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Clinical Orthopaedics and Related Research®

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01-03-2013 | Symposium: Highlights from the First Combined 2011 Meeting of the Musculoskeletal Tumor Society and Connective Tissue Oncology Society

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Authors: Eisuke Kobayashi, MD, PhD, Arun K. Iyer, PhD, Francis J. Hornicek, MD, PhD, Mansoor M. Amiji, PhD, Zhenfeng Duan, MD, PhD

Published in: Clinical Orthopaedics and Related Research® | Issue 3/2013

Abstract

Background

The toxicity of anticancer agents and the difficulty in delivering drugs selectively to tumor cells pose a challenge in overcoming multidrug resistance (MDR). Recently, nanotechnology has emerged as a powerful tool in addressing some of the barriers to drug delivery, including MDR in cancer, by utilizing alternate routes of cellular entry and targeted delivery of drugs and genes. However, it is unclear whether doxorubicin (Dox) can be delivered by nanotechnologic approaches.

Questions/Purposes

We asked whether (1) Dox-loaded lipid-functionalized dextran-based biocompatible nanoparticles (Dox/NP) can reverse MDR, (2) Dox/NP has more potent cytotoxic effect on MDR tumors than poly(ethylene glycol)-modified liposomal Dox (PLD), and (3) multidrug resistance protein 1 (MDR1) small interfering RNA loaded in these nanoparticles (siMDR1/NP) can modulate MDR.

Methods

To create stable Dox/NP and siMDR1/NP, we used two different lipid-modified dextran derivatives. The effect of Dox or Dox/NP was tested on drug-sensitive osteosarcoma (KHOS) and ovarian cancer (SKOV-3) cell cultures in triplicate and their respective MDR counterparts KHOS_R2 and SKOV-3_TR in triplicate. We determined the effects on drug retention, transfection efficacy of siMDR1/NP, and P-glycoprotein expression and the antiproliferative effect between Dox/NP and PLD in MDR tumor cells.

Results

Fluorescence microscopy revealed efficient uptake of the Dox/NP and fluorescently tagged siMDR1/NP. Dox/NP showed five- to 10-fold higher antiproliferative activity at the 50% inhibitory concentration than free Dox in tumor cells. Dox/NP showed twofold higher activity than PLD in MDR tumor cells. siMDR1/NP (100 nM) suppressed P-glycoprotein expression in KHOS_R2.

Conclusions

Dextran-lipid nanoparticles are a promising platform for delivering Dox and siRNAs.

Clinical Relevance

Biocompatible dextran-based nanoparticles that are directly translatable to clinical medicine may lead to new potential therapeutics for reversing MDR in patients with cancer.

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Title: Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study
Authors: Eisuke Kobayashi, MD, PhD
Arun K. Iyer, PhD
Francis J. Hornicek, MD, PhD
Mansoor M. Amiji, PhD
Zhenfeng Duan, MD, PhD
Publication date: 01-03-2013
Publisher: Springer-Verlag
Published in: Clinical Orthopaedics and Related Research® / Issue 3/2013
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-012-2610-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Lipid-functionalized Dextran Nanosystems to Overcome Multidrug Resistance in Cancer: A Pilot Study

Abstract

Background

Questions/Purposes

Methods

Results

Conclusions

Clinical Relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Questions/Purposes

Methods

Results

Conclusions

Clinical Relevance

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