Folate-receptor mediated pH/reduction-responsive biomimetic nanoparticles for dually activated multi-stage anticancer drug delivery.

Abstract

How to overcome the cell membrane barriers and achieve release payloads efficiently in the cytoplasm have been major challenges for anticancer drug delivery and therapeutic effects with nanosystems. In this study, bovine serum albumin (BSA) was modified with folate acid and histamine, which was then used as the nanocarrier for the antitumor agent doxorubicin (DOX). The DOX-loaded nanoparticles (DOX/FBH-NPs) were prepared via a crosslinking method, and the release of DOX from these nanoparticles (NPs) exhibited pH/reduction-responsive behaviors in vitro. These NPs interacted with the folate receptor overexpressed on the cell membrane of 4 T1 cells and achieved enhanced endocytosis. Afterwards, these NPs exhibited pH-responsiveness within endo-lysosomes and escaped from endosomes due to the "proton sponge" effect, and then completed release of DOX was triggered by high concentration of glutathione (GSH) in cytoplasm. Thus, DOX/FBH-NPs exhibited excellent cytotoxicity against 4 T1 cells in vitro. Benefited from the enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis, these NPs gained satisfied tumor-targeting effects in vivo and efficient delivery of DOX to tumor tissues. As a result, these NPs exhibited enhanced antitumor effects and reduced side effects in vivo. In conclusion, these BSA-based NPs modified with both folate acid and histamine showed enhanced tumor-targeting effects in vivo with good biocompatibility and intracellular pH/reduction-responsive behaviors, providing a promising strategy for the efficient delivery of antitumor agents.

• Authors: Dandan Wang, Weiliang Chen, Hui Li, Gui Huang, Yejuan Zhou, Yu Wang, Wenjun Wan, Bengang You, Yang Liu, Xuenong Zhang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 585 Pg. 119456 (Jul 30 2020) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 32492507 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Serum Albumin, Bovine
• Doxorubicin
• Histamine
• Folic Acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Cell Survival
• Chemistry, Pharmaceutical
• Doxorubicin (administration & dosage, pharmacokinetics, pharmacology)
• Drug Carriers (administration & dosage, pharmacology)
• Drug Delivery Systems (methods)
• Drug Liberation
• Endocytosis (drug effects)
• Folic Acid (chemistry)
• Histamine
• Hydrogen-Ion Concentration
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Serum Albumin, Bovine (chemistry)