Magnetic-Responsive Semilifeform for Protecting Peritumoral T Lymphocytes and Precise Tumor Eradication.

Abstract

Anti-CD47 therapy restores macrophage-mediated phagocytosis to reverse the tumor immunosuppressive microenvironment (TIME). However, peritumoral (PT) T cells, which play an indispensable role in tumor eradication, also rely on CD47 for maintenance. The potential impact of anti-CD47 therapy on their maintenance remains unclear. In this study, we reveal that anti-CD47 therapy induces the removal of PT T cells by macrophages, followed by a reduction in the replenishment of intratumoral T cells, although the therapy reinvigorates the TIME and establishes a favorable milieu for immune responses. To address this contradiction, we developed a magnetically responsive semilifeform by equipping <i>E. coli</i>^minicell-CD47nb with a controllable separation cocoon composed of phase-change material and magnetic fluid. Under a constant magnetic field, the cocoon remains solid, shielding the anti-CD47 nanobody (CD47nb) and propelling the semilifeform to traverse PT regions without disturbing resident PT T cells. Upon reaching the tumor interior, an alternating magnetic field is applied to induce magnetic fluid heating, triggering a solid-to-liquid phase transition of the cocoon. The liquid-phase cocoon separates from the <i>E. coli</i>^minicell-CD47nb, exposing CD47nb to reeducate the TIME. This semilifeform resolves the therapeutic paradox of anti-CD47 therapy by achieving spatiotemporal-controlled CD47 blockade and enhancing therapeutic efficacy in both primary and distant tumors.