Related Experiment Video
Updated: Jun 2, 2025
Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
Core-Shell Nanoparticles with Sequential Drug Release Depleting Cholesterol for Reverse Tumor Multidrug Resistance
Jieke Zhang1, Yingying Zhou1, Jialing Guo1
1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Abstract:
Multidrug resistance (MDR) facilitates tumor recurrence and metastasis, which has become a main cause of chemotherapy failure in clinical. However, the current therapeutic effects against MDR remain unsatisfactory, mainly hampered by the rigid structure of drug-resistant cell membranes and the uncontrolled drug release. In this study, based on a sequential drug release strategy, we engineered a core-shell nanoparticle (DOX-M@CaP@ATV@HA) depleting cholesterol for reverse tumor MDR. DOX-M@CaP@ATV@HA could accurately target tumor cells due to the active targetability of hyaluronic acid (HA) toward CD44 receptors. The calcium phosphate (CaP) shell was cleaved in the lysosomal acidic environment so that the cholesterol-lowering drug atorvastatin (ATV) was rapidly released to diminish cholesterol and P-glycoprotein (P-gp) level on the membrane, thereby boosting tumor cell drug uptake. Next, doxorubicin (DOX) was gradually released from the hydrophobic core of the mPEG-DSPE micelle, inflicting irreversible DNA damage and triggering apoptosis. The nanosystem was proven both in vitro and in vivo to reverse MDR effectively and exhibited a remarkable therapeutic efficacy on drug-resistant tumors with high biosafety. In conclusion, DOX-M@CaP@ATV@HA effectively reverses MDR via cholesterol depletion, which provides an innovative strategy for tumor MDR treatment.
Insights
This study introduces a novel nanoparticle (DOX-M@CaP@ATV@HA) that reverses multidrug resistance (MDR) in tumors by depleting cholesterol. This innovative strategy enhances chemotherapy effectiveness against drug-resistant cancers.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug resistance (MDR) is a major cause of chemotherapy failure, driven by factors like rigid cell membranes and uncontrolled drug release.
- Current treatments for MDR lack efficacy, necessitating innovative therapeutic strategies.
Purpose of the Study:
- To engineer a core-shell nanoparticle (DOX-M@CaP@ATV@HA) for sequential drug release to overcome tumor MDR.
- To investigate the potential of cholesterol depletion as a strategy to reverse MDR.
Main Methods:
- Development of a core-shell nanoparticle (DOX-M@CaP@ATV@HA) with hyaluronic acid (HA) for targeted delivery.
- Sequential release of atorvastatin (ATV) to deplete cholesterol and P-glycoprotein (P-gp), followed by doxorubicin (DOX) release for apoptosis induction.
- In vitro and in vivo evaluation of the nanosystem's efficacy in reversing MDR and treating drug-resistant tumors.
Main Results:
- The nanoparticle (DOX-M@CaP@ATV@HA) demonstrated targeted delivery to tumor cells via HA-CD44 interaction.
- Rapid release of ATV from the calcium phosphate (CaP) shell reduced cellular cholesterol and P-gp levels, enhancing drug uptake.
- Gradual release of DOX from the core induced DNA damage and apoptosis, effectively reversing MDR.
- The nanosystem showed significant therapeutic efficacy against drug-resistant tumors with high biosafety in both in vitro and in vivo studies.
Conclusions:
- The engineered nanosystem (DOX-M@CaP@ATV@HA) effectively reverses tumor MDR through a sequential drug release strategy involving cholesterol depletion.
- This approach offers a promising and innovative therapeutic strategy for treating drug-resistant cancers.
More Related Videos
09:34Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
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
