Staff member

Colorectal cancer (CRC) ranks among the most common cancers and is the second leading cause of cancer-related deaths. The high mortality associated with CRC is attributed mainly to difficulties in early detection and lack of effective targeted therapies. The Transferrin receptor 1 (TfR1) is particularly attractive as a therapy target given its notable overexpression in tumor cells, particularly in CRC. This study explored the potential of a polymeric nanoparticle (PSomes)-based drug delivery system targeting TfR1 to improve the precision and efficacy of CRC treatment. For this study, we used two human CRC cell lines (HT-29, and HCT116), a healthy human intestinal epithelial cell line (hIECs), and a murine CRC cell line (MC38). We engineered PSomes composed of poly (ethylene glycol) (PEG) and poly (lactic acid) (PLA), functionalized with the T7 peptide to enhance their specificity for TfR1-expressing cells. Targeting efficiency of these PSomes was assessed across all cell lines by evaluating the cellular uptake using flow cytometry. Upon establishing the optimal formulation for these NPs for TfR1-targeting, we encapsulated doxorubicin (DOX) to assess their therapeutic potential. Both in vitro and in vivo experiments demonstrated that DOX loaded TfR1-targeted PSomes delivered DOX to CRC cells, leading to efficient induction of CRC cell death, reducing tumor growth and improving survival rates, compared to the control groups. These results highlight the promise of TfR1-targeted PSomes as a precise strategy for CRC therapy, offering enhanced treatment efficacy while reducing systemic toxicity. This novel approach could lead to more targeted and less harmful cancer treatments.

JTD Keywords: Colorectal cancer, Delivery, Doxorubicin, Nanoparticles, Polymersomes, Size, T7, Targeted delivery, Transferrin receptor

The diverse roles of the low-density lipoprotein receptor family (LDLR) have been associated with many processes critical to maintaining central nervous system (CNS) health and contributing to neurological diseases or cancer. In this review, we provide a comprehensive understanding of the LDLR's involvement in common brain tumors, specifically high-grade gliomas, emphasizing the receptors' critical role in the pathophysiology and progression of these tumors due to LDLR's high expression. We delve into LDLR's role in regulating cellular uptake and transport through the brain barrier. Additionally, we highlight LDLR's role in activating several signaling pathways related to tumor proliferation, migration, and invasion, engaging readers with an in-depth understanding of the molecular mechanisms at play. By synthesizing current research findings, this review underscores the significance of LDLR during tumorigenesis and explores its potential as a therapeutic target for high-grade gliomas. The collective insights presented here contribute to a deeper appreciation of LDLR's multifaceted roles and implications for physiological and pathological states, opening new avenues for tumor treatment. The role of LDLR family receptors in mediating the transport of LDL across the blood-brain barrier (BBB), facilitating processes such as survival, proliferation, and invasion in high-grade gliomas. Nanoparticles targeting LDLR can be used for drug delivery, potentially inducing cell death and reducing tumor proliferation and survival in high-grade glioma cells. image

JTD Keywords: Animals, Blood-brain-barrier, Brain neoplasms, Cancer, Delivery, Doxorubicin, Expression, Glioblastomas, Glioma, Humans, Low-density lipoprotein receptors, Low‐density lipoprotein receptors, Migratio, Nanoparticles, Neoplasm grading, Proliferation, Receptors, ldl, Signal transduction, Targeted therapie, Targeted therapies, Targeting therapy, Tumor microenvironment