Codelivery of BV6 and anti-IL6 siRNA by hyaluronate-conjugated PEG-chitosan-lactate nanoparticles inhibits tumor progression.

Abstract

AIMS:

Increased expression of inhibitor of apoptosis (IAP) genes has been associated with progressive cancer and chemoresistance. Accordingly, blockade of IAPs by BV6 has resulted in ameliorative outcomes. Interleukin (IL)-6 is another important mediator involved in the growth and survival of tumor cells. Therefore, we hypothesized that simultaneous inhibition of IAPs and IL-6 could be a new promising anti-tumor treatment strategy.

MATERIALS AND METHODS:

In this study, we generated and characterized hyaluronate-PEG-Chitosan-Lactate (H-PCL) nanoparticles (NPs) to simultaneously deliver IL6-specific siRNA and BV6 to 4T1 (breast cancer) and CT26 (colon cancer) cells, and investigate the anti-tumor properties of this combination therapy both in vitro and in vivo.

KEY FINDINGS:

H-PCL NPs exhibited good physicochemical properties leading to efficient transfection of cancer cells and suppression of target molecules. Moreover, combination therapy synergistically increased apoptosis, as well as decreased cell migration, proliferation, colony formation, and angiogenesis in both 4T1 and CT26 cell lines and suppressed cancer progression in tumor-bearing mice that was associated with enhanced survival time.

SIGNIFICANCE:

These findings imply the effectiveness of cancer combination therapy by using H-PCL NPs loaded with anti-IL-6 siRNA and BV6.

• Authors: Sevda Salimifard, Fariba Karoon Kiani, Farzaneh Sadat Eshaghi, Sepideh Izadi, Kolsoom Shahdadnejad, Ali Masjedi, Morteza Heydari, Armin Ahmadi, Mohammad Hojjat-Farsangi, Hadi Hassannia, Hamed Mohammadi, Samaneh Boroumand-Noughabi, Mohammad Reza Keramati, Farhad Jadidi-Niaragh
• Journal: Life sciences (Life Sci) Vol. 260 Pg. 118423 (Nov 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 32941896 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• BV6 peptide
• IL6 protein, human
• Interleukin-6
• Oligopeptides
• RNA, Small Interfering
• Lactic Acid
• Polyethylene Glycols
• Chitosan

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Chick Embryo (blood supply, drug effects)
• Chitosan (chemistry)
• Colonic Neoplasms (drug therapy, pathology)
• Drug Delivery Systems (methods)
• Drug Liberation
• Female
• Humans
• Interleukin-6 (antagonists & inhibitors, genetics)
• Lactic Acid (chemistry)
• Magnetic Resonance Spectroscopy
• Mice, Inbred BALB C
• Nanoparticles (administration & dosage, chemistry)
• Neovascularization, Pathologic (drug therapy, pathology)
• Oligopeptides (administration & dosage, pharmacokinetics, pharmacology)
• Polyethylene Glycols (chemistry)
• RNA, Small Interfering (administration & dosage, pharmacokinetics, pharmacology)
• Spectroscopy, Fourier Transform Infrared
• Xenograft Model Antitumor Assays