Wenjing Yu

YKL-40 is a glycoprotein that has been extensively studied due to its elevated expression in numerous solid tumors, and its expression is altered in melanoma, where its levels in tumor tissues are notably lower compared with those in normal skin tissues. Patients with melanoma exhibiting high YKL-40 expression have improved survival rates, suggesting a potential tumor-suppressive function of YKL-40 in melanoma. The present investigation into the ectopic expression of YKL-40 in human (A375) and murine (B16F10) melanoma cell lines demonstrated a consequential decrease in cell proliferation, migration and invasion. Furthermore, YKL-40 overexpression was associated with suppressed tumor growth in a subcutaneous melanoma mouse model and diminished tumor cell metastasis in a pulmonary metastasis model. RNA-sequencing analysis revealed that YKL-40 overexpression led to the upregulation of immune cell infiltration-related signaling pathways, including cytokine receptor interactions, natural killer cell-mediated cytotoxicity, and T and B lymphocyte receptor signaling. These findings highlight the potential of YKL-40 as a regulator of tumor-immune interactions in melanoma, highlighting its prospective utility in immunotherapy-based treatment strategies for melanoma.

Globally, non‑small cell lung cancer (NSCLC) is a significant threat to human health, and constitutes >80% of lung cancer cases. Cisplatin (CDDP), a commonly used drug in clinical treatment, has been the focus of research aiming to mitigate its potent toxicity through encapsulation within liposomes. However, challenges, such as a reduced drug loading efficiency and nonspecific release, have emerged as obstacles. The present study aimed to improve the encapsulation efficiency of CDDP within liposomes by pre‑preparation of CDDP and modifying the liposome surface through the incorporation of peanut agglutinin (PNA) as a ligand [CDDP‑loaded PNA‑modified liposomes (CDDP‑PNA‑Lip)]. This strategy was designed to enhance the delivery of CDDP to tumour tissues, thereby reducing associated side effects. The effect of CDDP‑PNA‑Lip on the proliferation and migration of NSCLC cell lines with high MUC1 expression was elucidated through in vitro studies. Additionally, the capacity of PNA modification to augment the targeted anti‑tumour efficacy of liposomes was assessed through xenograft tumour experiments. The results indicated that in an in vitro uptake assay Rhodamine B (RhB)‑loaded PNA‑modified liposomes were taken up by cells with ~50% higher efficiency compared with free RhB. In addition, CDDP‑PNA‑Lip resulted in a 2.65‑fold enhancement of tumour suppression in vivo compared with free CDDP. These findings suggested that the encapsulation of CDDP within ligand‑modified liposomes may significantly improve its tumour‑targeting capabilities, providing valuable insights for clinical drug development.

Mucin 1 belongs to the membrane-binding mucoprotein subfamily, which is normally a highly O-glycosylated polymer protein that is mainly expressed in epithelial cells and some hematopoietic cells. Mucin 1 was overexpressed in many cancer tissues compared to normal tissue with a lower degree of glycosylation. Mucin 1 is weakly O-glycosylated in tumor cells, the core site is exposed, and it is widely distributed on the surface of tumor cells, making it an important tumor marker. Mucin 1 has a wide range of applications in tumor diagnosis, tumor drug targeted delivery, and immunodeficiency therapy. Animal studies and clinical studies suggest that mucin 1 can be used as a target in tumor-targeted therapy. This review covers our current summary of the structure and function of mucin 1, reveals its expression in human tumors, focuses on mucin 1-based targeted therapy regimens, and summarizes the research progress of mucin 1 in targeted tumor therapy.

Tumor-associated antigen mucin 1 (MUC1) is highly expressed in colorectal cancer and is positively correlated with advanced stage at diagnosis and poor patient outcomes. The combination of irinotecan and capecitabine is standard chemotherapy for metastatic colorectal cancer and is known as XELIRI or CAPIRI, which significantly prolongs the progression-free survival and overall survival of colorectal cancer patients compared to a single drug alone. We previously reported that peanut agglutinin (PNA)-conjugated liposomes showed enhanced drug delivery efficiency to MUC1-positive liver cancer cells. In this study, we prepared irinotecan hydrochloride (IRI) and capecitabine (CAP)-coloaded liposomes modified by peanut agglutinin (IRI/CAP-PNA-Lips) to target MUC1-positive colorectal cancer. The results showed that IRI/CAP-PNA-Lips showed an enhanced ability to target MUC1-positive colorectal cancer cells compared to unmodified liposomes. Treatment with IRI/CAP-PNA-Lips also increased the proportion of apoptotic cells and inhibited the proliferation of colorectal cancer cells. The targeting specificity for tumor cells and the antitumor effects of PNA-modified liposomes were significantly increased in tumor-bearing mice with no severe cytotoxicity to normal tissues. These results suggest that PNA-modified liposomes could provide a new delivery strategy for the synergistic treatment of colorectal cancer with clinical chemotherapeutic agents.

The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid–glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA–GA/HA–His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via ¹H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA–GA/HA–His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA–GA/HA–His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA–GA/HA–His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.