Current TB treatment regimens are hindered by drug resistance, numerous adverse effects, and long treatment durations, highlighting the need for ‘me-better’ treatment regimens. Host-directed therapy (HDT) has gained recognition as a promising approach in TB treatment. It allows the repurposing of existing drugs approved for other conditions and aims to enhance the effectiveness of existing anti-TB therapies, minimize drug resistance, decrease treatment duration, and adverse effects. By modulating the host immune response, HDT ameliorates immunopathological damage and improves overall outcomes by promoting autophagy, antimicrobial peptide production, and other mechanisms. It holds promise for addressing the challenges posed by multiple and extensively drug-resistant Mycobacterium tuberculosis strains, which are increasingly difficult to treat using conventional therapies. This article reviews various HDT candidates, including repurposed drugs, explores their underlying mechanisms such as autophagy promotion and inflammation reduction, while emphasizing their potential to improve TB treatment outcomes and outlining future research directions.

Light-activated tumor therapy (photodynamic therapy, gene therapy, immunotherapy, chemo-therapy and integrated therapy) based on UCNPs and the corresponding mechanisms.

The application of nMOFs to antitumor therapy, including drug delivery strategies, photodynamic therapy (PDT), photothermal therapy (PTT), and combination therapy, is presented.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a serious global public health threat. Due to the high incidence of adverse reactions associated with conventional treatment regimens, there is an urgent need for better alternative therapies. CpG oligodeoxynucleotides (CpG ODNs) are synthetic oligodeoxyribonucleotide sequences. They can induce a Th1-type immune response by stimulating Toll-like receptors (TLRs) in mammalian immune cells, thus killing Mtb. However, due to the negative charge and easy degradation of CpG ODNs, it is necessary to deliver them into cells using nanomaterials. PCN-224 (hereinafter referred to as PCN), as a metal–organic framework based on zirconium ions and porphyrin ligands, not only has the advantage of high drug loading capacity, but also the porphyrin molecule in it is a type of photosensitizer, which allows these nanocomposites to play a role in photodynamic therapy (PDT) while delivering CpG ODNs. In addition, since Mtb mainly exists in macrophages, targeting anti-TB agents to macrophages is helpful to improve the anti-TB effect. Phosphatidylserine (PS) is a biological membrane phospholipid that is normally found on the inner side of cell membranes in, for example, plant and mammalian cells. When apoptosis occurs, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, displaying a specific “eat-me” signal that can be recognized by specific receptors on macrophages. Therefore, we can use this macrophage-targeting property of PS to construct bio-inspired targeted drug delivery systems. In this study, we constructed PCN-CpG@PS nanocomposites. PCN-CpG@PS, combining PDT and immunotherapy, is designed to target macrophages at the site of a lesion and kill latent Mtb. We physically characterized the nanocomposites and validated their bactericidal ability in vitro and their ability to stimulate the immune system in vivo. The results demonstrated that the targeted nanocomposites have certain in vitro antituberculosis efficacy with good safety.

A metal–organic framework-based nanotheranostic system was fabricated to achieve the capabilities of tumor-targeting, real-time monitoring of pH-responsive drug release and combined chemo-photothermal therapy.

The lack of precise spatiotemporal gene modulation and therapy impedes progress in medical applications. Herein, a 980 nm near‐infrared (NIR) light‐controlled nanoplatform, namely URMT, is developed, which can allow spatiotemporally controlled photodynamic therapy and trigger the enzyme‐activated gene expression regulation in tumors. URMT is constructed by engineering an enzyme‐activatable antisense oligonucleotide, which combined with an upconversion nanoparticle (UCNP)‐based photodynamic nanosystem, followed by the surface functionalization of triphenylphosphine (TPP), a mitochondria‐targeting ligand. URMT allows for the 980 nm NIR light‐activated generation of reactive oxygen species, which can induce the translocation of a DNA repair enzyme (namely apurinic/apyrimidinic endonuclease 1, APE1) from the nucleus to mitochondria. APE1 can recognize the basic apurinic/apyrimidinic (AP) sites in DNA double‐strands and perform cleavage, thereby releasing the functional single‐strands for gene regulation. Overall, an augmented antitumor effect is observed due to NIR light‐controlled mitochondrial damage and enzyme‐activated gene regulation. Altogether, the approach reported in this study offers high spatiotemporal precision and shows the potential to achieve precise and specific gene regulation for targeted tumor treatment.