α1-Acid Glycoprotein-Decorated Hyaluronic Acid Nanoparticles for Suppressing Metastasis and Overcoming Drug Resistance Breast Cancer

Haneen Omar; Roa' Fardous; Yasser M Alhindi; Alhassan H Aodah; Mram Alyami; Mohammed S Alsuabeyl; Waleed M Alghamdi; Ali H Alhasan; Abdulaziz Almalik

doi:10.3390/biomedicines10020414

α₁-Acid Glycoprotein-Decorated Hyaluronic Acid Nanoparticles for Suppressing Metastasis and Overcoming Drug Resistance Breast Cancer

Biomedicines. 2022 Feb 9;10(2):414. doi: 10.3390/biomedicines10020414.

Authors

Haneen Omar^{1

2}, Roa' Fardous^{1

2}, Yasser M Alhindi^{1

2}, Alhassan H Aodah^{1

3}, Mram Alyami⁴, Mohammed S Alsuabeyl¹, Waleed M Alghamdi¹, Ali H Alhasan^{1

2

5

6}, Abdulaziz Almalik^{1

2}

Affiliations

¹ National Center for Pharmaceutical Technology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11564, Saudi Arabia.
² KACST-BWH/Harvard Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh 11533, Saudi Arabia.
³ Pharmaceutical Analysis Lab at King Abdulaziz City for Science and Technology (PALab), Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11533, Saudi Arabia.
⁴ Smart Hybrid Materials (SHMs) Laboratory, Advanced Membranes and Porous Materials Center, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia.
⁵ National Center for Biotechnology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh 11533, Saudi Arabia.
⁶ College of Science and General Studies, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia.

Abstract

Robust inflammation-suppressing nanoparticles based on α₁-acid glycoprotein (AGP)-conjugated hyaluronic acid nanoparticles (AGP-HA NPs) were designed to regulate breast cancer cells' sensitivity to chemotherapy and to suppress tumor metastasis. The successful conjugation between AGP and HA NPs was confirmed using FTIR, zeta potential, and UV-vis spectroscopy. In vitro studies on MCF-7 cells indicated the remarkable ability of AGP-HA NPs in suppressing migratory tumor ability by 79% after 24 h. Moreover, the efficacy study showed the high capability of AGP-HA NPs in modulating MDA-MB-231 cells and restoring cell sensitivity to the chemotherapeutic drug doxorubicin (DOX). Furthermore, the finding obtained by flow cytometry and confocal spectroscopy demonstrated that AGP-HA NPs enhanced DOX uptake/retention and aided it to reach cell nucleus within 4 h of incubation. Therefore, AGP-HA NPs represent a viable and effective treatment option to strengthen the anticancer effects of chemotherapeutic agents and potentially improve patients' survival rates.

Keywords: breast cancer cells; hyaluronic acid (HA) nanoparticles; immune-suppressing nanoparticles; multidrug resistance (MDR); tumor metastasis; α1-acid glycoprotein (AGP).