PD-L1-Targeting Biomimetic Photoresponsive Thermosensitive Liposomes for Triple-Negative Breast Cancer.

Peptide-based therapeutic strategies offer considerable potential for tumor immunotherapy but suffer from poor systemic bioavailability, rapid plasma clearance, and limited tumor-targeting efficiency. To address these challenges, a biomimetic, photothermal-responsive liposomal delivery system was developed that enables precise delivery of immunotherapeutic peptides while enhancing the synergistic effects of photothermal therapy. This system enhances peptide stability through fluorination, disrupts post-translational modifications of PD-L1, and promotes its degradation, thereby amplifying the anti-tumor immune response.

Hepatic micropeptide modulates mitochondrial RNA processing machinery in hepatocellular carcinoma.

Micropeptides, originating from noncanonical translation, represent novel biomolecules with critical roles in tissue homeostasis and cancer development. However, the proteomic landscape and functional mechanisms of micropeptides in hepatocellular carcinoma (HCC) remain largely elusive. By employing a newly devised ultrafiltration tandem mass spectrometry assay, we identified an abundance of micropeptides in clinical HCC samples.

Comprehensive discovery and functional characterization of the noncanonical proteome.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs.

LncRNA LINK-A Remodels Tissue Inflammatory Microenvironments to Promote Obesity.

High-fat diet (HFD)-induced obesity is a crucial risk factor for metabolic syndrome, mainly due to adipose tissue dysfunctions associated with it. However, the underlying mechanism remains unclear. This study has used genetic screening to identify an obesity-associated human lncRNA LINK-A as a critical molecule bridging the metabolic microenvironment and energy expenditure in vivo by establishing the HFD-induced obesity knock-in (KI) mouse model.

LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation.

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA (lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer (TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1 (PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis.

Advances in modification and delivery of nucleic acid drugs.

Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers.

A novel multifunctional gold nanorod-mediated and tumor-targeted gene silencing of GPC-3 synergizes photothermal therapy for liver cancer.

Tumor-specific targeted delivery is a major obstacle to clinical treatment of hepatocellular carcinoma (HCC). Here we have developed a novel multi-functional nanostructure GAL-GNR-siGPC-3, which consists of Galactose (GAL) as the HCC-targeting moiety, golden nanorods (GNR) as a framework to destroy tumor cells under laser irradiation, and siRNA of Glypican-3 (siGPC-3) which induce specifically gene silence of GPC-3 in HCC. Glypican-3 (GPC-3) gene is highly associated with HCC and is a new potential target for HCC therapy.

Silencing IDO2 in dendritic cells: A novel strategy to strengthen cancer immunotherapy in a murine lung cancer model.

While dendritic cell (DC)‑based immunotherapy has achieved satisfactory results in animal models, its effects were not satisfactory as initially expected in clinical applications, despite the safety and varying degrees of effectiveness in various types of cancer. Improving the efficacy of the DC‑based vaccine is essential for cancer immunotherapy. The present study aimed to investigate methods with which to amplify and enhance the antitumor immune response of a DC‑based tumor vaccine by silencing the expression of indoleamine 2,3‑dioxygenase 2 (IDO2), a tryptophan rate‑limiting metabolic enzyme in DCs.

Targeted Gene Silencing BRAF Synergized Photothermal Effect Inhibits Hepatoma Cell Growth Using New GAL-GNR-siBRAF Nanosystem.

Liver cancer is one of the most common malignancies worldwide. The RAF kinase inhibitors are effective in the treatment of hepatocellular carcinoma (HCC); therefore, inhibition of the BRAF/MEK/ERK pathway has become a new therapeutic strategy for novel HCC therapy. However, targeted specific delivery systems for tumors are still significant obstacle to clinical applications.