Membrane‐Bound Multimodal Plasmonic Transducers for Noninvasive, In Situ Monitoring and Control of CAR T Cells Against Heterogeneous Solid Tumors

ABSTRACT

Noninvasive monitoring and control of CAR T cells against heterogeneous solid tumors remain major challenges in understanding and improving treatment response. To address this, membrane‐bound plasmonic transducers, composed of plasmonically coupled gold nanospheres in an anisotropic framework, were developed for multimodal photoacoustic imaging and localized thermal modulation of CAR T cell activity. These transducers exhibit approximately 90% absorption efficiency and photostability under laser fluences exceeding 20 mJ cm ⁻² , delivering photoacoustic and thermal responses over multiple lasing cycles. Membrane‐bound transducers on CAR T cells thus enable photoacoustic and thermal responsiveness upon laser excitation without compromising key cellular functions. In heterogeneous HER2‐expressing breast tumor models, longitudinal photoacoustic imaging enabled prospective stratification of tumors based on early T cell trafficking, predicting responders versus nonresponders with high sensitivity and specificity. Moreover, transducer‐mediated thermal modulation of intratumoral CAR T cells engineered with thermogenetic circuits to secrete T cell engagers redirected cytotoxicity toward antigen‐negative tumors, overcoming antigen escape and consequently enhancing therapy. Taken together, we demonstrate a strategy to noninvasively monitor and control CAR T cells against heterogeneous solid tumors via membrane‐bound multimodal transducers.