bims-nucpor 2024-06-16 papers

Issue of 2024‒06‒16
two papers selected by
Sara Mingu, Johannes Gutenberg University

J Adv Res. 2024 Jun 12. pii: S2090-1232(24)00245-5. [Epub ahead of print]

Targeting colorectal cancer at the level of nuclear pore complex.

Muhammad Mahtab Aslam Khan Khakwani, Xin-Ying Ji, Saadullah Khattak, Ying-Chuan Sun, Kunhou Yao, Lei Zhang.

BACKGROUND: Nuclear pore complexes (NPCs) are the architectures entrenched in nuclear envelop of a cell that regulate the nucleo-cytoplasmic transportation of materials such as proteins and RNAs for proper functioning of a cell. The appropriate localization of proteins and RNAs within the cell is essential for its normal functionality. For such a complex transportation of materials across the NPC, around 60 proteins are involved comprising nucleoporins, karyopherins and RAN system proteins that play a vital role in NPC's structure formation, cargo translocation across NPC, and cargoes' rapid directed transportation respectively. In various cancers, the structure and function of NPC is often exaggerated, following altered expressions of its nucleoporins and karyopherins, affecting other proteins of associated signaling pathways. Some inhibitors of karyopherins at present have potential to regulate the altered level/expression of these karyopherin molecules.AIM OF REVIEW: This review summarizes the data from 1990 to 2023, mainly focusing on recent studies that illustrate the structure and function of NPC, the relationship and mechanisms of nucleoporins and karyopherins with colorectal cancer, as well as therapeutic values, in order to understand the pathology and underlying basis of colorectal cancer associated with NPC. This is the first review to our knowledge elucidating the detailed updated studies targeting colorectal cancer at NPC. The review also aims to target certain karyopherins, nups and their possible inhibitors and activators molecules as a therapeutic strategy.
KEY SCIENTIFIC CONCEPTS OF REVIEW: NPC structure provides understanding, how nucleoporins and karyopherins as key molecules are responsible for appropriate nucleocytoplasmic transportation. Many studies provide evidences describing the role of disrupted nucleoporins and karyopherins not only in CRC but also in other non-hematological and hematological malignancies. At present, some inhibitors of karyopherins have therapeutic potential for CRC, however development of more potent inhibitors may provide more effective therapeutic strategies for CRC in near future.

Keywords: Colorectal cancer (CRC); Karyopherins; Nuclear pore complex (NPC); Nuclear transporters; Nucleocytoplasmic transport; Nucleoporins

DOI: https://doi.org/10.1016/j.jare.2024.06.009

Adv Drug Deliv Rev. 2024 Jun 09. pii: S0169-409X(24)00176-5. [Epub ahead of print]211 115354

Nanoassemblies designed for efficient nuclear targeting.

Michal Skowicki, Shabnam Tarvirdipour, Manuel Kraus, Cora-Ann Schoenenberger, Cornelia G Palivan.

One of the key aspects of coping efficiently with complex pathological conditions is delivering the desired therapeutic compounds with precision in both space and time. Therefore, the focus on nuclear-targeted delivery systems has emerged as a promising strategy with high potential, particularly in gene therapy and cancer treatment. Here, we explore the design of supramolecular nanoassemblies as vehicles to deliver specific compounds to the nucleus, with the special focus on polymer and peptide-based carriers that expose nuclear localization signals. Such nanoassemblies aim at maximizing the concentration of genetic and therapeutic agents within the nucleus, thereby optimizing treatment outcomes while minimizing off-target effects. A complex scenario of conditions, including cellular uptake, endosomal escape, and nuclear translocation, requires fine tuning of the nanocarriers' properties. First, we introduce the principles of nuclear import and the role of nuclear pore complexes that reveal strategies for targeting nanosystems to the nucleus. Then, we provide an overview of cargoes that rely on nuclear localization for optimal activity as their integrity and accumulation are crucial parameters to consider when designing a suitable delivery system. Considering that they are in their early stages of research, we present various cargo-loaded peptide- and polymer nanoassemblies that promote nuclear targeting, emphasizing their potential to enhance therapeutic response. Finally, we briefly discuss further advancements for more precise and effective nuclear delivery.

Keywords: Micelle; Nanoassemblies; Nuclear localization signal; Nuclear targeting; Peptidic; Peptiplex; Polymeric; Polyplex

DOI: https://doi.org/10.1016/j.addr.2024.115354