A polycation coated liposome as efficient siRNA carrier to overcome multidrug resistance
Yuqiong Xia1, Xiaofei Wang1, He Cheng1
1School of Life Science and Technology, Xidian University, Xi'an, Shaanxi, 710126, China.
Abstract:
Multidrug resistance (MDR) is one of the important factors that impede effective chemotherapy against cancer. Codelivery of MDR1 siRNA (silencing ABCB1 gene) and anticancer drug can greatly inhibit tumor proliferation. Here in this work, we synthesized poly(diallyldimethylammonium chloride) (PDADMAC) coated liposome formula as siMDR1 carrier (AL-PDAD-RNA) and applied it to reverse doxorubicin resistance of OVCAR8/ADR cells. The AL-PDAD-RNA can load siRNA effectively and release siRNA under physiological conditions, leading to improved tumor inhibition than free DOX without siRNA treatment. Meanwhile, the gene silencing effect of AL-PDAD-RNA was shown to be comparable to that of commercial transfection agent lipofectamine, but with less toxicity. The main novelty of this work is to offer a new type of siRNA carrier (PDADMAC coated liposome, AL-PDAD), which is simple-structured, highly-effective and non-toxic. Therefore, we anticipate that PDADMAC-coated liposomes would be very promising in the application of other siRNA delivery or even plasmid delivery.
Insights
This study introduces a novel, non-toxic poly(diallyldimethylammonium chloride) (PDADMAC) coated liposome for delivering multidrug resistance (MDR) siRNA and anticancer drugs, effectively inhibiting tumor growth and overcoming chemotherapy resistance.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Multidrug resistance (MDR) significantly hinders effective cancer chemotherapy.
- Codelivery of MDR1 siRNA and anticancer drugs shows potential for inhibiting tumor proliferation.
Purpose of the Study:
- To develop and evaluate a novel poly(diallyldimethylammonium chloride) (PDADMAC) coated liposome (AL-PDAD-RNA) as a carrier for MDR1 siRNA.
- To assess the efficacy of AL-PDAD-RNA in reversing doxorubicin resistance in OVCAR8/ADR cells.
Main Methods:
- Synthesis of PDADMAC-coated liposomes (AL-PDAD) for siRNA loading.
- Evaluation of siRNA loading capacity and release under physiological conditions.
- In vitro assessment of doxorubicin resistance reversal and gene silencing efficacy compared to commercial agents.
Main Results:
- AL-PDAD-RNA effectively loaded and released siRNA under physiological conditions.
- Codelivery of doxorubicin and siRNA via AL-PDAD-RNA demonstrated improved tumor inhibition compared to free doxorubicin.
- The gene silencing effect of AL-PDAD-RNA was comparable to lipofectamine but exhibited lower toxicity.
Conclusions:
- PDADMAC-coated liposomes represent a simple, highly effective, and non-toxic siRNA carrier.
- This novel carrier system shows promise for overcoming multidrug resistance in cancer therapy.
- PDADMAC-coated liposomes have potential applications in siRNA and plasmid delivery for various therapeutic strategies.
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