Chemical Biology and Drug Design
Chemical Biology and Drug Design
5 years ago

Design and fabrication of dual-targeted delivery system based on gemcitabine conjugated human serum albumin nanoparticles

Design and fabrication of dual-targeted delivery system based on gemcitabine conjugated human serum albumin nanoparticles
Farnaz Sadat Mirzazadeh Tekie, Mohsen amini, Parisa Norouzi, Fatemeh Atyabi, Fatemeh Mottaghitalab, Zahra Hadavand Mirzaie, Rassoul Dinarvand
Dual-targeted drug delivery system has established their reputation as potent vehicles for cancer chemotherapies. Herein, gemcitabine (Gem) was conjugated to human serum albumin (HSA) via dithiodipropionic anhydride (DTDPA) to fabricate Gem-HSA nanoparticles. It was hypothesized that this system can enhance the low stability of Gem and can improve its intracellular delivery. Furthermore, folate was applied as targeting agent on HSA nanoparticles for increasing the tumor selectivity of Gem. In order to evaluate the structural properties of synthesized products, 1H NMR and FT-IR were performed. Moreover, HPLC was implemented for confirming the conjugation between HSA and Gem. Nanoparticles have shown spherical shape with negative charge. The release rate of Gem was dependent to the concentration of glutathione and pH. Folate-targeted HSA nanoparticles have shown higher cytotoxicity, cellular uptake and apoptosis induction on folate receptor overexpressing MDA-MB-231 cells in comparison to non-targeted nanoparticles. Finally, it is considered that the developed dual-targeted nanoparticles would be potent in improving the stability and efficacy of intracellular delivery of Gem and its selective delivery to cancer cells. This article is protected by copyright. All rights reserved. In the present study, we prepared folate targeted Gem-HSA nanoparticles. Dithiodipropionic anhydride disulfide linker was used to conjugate Gem with HSA. Nanoparticles had spherical shape and negative charge. Release rate of Gem from nanoparticles was accelerated under reductive and acidic pH. Folate targeting of nanoparticles improved the cytotoxicity, cellular uptake and apoptosis induction of nanoparticles. The dual- targeted nanoparticles enhanced the stability and efficacy of Gem by intracellular release and selective delivery to cancer cells.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/cbdd.13044

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.