use of LYTAC has been limited due to the potential for uncontrolled degradation and systemic toxicity. Based on our previously developed genetically encoded TfR-LYTAC, here, we introduce a photothermal-inducible switch in the engineered bacterium to enable spatiotemporal expression of TfR-LYTAC. We also developed precise photothermal systems to control LYTAC expression via cellphone manipulation to avoid burns of normal tissues, especially the skin, caused by intense laser light. The engineered bacterium exhibited significant tumor-suppressing effects upon exposure to the phone-manipulated laser in both subcutaneously transplanted melanoma and colon tumor models with no skin damage to the mice. Our approach enables LYTAC precision medicine and provides a generalizable platform for developing light-driven LYTAC. Our study provides a platform for outpatient or home treatment and is a further step for telemedicine.