MRNA-based drug development is revolutionizing tumor therapies by enabling precise cancer immunotherapy, tumor suppressor gene restoration, and genome editing. However, the success of mRNA therapies hinges on efficient delivery systems that can protect mRNA from degradation and facilitate its release into the cytoplasm for translation. Despite the emergence of lipid nanoparticles (LNPs) as a clinically advanced platform for mRNA delivery, the efficiency of endo/lysosomal escape still represents a substantial bottleneck. Here, we summarize the intracellular fate of mRNA-loaded LNPs, focusing on their internalization pathways and processing within the endo-lysosomal system. We also discuss the impact of endo-lysosomal processes on mRNA delivery and explore potential strategies to improve mRNA escape from endo-lysosomal compartments. This review focuses on molecular engineering strategies to enhance LNP-mediated endo/lysosomal escape by optimizing lipid composition, including ionizable lipids, helper lipids, cholesterol, and PEGylated lipids. Additionally, ancillary enhancement strategies such as surface coating and shape management are discussed. By comprehensively integrating mechanistic insights into the journey of LNPs within the endo-lysosome system and recent advances in lipid chemistry, this review offers valuable inspiration for advancing mRNA-based cancer therapies by enabling robust protein expression.

Bacterial infections are common diseases causing tremendous deaths in clinical settings. It has been a big challenge to human beings because of the antibiotics abuse and the newly emerging microbes. Photodynamic therapy (PDT) is a reactive oxygen species-based therapeutic technique through light-activated photosensitizer (PS). Recent studies have highlighted the potential of PDT as an alternative method of antibacterial treatment for its broad applicability and high efficiency. However, there are some shortcomings due to the low selectivity and specificity of PS. Growing evidence has shown that drug delivery nanoplatforms have unique advantages in enhancing therapeutic efficacy of drugs. Particularly, stimuli-responsive nanoplatforms, as a promising delivery system, provide great opportunities for the effective delivery of PS. In the present mini-review, we briefly introduced the unique microenvironment in bacterial infection tissues and the application of PDT on bacterial infections. Then we review the stimuli-responsive nanoplatforms (including pH-, enzymes-, redox-, magnetic-, and electric-) used in PDT against bacterial infections. Lastly, some perspectives have also been proposed to further promote the future developments of antibacterial PDT.