CD44-Targeted Nanocarrier for Cancer Therapy

Abstract

Cluster of differentiation 44 (CD44) is a cell surface glycoprotein overexpressed in varieties of solid tumors including pancreatic, breast, ovary, brain, and lung cancers. It is a multi-structural glycoprotein of the cell surface which is majorly involved in cell proliferation, cell-to-cell interaction, cellular migration, inflammation, and generation of immune responses. Numerous studies focus on the development of nanocarriers for active targeting of the CD44 receptor to improve efficacy of targeting chemotherapy and achieve precise chemotherapy by defining the release, uptake, and accumulation of therapeutic agents. The CD44 receptor has a selective binding affinity towards hyaluronic and chondroitin sulfate (CS). Taking this into consideration, this review focused on the role of CD44 in cancer and its therapy using several nanocarriers such as polymeric/non-polymeric nanoparticles, dendrimer, micelles, carbon nanotubes, nanogels, nanoemulsions etc., for targeted delivery of several chemotherapeutic molecules and nucleic acid. This review also illuminates the role of hyaluronic acid (HA) in cancer therapy, interaction of HA with CD44, and various approaches to target CD44-overexpressed neoplastic cells.

Research Progress of Bioinspired Nanostructured Systems for the Treatment of Ocular Disorders

“…For example, CD44 is a cell surface glycoprotein overexpressed highly expressed in ovarian, pancreatic, breast, and lung cancer. The target nanocarrier modified by the variety of different CD44 ligands including the CD44 antibodies, peptide, hyaluronic acid, chitosan, and chondroitin sulfate have been established for the therapy of tumors [ 67 ]. In our previous studies, the CD44 peptide modified polymer micelles [ 68 ] and chitosan functionalized liposomes [ 69 , 70 ] were successfully synthesized and have shown an excellent in vivo and in vitro anti-tumor effect compared with the non-target nanocarriers.…”

Negative regulation of CD44st by miR-138-5p affects the invasive ability of breast cancer cells and patient prognosis after breast cancer surgery

“…CD44 is a transmembrane glycoprotein that is a marker of tumor stem cells and is directly involved in tumor development [8]. It is expressed in connective tissue and cancer cells and is associated with tumor cell proliferation, differentiation, migration, angiogenesis, and chemoresistance [9][10][11]. Although abundant progress has been made regarding the structure and the expression of some CD44 isoforms, including CD44s and CD44v6, the abnormal expression of CD44 isoforms with clinicopathological impacts remains controversial.…”

Green synthesis of hyaluronic acid coated, thiolated chitosan nanoparticles for CD44 targeted delivery and sustained release of Cisplatin in cervical carcinoma

“…A study reported 86% surface expression of CD44 receptor on HeLa, CasKi and INBL cervical cancer cell lines ( Gutiérrez-Hoya et al, 2019 ). CD44/HA has high affinity and upon binding, the receptor/ligand complex is internalized through the caveolin/clathrin mediated endocytosis pathway which leads to higher uptake and retention inside the cell ( Kesharwani et al, 2022 ).…”