Dual pH/redox-responsive size-switchable polymeric nano-carrier system for tumor microenvironment DTX release

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Chemotherapeutic nano drug delivery systems (NDDSs) offer promising cancer therapy strategies.
• Tumor microenvironment (TME) characteristics like low pH and high glutathione (GSH) present unique targeting opportunities.

Purpose of the Study:

• To design and evaluate novel TME-targeted, pH/redox dual-responsive nanoparticles (NPs) for deep tumor penetration and targeted anti-tumor therapy.
• To leverage the TME's specific conditions for enhanced drug delivery and efficacy.

Main Methods:

• Synthesized dual-responsive P(AMA-co-DMAEMA)-b-PCL-SS-PCL-b-P(AMA-co-DMAEMA) nanoparticles.
• Investigated nanoparticle size changes, cellular uptake, and drug release kinetics within simulated TME conditions.
• Assessed anti-tumor efficacy using docetaxel (DTX)-loaded NPs in MDA-MB-231 cells, analyzing cell cycle, apoptosis, and gene/protein expression.

Main Results:

• Positively charged NPs demonstrated enhanced cellular uptake due to electrostatic interactions.
• NPs exhibited a significant size reduction (98.24 nm to 45.56 nm) in the TME, improving deep tumor penetration via the EPR effect.
• Achieved pH/redox-triggered drug release (~70% at 24h) with no observed toxicity and significant G2/M cell cycle arrest (84.6%).
• DTX-loaded NPs induced higher apoptosis (62.6%) compared to free DTX (51.8%) and significantly upregulated apoptotic gene/protein expression (P<0.001).

Conclusions:

• The developed size-shrinkable, TME-targeted nanoparticles show significant potential for improving chemotherapy delivery and efficacy.
• This novel NDDS holds promise for advanced, targeted anti-cancer therapeutic strategies.