Cardiovascular disease (CVD)-related mortality continues to increase, imposing persistently high social and economic burdens. Accumulating evidences have indicated that plasma cholesterol concentration is closely related to the morbidity and prognosis of CVD. The balance of cholesterol metabolism has profound implication for preventing and decreasing CVD. Therefore, it is necessary to clarify the pathways and mechanisms of cholesterol metabolism in the human body. Both hepatobiliary pathway and transintestinal cholesterol excretion (TICE) pathway could clean out cholesterol through feces, but the treatment of cholesterol-lowering by targeting hepatobiliary pathway is not satisfactory, and aiming at the TICE pathway may be a more effective strategy. However, the specific mechanism of TICE remains largely unknown. Herein, this review summarizes the past and present understanding of TICE development history, put a special emphasis on the process and molecular mechanisms as well as the influence factor of TICE. Additionally, this article also predicts and discusses the potential mechanisms of candidate genes and non-coding RNAs that may mediate TICE. Furthermore, we discuss the emerging potential of nanocarrier-based delivery systems for targeted modulation of TICE, offering new possibilities for cholesterol-lowering therapies. This review may provide new strategies for promoting cholesterol elimination from body and reducing CVD risk, and provide a theoretical basis for the future development of TICE-targeted drugs.

Exosome applications in biomedicine have gained momentum in the last two decades, mainly due to their remarkable versatility. Exosomes are extracellular vesicles that carry diverse nucleic acids, proteins, lipids, enzymes, and growth factors, making them ideal for intercellular communication. Their surface can be engineered to express specific molecules and loaded with exogenous cargo such as drugs, nucleic acids, and therapeutic proteins. Exosomes also bear proteins and cell markers. Their immunocompetence initiation is also well established. Stem and immune cell exosomes have been extensively studied for their immunomodulatory effects in solid tumors, leukemia, cardiovascular diseases, diabetes, and inflammatory and rheumatic diseases, both in their natural and engineered forms.. Exosomes are majorly engineered via surface decoration by desired molecules, either by chemical methods or parent cells’ engineering to express molecules on their surface. For instance, CAR-cells isolated exosomes have been immensely investigated for various diseases therapies. Moreover, immunomodulating molecules loading on exosomes is a known method for exosome engineering aiming at specific disease therapy. In this review, we focus on the role of engineered exosomes in immune modulation therapy for various diseases and conditions, highlighting their intriguing potential in this field.

Bladder cancer (BC) exhibits limited responsiveness to conventional therapies such as intravesical immunotherapy and chemotherapy, alongside high recurrence rates and significant treatment costs. Recent advances in immunomodulatory nanomaterials offer promising solutions by enabling precise intravesical drug delivery, prolonged urothelial retention, and targeted modulation of the tumor immune microenvironment. Various nanoplatforms including liposomes, polymers, mesoporous materials and engineered bacteria have been developed to facilitate the co-delivery of chemotherapeutic agents and immunomodulators, induce immunogenic cell death (ICD), and enhance antigen presentation. Synergistic therapeutic strategies that integrate photodynamic, sonodynamic, photothermal and magnetic hyperthermia treatments, as well as novel regulated cell death pathways such as ferroptosis, cuproptosis and disulfidptosis, have demonstrated potential in overcoming immune resistance and eliciting robust antitumor immunity. Nevertheless, several key challenges remain, including biosafety concerns, limited tumor tissue penetration, inconsistencies in large scale production, and incomplete understanding of the interactions between nanomaterials and the immune system. Future progress will rely on the integration of artificial intelligence driven nanocarrier design, multi-omics-based immune profiling, organoid-based validation models, and intelligent manufacturing technologies. These innovations are expected to accelerate the clinical translation of safe, controllable, and personalized nanomedicine-based immunotherapies, ultimately driving a paradigm shift in the precision treatment of bladder cancer.

Circulating tumor cells (CTCs) significantly impact the overall survival and progression-free survival of cancer patients. However, the current strategies for CTC separation and enrichment are limited as they analyze only small-volume blood samples, which is insufficient to comprehensively profile the distribution of CTCs in the blood and eliminate them. To address this issue, we developed a peripheral blood CTC removal device (PBCRD) inspired by hemoperfusion. It comprises systems for CTC-capturing and returning purified blood into circulation. The CTC capturing system consists of antibody-modified functional microspheres (AFMPs), while the purified blood returning system includes a peristaltic circulation pump for clinical blood perfusion and catheters. The PBCRD can efficiently capture, enrich, and remove CTCs from peripheral circulation in real-time, effectively inhibiting their biodistribution. The high biocompatibility of AFMPs ensures that PBCRD is safe and does not cause injuries. Overall, this work provides a new class of ideas for the effective capture and removal of CTCs from the peripheral circulation, which is expected to be an effective strategy to assist in the clinical treatment of tumors and inhibit metastasis.

Inflammation plays a critical role in maintaining tissue homeostasis and facilitating repair, but dysregulated inflammation can lead to the development and progression of inflammatory diseases, posing a significant threat to human health. Inorganic nanomaterials, due to their unique physicochemical properties, have emerged as powerful tools for modulating the inflammatory microenvironment. This review discusses the potential of inorganic nanomaterials in addressing key inflammatory processes, including oxidative stress regulation, immune cell modulation, and the blockade of pro-inflammatory signaling pathways. We highlight strategies such as surface functionalization for targeted delivery, the design of nanostructures with antioxidant properties, and the controlled release of therapeutic gases, which together offer new avenues for precision inflammation therapy. Additionally, we explore the ability of these nanomaterials to influence immune responses, from macrophage polarization to the inhibition of inflammasome activation, and discuss their multifaceted roles in regulating the immune system. Despite promising preclinical results, challenges remain in terms of biosafety, long-term stability, and addressing the heterogeneous nature of the inflammatory microenvironment. Future efforts should focus on developing multifunctional nanoplatforms that can simultaneously target multiple inflammatory pathways, paving the way for more effective and personalized treatments of inflammatory diseases.

Effective mild-temperature photothermal therapy (MTPTT) requires photothermal agents with high photothermal conversion efficiency (PCE) and balanced fluorescence quantum yield to enable efficient tumor treatment while minimizing damage to surrounding healthy tissues. In this study, we designed donor–acceptor–donor structured dyes, 4,4’-((6,7-di(thiophen-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-bis(4-methoxyphenyl)aniline) (IT-STPA) and 4,4’-((6,7-di(furan-2-yl)-[1,2,5]thiadiazolo[3,4-g]quinoxaline-4,9-diyl)bis(thiophene-5,2-diyl))bis(N,N-bis(4-methoxyphenyl)aniline) (IT-OTPA), featuring furan-modified thiadiazolo-quinoxaline for near-infrared–II (NIR-II) fluorescence imaging and enhanced PCE. The furan and thiophene modifications promoted aggregation-induced emission, resulting in strong fluorescence emission (1 000–1 400 nm) while maintaining a high PCE of 48.5%. IT-OTPA was encapsulated into nanoparticles for improved aqueous dispersion and combined with the HSP70 inhibitor apoptozole (APZ) to form OTAPZ nanoparticles. The efficacy of this combination was evaluated both <i>in vitro</i> and <i>in vivo</i>, showing efficient tumor targeting and effective MTPTT under NIR laser irradiation. This study presents a promising approach for enhancing MTPTT through balanced photothermal and fluorescence properties, offering new possibilities for cancer treatment.

The treatment of multidrug-resistant bacteria is a difficult problem in clinical practice. These drug-resistant bacteria have reduced sensitivity to antibiotics, which contributes to the high incidence and mortality of bacterial infections worldwide. Photothermal therapy and chemodynamic therapy are advanced nanomaterial-based medical treatment methods and are widely used in tumor and antibacterial therapies due to their precision and rapidity. To overcome the limitations of conventional treatment for bacterial resistance, this study developed a near-infrared-II (NIR-II) responsive nanomaterial, a gold nanoframework coated with copper selenide (GNF@CS). This nanomaterial simultaneously triggers both chemodynamic therapy and photothermal therapy, while further promoting the chemodynamic process through <i>in-situ</i> heat generation. Ultimately, it shows significant antibacterial effects against both <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>, providing a new non-antibiotic-dependent treatment strategy for clinically relevant bacterial infections.