Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Apr 23

PMID 35456622

Authors

Jose M Espejo-Roman

Belen Rubio-Ruiz

Victoria Cano-Cortes

Olga Cruz-Lopez

Saul Gonzalez-Resines

Carmen Domene

Ana Conejo-Garcia

Rosario M Sanchez-Martin

Affiliations

Soon will be listed here.

Abstract

Hyaluronic acid (HA), through its interactions with the cluster of differentiation 44 (CD44), acts as a potent modulator of the tumor microenvironment, creating a wide range of extracellular stimuli for tumor growth, angiogenesis, invasion, and metastasis. An innovative antitumor treatment strategy based on the development of a nanodevice for selective release of an inhibitor of the HA-CD44 interaction is presented. Computational analysis was performed to evaluate the interaction of the designed tetrahydroisoquinoline-ketone derivative () with CD44 binding site. Cell viability, efficiency, and selectivity of drug release under acidic conditions together with CD44 binding capacity, effect on cell migration, and apoptotic activity were successfully evaluated. Remarkably, the conjugation of this CD44 inhibitor to the nanodevice generated a reduction of the dosis required to achieve a significant therapeutic effect.

Citing Articles

CD44 and its implication in neoplastic diseases.

Xu Y, Bai Z, Lan T, Fu C, Cheng P MedComm (2020). 2024; 5(6):e554.

PMID: 38783892 PMC: 11112461. DOI: 10.1002/mco2.554.

Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.

MacLean M, Walker O, Arun R, Fernando W, Marcato P Int J Mol Sci. 2024; 25(7).

PMID: 38612911 PMC: 11012648. DOI: 10.3390/ijms25074102.

From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment.

Astrain-Redin N, Sanmartin C, Sharma A, Plano D J Med Chem. 2023; 66(6):3703-3731.

PMID: 36858050 PMC: 10041541. DOI: 10.1021/acs.jmedchem.2c01406.

An Overview of Antitumour Activity of Polysaccharides.

Jin H, Li M, Tian F, Yu F, Zhao W Molecules. 2022; 27(22).

PMID: 36432183 PMC: 9692906. DOI: 10.3390/molecules27228083.

References

Fallacara A, Baldini E, Manfredini S, Vertuani S . Hyaluronic Acid in the Third Millennium. Polymers (Basel). 2019; 10(7). PMC: 6403654. DOI: 10.3390/polym10070701. View

Ali H, Al-Yatama M, Abu-Farha M, Behbehani K, Madhoun A . Multi-lineage differentiation of human umbilical cord Wharton's Jelly Mesenchymal Stromal Cells mediates changes in the expression profile of stemness markers. PLoS One. 2015; 10(4):e0122465. PMC: 4388513. DOI: 10.1371/journal.pone.0122465. View

Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J . CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem. 2009; 31(4):671-90. PMC: 2888302. DOI: 10.1002/jcc.21367. View

Liu L, Finzel B . Fragment-based identification of an inducible binding site on cell surface receptor CD44 for the design of protein-carbohydrate interaction inhibitors. J Med Chem. 2014; 57(6):2714-25. DOI: 10.1021/jm5000276. View

Cano-Cortes M, Navarro-Marchal S, Ruiz-Blas M, Diaz-Mochon J, Marchal J, Sanchez-Martin R . A versatile theranostic nanodevice based on an orthogonal bioconjugation strategy for efficient targeted treatment and monitoring of triple negative breast cancer. Nanomedicine. 2019; 24:102120. DOI: 10.1016/j.nano.2019.102120. View

Jo S, Lim J, Klauda J, Im W . CHARMM-GUI Membrane Builder for mixed bilayers and its application to yeast membranes. Biophys J. 2009; 97(1):50-8. PMC: 2711372. DOI: 10.1016/j.bpj.2009.04.013. View

Chiesa E, Greco A, Riva F, Dorati R, Conti B, Modena T . Hyaluronic Acid-Based Nanoparticles for Protein Delivery: Systematic Examination of Microfluidic Production Conditions. Pharmaceutics. 2021; 13(10). PMC: 8539066. DOI: 10.3390/pharmaceutics13101565. View

Fraser J, Laurent T, Laurent U . Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997; 242(1):27-33. DOI: 10.1046/j.1365-2796.1997.00170.x. View

Zhong Z, Tan W, Tian K, Yu H, Qiang W, Wang Y . Combined effects of furanodiene and doxorubicin on the migration and invasion of MDA-MB-231 breast cancer cells in vitro. Oncol Rep. 2017; 37(4):2016-2024. DOI: 10.3892/or.2017.5435. View

10.

Tsujimoto Y, Shimizu S . Role of the mitochondrial membrane permeability transition in cell death. Apoptosis. 2006; 12(5):835-40. DOI: 10.1007/s10495-006-0525-7. View

11.

Kim S, Lee J, Jo S, Brooks 3rd C, Lee H, Im W . CHARMM-GUI ligand reader and modeler for CHARMM force field generation of small molecules. J Comput Chem. 2017; 38(21):1879-1886. PMC: 5488718. DOI: 10.1002/jcc.24829. View

12.

Pietrovito L, Cano-Cortes V, Gamberi T, Magherini F, Bianchi L, Bini L . Cellular response to empty and palladium-conjugated amino-polystyrene nanospheres uptake: a proteomic study. Proteomics. 2014; 15(1):34-43. DOI: 10.1002/pmic.201300423. View

13.

Unciti-Broceta J, Cano-Cortes V, Altea-Manzano P, Pernagallo S, Diaz-Mochon J, Sanchez-Martin R . Number of Nanoparticles per Cell through a Spectrophotometric Method - A key parameter to Assess Nanoparticle-based Cellular Assays. Sci Rep. 2015; 5:10091. PMC: 4432369. DOI: 10.1038/srep10091. View

14.

Cano-Cortes M, Laz-Ruiz J, Diaz-Mochon J, Sanchez-Martin R . Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release. Polymers (Basel). 2020; 12(6). PMC: 7361709. DOI: 10.3390/polym12061265. View

15.

Sheridan C, Kishimoto H, Fuchs R, Mehrotra S, Bhat-Nakshatri P, Turner C . CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006; 8(5):R59. PMC: 1779499. DOI: 10.1186/bcr1610. View

16.

Altea-Manzano P, Unciti-Broceta J, Cano-Cortes V, Ruiz-Blas M, Valero-Grinan T, Diaz-Mochon J . Tracking cell proliferation using a nanotechnology-based approach. Nanomedicine (Lond). 2017; 12(13):1591-1605. DOI: 10.2217/nnm-2017-0118. View

17.

Valero T, Delgado-Gonzalez A, Unciti-Broceta J, Cano-Cortes V, Perez-Lopez A, Unciti-Broceta A . Drug "Clicking" on Cell-Penetrating Fluorescent Nanoparticles for In Cellulo Chemical Proteomics. Bioconjug Chem. 2018; 29(9):3154-3160. DOI: 10.1021/acs.bioconjchem.8b00481. View

18.

Navarro-Marchal S, Grinan-Lison C, Entrena J, Ruiz-Alcala G, Tristan-Manzano M, Martin F . Anti-CD44-Conjugated Olive Oil Liquid Nanocapsules for Targeting Pancreatic Cancer Stem Cells. Biomacromolecules. 2021; 22(4):1374-1388. DOI: 10.1021/acs.biomac.0c01546. View

19.

Karousou E, Misra S, Ghatak S, Dobra K, Gotte M, Vigetti D . Roles and targeting of the HAS/hyaluronan/CD44 molecular system in cancer. Matrix Biol. 2016; 59:3-22. DOI: 10.1016/j.matbio.2016.10.001. View

20.

Olsson E, Honeth G, Bendahl P, Saal L, Gruvberger-Saal S, Ringner M . CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers. BMC Cancer. 2011; 11:418. PMC: 3196967. DOI: 10.1186/1471-2407-11-418. View