Amplified Drug Delivery System with a Pair of Master Keys Triggering Precise Drug Release for Chemo-Photothermal
Sujuan Ye1, Longfei Ma1, Jihua Zhang1
1Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE; Shandong Key Laboratory of Biochemical Analysis; College of Chemistry and Molecular Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, P. R. China.
Abstract:
A versatile drug delivery system (DDS) enabling highly effective and targeting oncotherapy has always been of great significance in medical research. In the development of a stimuli-responsive DDS, compared with a single-factor stimulation DDS, a multifactor activation DDS has higher therapeutic specificity between diseased and normal tissue, but there are challenges in drug-release efficiency and united targeting cancer therapy. Herein, a novel dual-microRNA (dual-miRNA)-mediated 1:N-amplified DDS is fabricated. The gold nanocage (AuNC) was synthesized and used as a carrier. A DNA bridge motif as a nanolock (DNA bridge nanolock) was designed and modified on the surface of AuNCs, which could seal the holes of AuNCs. Using the dual-miRNAs as a pair of master keys, through DNA strand migration and DNAzyme self-assembly, a cell endogenous substance Mg2+-dependent DNAzyme cyclic shear reaction could perform the function of the master keys to open multiple locks for the enhanced release of doxorubicin from the AuNCs. In addition, under near-infrared irradiation, via absorption of light and heat release, the AuNC is activated to perform the function of photothermal therapy. Thereby, the system achieves precise chemo-photothermal therapy. Using the in vitro and in vivo anti-tumor analysis, the DDS could be proved to present a novel design of enhanced and targeted drug-release system for highly effective cancer therapy.
Insights
This study introduces a novel dual-microRNA-activated drug delivery system (DDS) for enhanced cancer therapy. The system amplifies drug release and combines chemotherapy with photothermal therapy for improved targeting and effectiveness.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Stimuli-responsive drug delivery systems (DDS) are crucial for effective cancer therapy.
- Multifactor activation DDS offer higher specificity but face challenges in drug release and unified targeting.
- Developing advanced DDS for targeted oncotherapy remains a significant research area.
Purpose of the Study:
- To fabricate a novel dual-microRNA (dual-miRNA)-mediated 1:N-amplified DDS for enhanced and targeted cancer therapy.
- To integrate chemotherapy with photothermal therapy for precise cancer treatment.
- To overcome limitations in drug-release efficiency and unified targeting in stimuli-responsive DDS.
Main Methods:
- Synthesis of gold nanocages (AuNCs) as drug carriers.
- Modification of AuNCs with a DNA bridge nanolock mechanism.
- Utilizing dual-miRNAs as triggers for DNA strand migration and DNAzyme self-assembly.
- Employing a Mg2+-dependent DNAzyme cyclic shear reaction for amplified drug release.
- Activating AuNCs with near-infrared irradiation for photothermal therapy.
Main Results:
- The fabricated DDS demonstrated enhanced and amplified release of doxorubicin.
- The dual-miRNA system effectively opened the nanolock, facilitating drug release.
- AuNCs successfully performed photothermal therapy upon near-infrared irradiation.
- In vitro and in vivo anti-tumor analyses confirmed the DDS's efficacy.
Conclusions:
- The developed dual-miRNA-mediated DDS offers a novel design for enhanced and targeted drug release.
- The system achieves precise chemo-photothermal therapy, improving cancer treatment efficacy.
- This DDS presents a promising platform for highly effective oncotherapy.
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