G-Quadruplex RNA Based PROTAC Enables Targeted Degradation of RNA Binding Protein FMRP for Tumor Immunotherapy.

Fragile X mental retardation protein (FMRP), an RNA binding protein (RBP), is aberrantly hyper-expressed in human tumors and plays an essential role in tumor invasion, metastasis and immune evasion. However, there is no small-molecule inhibitor for FMRP so far. In this study, we developed the first FMRP-targeting degrader based on PROteolysis TArgeting Chimera (PROTAC) technology and constructed a heterobifunctional PROTAC through linking a FMRP-targeting G-quadruplex RNA (sc1) to a von Hippel-Lindau (VHL)-targeting ligand peptide (named as sc1-VHLL).

Surgical tumor-derived nanoplatform targets tumor-associated macrophage for personalized postsurgical cancer immunotherapy.

Directly activating CD8 T cells within the tumor through antigen-presenting cells (APCs) hold promise for tumor elimination. However, M2-like tumor-associated macrophages (TAMs), the most abundant APCs in tumors, hinder CD8 T cell activation due to inefficient antigen cross-presentation. Here, we demonstrated a personalized nanotherapeutic platform using surgical tumor-derived galactose ligand-modified cancer cell membrane (CM)-coated cysteine protease inhibitor (E64)-loaded mesoporous silica nanoparticles for postsurgical cancer immunotherapy.