Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

Overview

Journal Antioxidants (Basel)

Date 2020 Jan 16

PMID 31935872

Citations 23

Authors

Silvana Alfei

Barbara Marengo

Cinzia Domenicotti

Affiliations

Soon will be listed here.

Abstract

Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX ) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (-45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells.

Citing Articles

Last Fifteen Years of Nanotechnology Application with Our Contribute.

Alfei S, Zuccari G Nanomaterials (Basel). 2025; 15(4).

PMID: 39997828 PMC: 11858446. DOI: 10.3390/nano15040265.

Ellagic Acid: A Green Multi-Target Weapon That Reduces Oxidative Stress and Inflammation to Prevent and Improve the Condition of Alzheimer's Disease.

Alfei S, Zuccari G Int J Mol Sci. 2025; 26(2).

PMID: 39859559 PMC: 11766176. DOI: 10.3390/ijms26020844.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Alfei S, Zuccari G, Athanassopoulos C, Domenicotti C, Marengo B Int J Mol Sci. 2024; 25(18).

PMID: 39337557 PMC: 11432396. DOI: 10.3390/ijms251810071.

The Remarkable and Selective In Vitro Cytotoxicity of Synthesized Bola-Amphiphilic Nanovesicles on Etoposide-Sensitive and -Resistant Neuroblastoma Cells.

Alfei S, Giannoni P, Signorello M, Torazza C, Zuccari G, Athanassopoulos C Nanomaterials (Basel). 2024; 14(18).

PMID: 39330662 PMC: 11434613. DOI: 10.3390/nano14181505.

Synthesized -Triphenyl Phosphonium-Based Nano Vesicles Have Potent and Selective Antibacterial Effects on Several Clinically Relevant Superbugs.

Alfei S, Zuccari G, Bacchetti F, Torazza C, Milanese M, Siciliano C Nanomaterials (Basel). 2024; 14(16).

PMID: 39195389 PMC: 11357385. DOI: 10.3390/nano14161351.

References

Strife R, Jardine I, Colvin M . Analysis of the anticancer drugs etoposide (VP 16-213) and teniposide (VM 26) by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1981; 224(1):168-74. DOI: 10.1016/s0378-4347(00)80153-x. View

Wang Z, Niu G, Chen X . Polymeric materials for theranostic applications. Pharm Res. 2013; 31(6):1358-76. DOI: 10.1007/s11095-013-1103-7. View

Karlsson J, Ora I, Porn-Ares I, Pahlman S . Arsenic trioxide-induced death of neuroblastoma cells involves activation of Bax and does not require p53. Clin Cancer Res. 2004; 10(9):3179-88. DOI: 10.1158/1078-0432.ccr-03-0309. View

Desai M, Labhasetwar V, Walter E, Levy R, Amidon G . The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res. 1998; 14(11):1568-73. DOI: 10.1023/a:1012126301290. View

Esposito E, Drechsler M, Puglia C, Cortesi R . New Strategies for the Delivery of Some Natural Anti-oxidants with Therapeutic Properties. Mini Rev Med Chem. 2019; 19(13):1030-1039. DOI: 10.2174/1389557519666190228160242. View

Zhou X, Lee K, Cheng J, Wu S, Chen H, Guo X . Antitumor agents. 144. New gamma-lactone ring-modified arylamino etoposide analogs as inhibitors of human DNA topoisomerase II. J Med Chem. 1994; 37(2):287-92. DOI: 10.1021/jm00028a012. View

Li X, Qian Y, Liu T, Hu X, Zhang G, You Y . Amphiphilic multiarm star block copolymer-based multifunctional unimolecular micelles for cancer targeted drug delivery and MR imaging. Biomaterials. 2011; 32(27):6595-605. DOI: 10.1016/j.biomaterials.2011.05.049. View

Hainsworth J, Greco F . Etoposide: twenty years later. Ann Oncol. 1995; 6(4):325-41. DOI: 10.1093/oxfordjournals.annonc.a059180. View

Li Y, Angelova A, Hu F, Garamus V, Peng C, Li N . pH Responsiveness of Hexosomes and Cubosomes for Combined Delivery of Oil and Doxorubicin. Langmuir. 2019; 35(45):14532-14542. DOI: 10.1021/acs.langmuir.9b02257. View

10.

Madaan K, Kumar S, Poonia N, Lather V, Pandita D . Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues. J Pharm Bioallied Sci. 2014; 6(3):139-50. PMC: 4097927. DOI: 10.4103/0975-7406.130965. View

11.

Drewinko B, Barlogie B . Survival and cycle-progression delay of human lymphoma cells in vitro exposed to VP-16-213. Cancer Treat Rep. 1976; 60(9):1295-1306. View

12.

Hourani R, Kakkar A . Advances in the elegance of chemistry in designing dendrimers. Macromol Rapid Commun. 2011; 31(11):947-74. DOI: 10.1002/marc.200900712. View

13.

Shah J, Chen J, Chow D . Preformulation study of etoposide: identification of physicochemical characteristics responsible for the low and erratic oral bioavailability of etoposide. Pharm Res. 1989; 6(5):408-12. DOI: 10.1023/a:1015935532725. View

14.

Rizvi S, Saleh A . Applications of nanoparticle systems in drug delivery technology. Saudi Pharm J. 2018; 26(1):64-70. PMC: 5783816. DOI: 10.1016/j.jsps.2017.10.012. View

15.

Colla R, Izzotti A, Ciucis C, Fenoglio D, Ravera S, Speciale A . Glutathione-mediated antioxidant response and aerobic metabolism: two crucial factors involved in determining the multi-drug resistance of high-risk neuroblastoma. Oncotarget. 2016; 7(43):70715-70737. PMC: 5342585. DOI: 10.18632/oncotarget.12209. View

16.

Van Maanen J, Retel J, de Vries J, Pinedo H . Mechanism of action of antitumor drug etoposide: a review. J Natl Cancer Inst. 1988; 80(19):1526-33. DOI: 10.1093/jnci/80.19.1526. View

17.

Alfei S, Catena S, Ponassi M, Rosano C, Zoppi V, Spallarossa A . Hydrophilic and amphiphilic water-soluble dendrimer prodrugs suitable for parenteral administration of a non-soluble non-nucleoside HIV-1 reverse transcriptase inhibitor thiocarbamate derivative. Eur J Pharm Sci. 2018; 124:153-164. DOI: 10.1016/j.ejps.2018.08.036. View

18.

Hu X, Liu G, Li Y, Wang X, Liu S . Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals. J Am Chem Soc. 2014; 137(1):362-8. DOI: 10.1021/ja5105848. View

19.

Liu D, Angelova A, Liu J, Garamus V, Angelov B, Zhang X . Self-assembly of mitochondria-specific peptide amphiphiles amplifying lung cancer cell death through targeting the VDAC1-hexokinase-II complex. J Mater Chem B. 2019; 7(30):4706-4716. DOI: 10.1039/c9tb00629j. View

20.

Prokop A, Davidson J . Nanovehicular intracellular delivery systems. J Pharm Sci. 2008; 97(9):3518-90. PMC: 3747665. DOI: 10.1002/jps.21270. View