(236) pH-Sensitive Zinc-Zoledronate Inhalation Therapy for Macrophage Modulation in Lung Cancer

Introduction: Lung cancer causes over 1.7 million deaths yearly (1). While immune checkpoint inhibitors improve survival, they often cause irAEs, leading to treatment discontinuation (2). Tumor-associated macrophages (TAMs) are key in lung tumors, with M2 promoting growth and M1 showing anti-tumor effects (3). Zoledronic acid (ZA) can reprogram TAMs but is limited by off-target toxicity (4). Inhalation delivers drugs directly to tumors, reducing systemic exposure and irAEs. This study develops a pH-sensitive zinc-zoledronate (Zn-ZA) inhalation to repolarize TAMs and improve efficacy.