In this regard, Tu et al. developed a weak-acidity-responsive nanoparticle for efficient delivery of cyclin-dependent kinase 5-targeting CRISPR-Cas9 (to suppress PD-L1 expression on tumor cells [132]) and paclitaxel (to trigger anti-tumor immune responses) to the tumor site, and thereby succeeded to exchange tumor microenvironment from “cold” to “hot” and to inhibit tumor growth in melanoma and colorectal cancer mice models [133]. This evidence concerns the gene CDK5 and neoplasm.