Optimum inhibition of MCF-7 breast cancer cells by efficient targeting of the macropinocytosis using optimized paclitaxel-loaded nanoparticles.

Abstract

AIMS:

Breast cancer (BC) is the third leading cause of death among other cancer types. Worldwide, it is the most common harmful disease in women, representing 1/4 of all cancers. Treatment of BC remains an ongoing challenge to most researchers. Understanding how cancer cells differ from normal cells can enhance drug targeting and overall disease progression. Endocytosis is a major physiological process modified in cancer cells and affects the cellular uptake of chemotherapeutic agents. MCF-7 breast cancer cells exhibit constitutive macropinocytic activity in comparison to normal non-macropinocytic MCF-10A breast cells. Therefore, we hypothesized that blocking the macropinocytosis mechanism in MCF-7 cells may inhibit the cancer progression while maintaining the safety of normal cells.

MAIN METHODS:

Using nano-precipitation technique, paclitaxel-PLGA-NPs were successfully prepared in the size range and charge required to opt for macropinocytosis in MCF-7 cells.

KEY FINDINGS:

Uptake and endocytosis inhibitor assays indicated that the developed NPs acquired size and surface charges that efficiently target macropinocytosis of MCF-7 cells. Paclitaxel-loaded PLGA-NPs showed higher efficacy against MCF-7 cells, while providing no toxicity on normal MCF-10A cells. Metabolomics analysis indicated the nutrients deprivation because of occupying the macropinocytosis. However, treatment of fresh MCF-7 cancer cells by metabolites secreted from PLGA-NPs-treated MCF-7 cells showed a potential metastatic activity. Thus, co- administration with an anti-metastatic drug is advised.

SIGNIFICANCE:

Collectively, adjusting the size and surface characteristics of a drug can critically control its cellular uptake, affecting the efficacy of drugs and the microenvironment of cancer cells.

• Authors: Razan B Al-Humaidi, Bahgat Fayed, Sarra B Shakartalla, Jayalakshmi Jagal, Manju N Jayakumar, Zainab M Al Shareef, Suleiman I Sharif, Ayman Noreddin, Mohammad H Semreen, Hany A Omar, Mohamed Haider, Sameh S M Soliman
• Journal: Life sciences (Life Sci) Vol. 305 Pg. 120778 (Sep 15 2022) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 35792181 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• Polylactic Acid-Polyglycolic Acid Copolymer
• Paclitaxel

Topics

• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Female
• Humans
• MCF-7 Cells
• Nanoparticles
• Paclitaxel (pharmacology, therapeutic use)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Tumor Microenvironment