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pH/redox responsive size-switchable intelligent nanovehicle for tumor microenvironment targeted DOX release
Fahimeh Badparvar1, Ahmad Poursattar Marjani2, Roya Salehi3
1Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, Iran.
Scientific Reports
|December 18, 2023
Summary
New copolymeric nanoparticles precisely deliver cancer drugs to tumor cells. These dual pH/redox-responsive nanoparticles show enhanced cell uptake and anti-tumoral effects, offering a promising platform for targeted cancer therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- The tumor microenvironment (TME) presents challenges for targeted drug delivery.
- Developing strategies to control drug release within tumor cells is crucial for enhanced efficacy.
- Site-specific drug delivery aims to improve therapeutic outcomes while minimizing systemic toxicity.
Purpose of the Study:
- To design and synthesize novel copolymeric nanoparticles with size-switchable ability and dual pH/redox-triggered drug release.
- To evaluate the efficacy of these nanoparticles for site-specific doxorubicin (DOX) delivery in MDA-MB-231 tumor cells.
- To investigate the anti-tumoral effects of DOX-loaded nanoparticles compared to free DOX.
Main Methods:
- Synthesis of (PAA-b-PCL-S-S-PCL-b-PAA) copolymeric nanoparticles.
- Characterization of nanoparticle size and surface charge changes in the TME.
- Assessment of cellular uptake and drug release kinetics.
- Cell cycle analysis and apoptosis assays.
- Gene and protein expression analysis using Western blot and RT-PCR.
Main Results:
- Nanoparticles exhibited significant cell internalization (~100% at 30 min) and dual pH/redox-responsive drug release.
- Nanoparticle size decreased from 170.3 nm to 93 nm, and surface charge shifted from -17.8 to -2.4 in the TME.
- DOX-loaded nanoparticles induced G2/M cell cycle arrest (68%) and higher apoptosis (71.6%) compared to free DOX.
- Upregulation of apoptotic genes and proteins was significantly higher with DOX-loaded nanoparticles (P<0.001).
Conclusions:
- Dual pH/redox-responsive and size-switchable nanoparticles demonstrate superior anti-tumoral activity compared to free DOX.
- These nanoparticles represent a promising platform for tumor site-specific drug accumulation and controlled release.
- Further in vivo research is warranted to validate the therapeutic potential of this novel drug delivery system.
