Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for Drug Delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Targeted drug delivery aims to improve therapeutic efficacy and reduce side effects.
• Folate receptor-mediated endocytosis is a promising pathway for cancer cell targeting.
• pH-responsive materials can control drug release in specific cellular environments.

Purpose of the Study:

• To develop multifunctional, pH-responsive, folate-targeted polymer nanoparticles (TPNps) for docetaxel (DTX) delivery.
• To evaluate the physicochemical properties, drug loading, and in vitro/in vivo performance of the TPNps.
• To investigate the cellular uptake mechanisms and anti-tumor efficacy of DTX-loaded TPNps.

Main Methods:

• Synthesis of P123-PAE and P123-FA copolymers for nanoparticle formulation.
• Loading of docetaxel (DTX) into TPNps and characterization of drug loading content.
• In vitro drug release studies at different pH values (pH 5.5 and 7.4).
• Cytotoxicity assessment using MTT assay on MCF-7 cells.
• Cellular uptake studies using flow cytometry and confocal microscopy.
• In vivo pharmacokinetic studies to evaluate drug retention time.

Main Results:

• TPNps successfully loaded DTX with a drug loading content of 15.02 ± 0.14 wt%.
• DTX release from TPNps exhibited pH-dependent behavior, with higher release at pH 5.5.
• Blank nanoparticles showed minimal toxicity; DTX-loaded TPNps demonstrated significant anti-tumor activity (IC50 = 0.72 μg/mL) against MCF-7 cells.
• TPNps showed enhanced cellular uptake compared to non-targeted nanoparticles, via folate receptor-mediated endocytosis.
• Cellular uptake and killing effects were approximately doubled at pH 5.5 versus pH 7.4.
• TPNps significantly prolonged the in vivo retention time of DTX.

Conclusions:

• The developed pH-responsive, folate-modified polymer nanoparticles are biocompatible and effective for targeted intracellular delivery of DTX.
• These TPNps offer a promising nanosystem for enhancing the efficacy of docetaxel chemotherapy.
• The pH-responsive and targeting features contribute to improved drug delivery and anti-tumor effects.