PH and redox dual-responsive polymeric micelles with charge conversion for paclitaxel delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Tumor microenvironments are characterized by lower pH and higher glutathione (GSH) concentrations.
• Traditional drug delivery systems often struggle with efficient tumor targeting and intracellular drug release.
• Developing stimuli-responsive nanocarriers is crucial for overcoming these limitations.

Purpose of the Study:

• To develop and characterize dual-responsive micelles for enhanced drug delivery.
• To investigate the pH and redox responsiveness of methoxypoly(ethylene glycol)-cystamine-poly(L-glutamic acid)-imidazole (mPEG-SS-PGA-IM) micelles.
• To evaluate the in vitro efficacy of paclitaxel (PTX)-loaded micelles in cancer cells.

Main Methods:

• Self-assembly of amphiphilic polymer mPEG-SS-PGA-IM in aqueous solution.
• Evaluation of micelle charge conversion at tumor-relevant pH.
• Assessment of endo/lysosomal escape via proton sponge effect and GSH-mediated degradation.
• Confocal laser scanning microscopy (CLSM) for cellular uptake studies.
• MTT assay to determine cytotoxicity of PTX-loaded micelles.

Main Results:

• mPEG-SS-PGA-IM micelles demonstrated pH-dependent charge conversion, facilitating cellular uptake.
• Micelles successfully escaped endo/lysosomes and entered the cytoplasm, confirmed by CLSM.
• PTX-loaded mPEG-SS-PGA-IM micelles exhibited significantly higher cytotoxicity against HCT116 cells compared to control micelles.
• The dual-responsive nature of the micelles was confirmed by their degradation in the presence of GSH.

Conclusions:

• mPEG-SS-PGA-IM micelles are effective pH- and redox-responsive nanocarriers.
• These micelles show potential for improving drug targeting efficiency in tumors.
• The developed nanocarriers can enhance the antitumor efficacy of paclitaxel, offering a promising strategy for cancer therapy.