ArticleClinical orthopaedics and related research2013
Lipid-functionalized dextran nanosystems to overcome multidrug resistance in cancer: a pilot study.
Article in Clinical orthopaedics and related research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 42 citations in OpenAlex.
- Enhanced safety and efficacy profile of CD40 antibody upon encapsulation in pHe-triggered membrane-adhesive nanoliposomes.Nanomedicine (London, England) · 2025Article
- Copper-Free 'Click' Chemistry-Based Synthesis and Characterization of Carbonic Anhydrase-IX Anchored Albumin-Paclitaxel Nanoparticles for Targeting Tumor Hypoxia.International journal of molecular sciences · 2018Article
- NVP-TAE684 reverses multidrug resistance (MDR) in human osteosarcoma by inhibiting P-glycoprotein (PGP1) function.British journal of pharmacology · 2016Article
- Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases.The AAPS journal · 2015Review
- Cosilencing of PKM-2 and MDR-1 Sensitizes Multidrug-Resistant Ovarian Cancer Cells to Paclitaxel in a Murine Model of Ovarian Cancer.Molecular cancer therapeutics · 2015Article
- Polymeric nanoparticle-based delivery of microRNA-199a-3p inhibits proliferation and growth of osteosarcoma cells.International journal of nanomedicine · 2015Article
- Article
- Prevention of multidrug resistance (MDR) in osteosarcoma by NSC23925.British journal of cancer · 2014Article
- Molecular mechanisms of chemoresistance in osteosarcoma (Review).Oncology letters · 2014Article
- Lipid nanotechnology.International journal of molecular sciences · 2013Article
- Nanomaterials as Non-viral siRNA Delivery Agents for Cancer Therapy.BioImpacts : BI · 2013Article
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5 authors at 3 institutions in 1 country.
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Abstract
backgroundThe 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.
methodsTo 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.
resultsFluorescence 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).
conclusionsDextran-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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