PDL1/HER2‐Targeted Lipid‐Encapsulated Oxygen Nanobubbles Combined with Photodynamic Therapy for HER2+ Breast Cancer Immunotherapy

• DOI: 10.1002/adhm.202400030
• Publication Date: 2024-08-08T05:37:24Z
• Authors: Jilai Tian; Shixiao Wan; Zhen Yang; Mengting Wang; Wenzhao Zhou; Guanqun Wo; Shuping Fu; Shiya Zheng; Gaoxin Zhou; Xiaomin Hu; Yichen Guo; Jun Guo
• Keywords: Immunogenic cell death

Abstract Programmed death (PD) 1/PD ligand 1 (PDL1) inhibitors are immune checkpoint (ICIs) that may facilitate HER2‐positive breast cancer treatment; however, their clinical efficacy remains elusive. Oxygen‐enhanced photodynamic therapy (PDT) increases immunogenic cell (ICD), providing a promising strategy to render the tumor microenvironment more sensitive ICIs. Lipid‐encapsulated oxygen nanobubbles (Lipo‐NBs‐O 2 ) obtained using (NBs) water for delivery in vivo can enhanced PDT. Here, dual‐receptor targeted Lipo‐NBs‐O (DRT@Lipo‐NBs‐O is prepared by modifying with anti‐PDL1 scFv and fusion protein anti‐HER2 scFv‐tandem‐repeat cytochrome c (anti‐HER2‐nCyt ). Copper phthalocyanine photosensitizer (PS). DRT@Lipo‐PS‐NBs‐O plus near‐infrared irradiation leads robust ICD induction, increasing DC activation CD8 + T‐cell numbers. Modification improves distribution of plays ICI role, invigorating T cells boosting effects immunotherapy. Oxygen supplied through reduces P‐glycoprotein expression. Enhanced PDT Cyt cause death, thereby reducing burden. Under dual receptor targeting laser local irradiation, become subject combination PDT, ICD, ICIs, apoptosis; this effectively suppresses growth metastasis. affords multidrug alleviate cancer.