Smart Lipid-Polysaccharide Nanoparticles for Targeted Delivery of Doxorubicin to Breast Cancer Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Feb 26

PMID 35216501

Authors

Manuela Curcio

Matteo Brindisi

Giuseppe Cirillo

Luca Frattaruolo

Antonella Leggio

Vittoria Rago

Fiore Pasquale Nicoletta

Anna Rita Cappello

Francesca Iemma

Affiliations

Soon will be listed here.

Abstract

In this study, actively-targeted (CD44-receptors) and dual stimuli (pH/redox)-responsive lipid-polymer nanoparticles were proposed as a delivery vehicle of doxorubicin hydrochloride in triple negative breast cancer cell lines. A phosphatidylcholine lipid film was hydrated with a solution of oxidized hyaluronic acid and doxorubicin, chosen as model drug, followed by a crosslinking reaction with cystamine hydrochloride. The obtained spherical nanoparticles (mean diameter of 30 nm) were found to be efficiently internalized in cancer cells by a receptor-mediated endocytosis process, and to modulate the drug release depending on the pH and redox potential of the surrounding medium. In vitro cytotoxicity assays demonstrated the safety and efficacy of the nanoparticles in enhancing the cytotoxic effect of the free anticancer drug, with the IC values being reduced by two and three times in MDA-MB-468 and MDA-MB-231, respectively. The combination of self-assembled phospholipid molecules with a polysaccharide counterpart acting as receptor ligand, and stimuli-responsive chemical moieties, was carried out on smart multifunctional nanoparticles able to actively target breast cancer cells and improve the in vitro anticancer activity of doxorubicin.

Citing Articles

Plant polysaccharide-capped nanoparticles: A sustainable approach to modulate gut microbiota and advance functional food applications.

Bamigbade G, Abdin M, Subhash A, Arachchi M, Ullah N, Gan R Compr Rev Food Sci Food Saf. 2025; 24(2):e70156.

PMID: 40052474 PMC: 11887029. DOI: 10.1111/1541-4337.70156.

Exploiting L. (Licorice) Flavanones: Licoflavanone's Impact on Breast Cancer Cell Bioenergetics.

Frattaruolo L, Lauria G, Aiello F, Carullo G, Curcio R, Fiorillo M Int J Mol Sci. 2024; 25(14).

PMID: 39063149 PMC: 11276871. DOI: 10.3390/ijms25147907.

Uncovering the Emerging Prospects of Lipid-based Nanoparticulate Vehicles in Lung Cancer Management: A Recent Perspective.

Gupta D, Suares D Pharm Nanotechnol. 2024; 13(1):155-170.

PMID: 38468532 DOI: 10.2174/0122117385286781240228060152.

Advances in Doxorubicin-based nano-drug delivery system in triple negative breast cancer.

Zeng W, Luo Y, Gan D, Zhang Y, Deng H, Liu G Front Bioeng Biotechnol. 2023; 11:1271420.

PMID: 38047286 PMC: 10693343. DOI: 10.3389/fbioe.2023.1271420.

Facile one-pot hydrothermal synthesis of a zinc oxide/curcumin nanocomposite with enhanced toxic activity against breast cancer cells.

Madeo L, Schirmer C, Cirillo G, Froeschke S, Hantusch M, Curcio M RSC Adv. 2023; 13(39):27180-27189.

PMID: 37701282 PMC: 10493854. DOI: 10.1039/d3ra05176e.

References

Schafer F, Buettner G . Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001; 30(11):1191-212. DOI: 10.1016/s0891-5849(01)00480-4. View

Green P, Leeuwenburgh C . Mitochondrial dysfunction is an early indicator of doxorubicin-induced apoptosis. Biochim Biophys Acta. 2002; 1588(1):94-101. DOI: 10.1016/s0925-4439(02)00144-8. View

Pandit A, Mazumdar N, Ahmad S . Periodate oxidized hyaluronic acid-based hydrogel scaffolds for tissue engineering applications. Int J Biol Macromol. 2019; 137:853-869. DOI: 10.1016/j.ijbiomac.2019.07.014. View

Fang J, Nakamura H, Maeda H . The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev. 2010; 63(3):136-51. DOI: 10.1016/j.addr.2010.04.009. View

Collins A, Dusinska M, Franklin M, Somorovska M, Petrovska H, Duthie S . Comet assay in human biomonitoring studies: reliability, validation, and applications. Environ Mol Mutagen. 1997; 30(2):139-46. DOI: 10.1002/(sici)1098-2280(1997)30:2<139::aid-em6>3.0.co;2-i. View

Joo H, Park J, Sutthiwanjampa C, Kim H, Bae T, Kim W . Surface Coating with Hyaluronic Acid-Gelatin-Crosslinked Hydrogel on Gelatin-Conjugated Poly(dimethylsiloxane) for Implantable Medical Device-Induced Fibrosis. Pharmaceutics. 2021; 13(2). PMC: 7922955. DOI: 10.3390/pharmaceutics13020269. View

Ewurum A, Alur A, Glenn M, Schnepf A, Borchman D . Hyaluronic acid-lipid binding. BMC Chem. 2021; 15(1):36. PMC: 8161914. DOI: 10.1186/s13065-021-00763-0. View

Kim H, Lee K, Kim S, Kwon Y, Chun Y, Choi H . Comparative metabolic and lipidomic profiling of human breast cancer cells with different metastatic potentials. Oncotarget. 2016; 7(41):67111-67128. PMC: 5341861. DOI: 10.18632/oncotarget.11560. View

Haley B, Frenkel E . Nanoparticles for drug delivery in cancer treatment. Urol Oncol. 2008; 26(1):57-64. DOI: 10.1016/j.urolonc.2007.03.015. View

10.

De Leo V, Milano F, Agostiano A, Catucci L . Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles. Polymers (Basel). 2021; 13(7). PMC: 8037206. DOI: 10.3390/polym13071027. View

11.

Curcio M, Cirillo G, Paoli A, Naimo G, Mauro L, Amantea D . Self-assembling Dextran prodrug for redox- and pH-responsive co-delivery of therapeutics in cancer cells. Colloids Surf B Biointerfaces. 2019; 185:110537. DOI: 10.1016/j.colsurfb.2019.110537. View

12.

Iacopetta D, Lappano R, Cappello A, Madeo M, De Francesco E, Santoro A . SLC37A1 gene expression is up-regulated by epidermal growth factor in breast cancer cells. Breast Cancer Res Treat. 2009; 122(3):755-64. DOI: 10.1007/s10549-009-0620-x. View

13.

Cheng S, Tseng Y, Wu S, Tsai S, Tsai L . Whey Protein Concentrate Renders MDA-MB-231 Cells Sensitive to Rapamycin by Altering Cellular Redox State and Activating GSK3β/mTOR Signaling. Sci Rep. 2017; 7(1):15976. PMC: 5698404. DOI: 10.1038/s41598-017-14159-5. View

14.

Zhao Q, Liu J, Zhu W, Sun C, Di D, Zhang Y . Dual-stimuli responsive hyaluronic acid-conjugated mesoporous silica for targeted delivery to CD44-overexpressing cancer cells. Acta Biomater. 2015; 23:147-156. DOI: 10.1016/j.actbio.2015.05.010. View

15.

Park H, Lee S, Oh J, Lee S, Jeong Y, Lee H . Smart Nanoparticles Based on Hyaluronic Acid for Redox-Responsive and CD44 Receptor-Mediated Targeting of Tumor. Nanoscale Res Lett. 2015; 10(1):981. PMC: 4499038. DOI: 10.1186/s11671-015-0981-5. View

16.

Martin H, Smith L, Tomlinson D . Multidrug-resistant breast cancer: current perspectives. Breast Cancer (Dove Med Press). 2014; 6:1-13. PMC: 3929252. DOI: 10.2147/BCTT.S37638. View

17.

Rao N, Rho J, Um W, Ek P, Nguyen V, Oh B . Hyaluronic Acid Nanoparticles as Nanomedicine for Treatment of Inflammatory Diseases. Pharmaceutics. 2020; 12(10). PMC: 7600604. DOI: 10.3390/pharmaceutics12100931. View

18.

Sercombe L, Veerati T, Moheimani F, Wu S, Sood A, Hua S . Advances and Challenges of Liposome Assisted Drug Delivery. Front Pharmacol. 2015; 6:286. PMC: 4664963. DOI: 10.3389/fphar.2015.00286. View

19.

Brindisi M, Frattaruolo L, Mancuso R, Palumbo Piccionello A, Ziccarelli I, Catto M . Anticancer potential of novel α,β-unsaturated γ-lactam derivatives targeting the PI3K/AKT signaling pathway. Biochem Pharmacol. 2021; 190:114659. DOI: 10.1016/j.bcp.2021.114659. View

20.

Hayward S, Wilson C, Kidambi S . Hyaluronic acid-conjugated liposome nanoparticles for targeted delivery to CD44 overexpressing glioblastoma cells. Oncotarget. 2016; 7(23):34158-71. PMC: 5085145. DOI: 10.18632/oncotarget.8926. View