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Synthesis of Aptamer-PEI-g-PEG Modified Gold Nanoparticles Loaded with Doxorubicin for Targeted Drug Delivery
Published on: June 23, 2020
Nucleotropic doxorubicin nanoparticles decrease cancer cell viability, destroy mitochondria, induce autophagy and
Anna M Friedhuber1, Vijay Chandolu, Somkamon Manchun
1Department of Pathology, University of Melbourne, Melbourne, Australia.
Objective:
Doxorubicin (Dox) is used clinically against various neoplasias, but suffers from serious side effects, and for the past three decades, this shortcoming has spurred research towards finding better drug delivery systems (DDSs) for this frontline drug.
Methods:
A non-targeted nucleotropic Dox-loaded nanoparticle (DNP) DDS is described, which has a simple chemical design, is easy to formulate and administer, is inexpensive, non-biohazardous and may prove to be useful clinically.
Key Findings:
The DNP formulated via vortex-assisted complex coarcevation enhanced (300-fold) cell-inhibitory activity of the drug in a panel of human cancer cells (osteosarcoma, breast, prostate and colorectal cancer) and enhanced (10-fold) efficacy against osteosarcoma (OS) in vivo. The slow-release DNPs localised to the endoplasmic reticulum disrupted the mitochondria and entered the nucleus. Prominent cytosolic vacuolisation, budding off of portions of the cytoplasm, both suggestive of autophagy, were observed. Mice that were administered with DNPs intratumorally had the smallest tumours at the end of the study, with more necrotic hotspots.
Conclusion:
This promising nucleotropic DDS enhances the cell delivery and activity of Dox against a variety of human cancer cell lines and in OS tumours in mice.
Insights
A novel nanoparticle drug delivery system (DNP) significantly boosts doxorubicin
Area of Science:
- Nanotechnology
- Drug Delivery Systems
- Oncology
Background:
- Doxorubicin (Dox) is a vital chemotherapy drug for various cancers.
- Significant side effects limit Doxorubicin's clinical use.
- Developing advanced drug delivery systems (DDSs) for Doxorubicin is crucial.
Purpose of the Study:
- To develop and evaluate a novel nucleotropic Doxorubicin-loaded nanoparticle (DNP) DDS.
- To assess the DNP's efficacy in enhancing Doxorubicin's anti-cancer activity.
- To investigate the DNP's mechanism of action and in vivo performance.
Main Methods:
- Formulation of Doxorubicin-loaded nanoparticles (DNPs) using vortex-assisted complex coacervation.
- In vitro evaluation of DNP's cell-inhibitory activity against human cancer cell lines.
- In vivo assessment of DNP's anti-tumor efficacy in a mouse model of osteosarcoma.
Main Results:
- DNPs demonstrated a 300-fold enhancement in cell-inhibitory activity against multiple cancer cell lines.
- In vivo studies showed a 10-fold increase in efficacy against osteosarcoma.
- DNPs localized to the endoplasmic reticulum, disrupted mitochondria, and entered the nucleus, inducing autophagy.
Conclusions:
- The developed nucleotropic DNP DDS is a promising, cost-effective, and non-biohazardous approach.
- DNPs significantly enhance Doxorubicin's delivery and anti-cancer activity.
- This DDS holds potential for improved clinical application in treating various cancers.
More Related Videos
10:26Using In Vitro Live-cell Imaging to Explore Chemotherapeutics Delivered by Lipid-based Nanoparticles
Published on: November 1, 2017
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
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