A Smart DNA Nanoassembly Containing Multivalent Aptamers Enables Controlled Delivery of CRISPR/Cas9 for Cancer Immunotherapy

CRISPR/Cas9 system is promising for the reversal of tumor immunosuppression in immunotherapy, but the controlled delivery of CRISPR/Cas9 remains challenging. Herein, the study reported a smart DNA nanoassembly containing multivalent aptamers, realizing the controlled delivery of Cas9/sgRNA ribonucleoprotein (RNP) for enhanced cancer immunotherapy. A single-stranded DNA complementary to sgRNA in the Cas9/sgRNA RNP can initiate a cascade-clamped hybridization chain reaction (C-HCR) to wrap the Cas9/sgRNA RNP up in the DNA nanoassembly. After selective internalization of DNA nanoassembly by cancer cells, Cas9/sgRNA RNP is released to cytoplasm in response to endogenous RNase H and enters the nuclei to knock out β-catenin. The expression of the programmed death-ligand one gene is effectively suppressed, and the immunosuppressive tumor microenvironment is reprogrammed. Meanwhile, the migration of cancer cells is inhibited, and the apoptosis of cancer cells is promoted. In a breast cancer mouse model, the administration of DNA nanoassembly effectively increased the infiltration of CD8⁺ T cells, eventually achieving high therapeutic efficacy.     

Advances in Chemically Powered Micro/Nanorobots for Biological Applications: A Review

Micro/nanorobots (MNRs) are capable of autonomous motion, breaking through the limitations of traditional passive transport of nanocarriers. Among them, chemically driven MNRs are the earliest MNRs studied and have received extensive attention from researchers. This review first focuses on the material properties, preparation, driving forms, and mechanisms of chemically driven MNRs. The current status of research on chemically driven MNRs in biomedicine is summarized for various biological applications (drug delivery, diagnostics, anti-inflammatory, antibacterial, and disease treatment). In terms of biosafety, possible safety issues are analyzed in the context of chemically driven microrobotic applications in terms of three aspects: component characteristics, chemical engines and biological environment. Finally, the challenges and possible future directions of chemically driven MNRs are presented.