Strategies for functionalizing diverse tetrahedral framework nucleic acids (tFNAs) have been extensively explored since the first successful fabrication of tFNA by Turberfield. One-pot annealing of at least four DNA single strands is the most common method to prepare tFNA, as it optimizes the cost, yield, and speed of assembly. This review concentrates on four key merits of tFNAs and their potential for biomedical applications. The natural ability of tFNA to scavenge reactive oxygen species, along with remarkable enhancement in cellular endocytosis and tissue permeability based on its appropriate size and geometry, promotes cell-material interaction to direct or probe cell behavior, especially to treat inflammatory and degenerative diseases. Moreover, the structural programmability of tFNA enables the development of static tFNA-based nanomaterials via engineering of functional oligonucleotides or therapeutic molecules, and dynamic tFNAs via attachment of stimuli-responsive DNA apparatuses, leading to potentially applications in targeted therapies, tissue regeneration, antitumor strategies, and antibacterial treatment. Although there are impressive performance and significant progress, challenges and prospects of functionalizing tFNA-based nanostructures are still indicated in this review. This article is protected by copyright. All rights reserved 

Functionalizing Framework Nucleic‐Acid‐Based Nanostructures for Biomedical Application

A Mg2+/polydopamine composite hydrogel for the acceleration of infected wound healing

Copper-based metal-organic frameworks for biomedical applications.

Biofilm microenvironment-responsive nanoparticles for the treatment of bacterial infection

Photo-enhanced upcycling H2O2 into hydroxyl radicals by IR780-embedded Fe3O4@MIL-100 for intense nanocatalytic tumor therapy.

Improving the deep penetration of nanoparticles and realizing the combination of chemotherapy and immunotherapy have become a promising strategy for cancer treatment. Herein, a nuclear-targeted tetrahedral DNA nanostructure (NLS-TDNs, NT) was synthesized to construct matrix metalloproteinase (MMP-2) sensitive hydrogels as delivery vehicles with co-loaded disulfide cross-linked polyethyleneimine (PSP)/nuclear-targeted tetrahedral DNA (NLS-TDNs, NT)/doxorubicin (DOX) nanoparticles (NPs) (PSP/NT/DOX NPs and PNT/DOX NPs) and an immune adjuvant imiquimod (R837) to realize a combination of chemotherapy and immunization for metastatic breast cancer. Due to the membrane-breaking ability of the PNT/DOX NPs, the nanoparticles could effectively achieve deep penetration into tumor tissues, and the in situ generation of tumor-associated antigens by PNT/DOX elicited a strong immune response in the presence of R837, achieving a chemo-immune combination therapy of breast cancer, inducing the maturation of dendritic cells (DCs) and secretion of related cytokines, such as interleukin-6 (IL-6), interleukin-12 (IL-12p70) and tumor necrosis factor (TNF-α) in vitro. The combination significantly promoted the proportions of cytotoxic T cells (CD8+ CTL) and cytotoxic T cells/regulatory T cells (CD8+ CTL/Treg) (5.52% and 11.46%, respectively) and the secretion of cytokines, which cooperatively eradicated primary tumor growth (the tumor growth inhibition (TGI) value was 78.3%) and inhibited the tumor from metastasizing effectively in vivo. Our study provided the basis for activating the antitumor immune system to realize chemo-immunotherapy and tumor metastasis therapy.

In situ injection of dual-delivery PEG based MMP-2 sensitive hydrogels for enhanced tumor penetration and chemo-immune combination therapy

Diabetes mellitus has become one of the most challenging public health problems today. There are still various deficiencies that remain in existing therapeutic drugs. With increasing prevalence and mortality rates, more effective therapeutic agents are required for treatment clinically. As a kind of polyphenol and as a natural product, mangiferin has numerous pharmacological and excellent effects. In this review, the underlying mechanisms of mangiferin on diabetes mellitus and complications will be summarized. Moreover, mangiferin belongs to the BSC IV class and the clinical application and development of mangiferin are limited due to its poor aqueous solubility and fat solubility as well as low bioavailability. Our review also elaborated on improving the solubility of mangiferin by changing the dosage form and introduced the existing results, which hope to provide useful reference for mangiferin for further treating diabetes. In conclusion, mangiferin might be a potential adjuvant therapy for the treatment of diabetes mellitus and complications in the future.

The management of diabetes mellitus by mangiferin: advances and prospects.

Reduction-sensitive polymeric micelles as amplifying oxidative stress vehicles for enhanced antitumor therapy.

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In situ injection of dual-delivery PEG based MMP-2 sensitive hydrogels for enhanced tumor penetration and chemo-immune combination therapy

The management of diabetes mellitus by mangiferin: advances and prospects.

Reduction-sensitive polymeric micelles as amplifying oxidative stress vehicles for enhanced antitumor therapy.