Poly(aspartic acid)-based pH-responsive targeting co-delivery nanoparticles

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Drug Delivery

Background:

• Nanocarrier encapsulation enhances therapeutic molecule delivery for effective cancer treatment.
• Dual-agent delivery systems offer synergistic therapeutic effects.
• pH-responsive and actively targeted nanocarriers are crucial for precise cancer therapy.

Purpose of the Study:

• To prepare pH-responsive, dual-agent loaded nanoparticles for enhanced cancer treatment.
• To evaluate the physicochemical properties, drug loading, and anticancer efficacy of the novel nanocarrier.
• To investigate the cellular uptake mechanism and targeting capability of the nanocarrier.

Main Methods:

• Synthesis of hyaluronic acid-ethylenediamine-poly(aspartic acid)-tyrosine (HA-EDA-PASP-Tyr or HEPT) nanocarriers.
• Encapsulation of doxorubicin hydrochloride (DOX) and curcumin (CUR) into HEPT nanoparticles.
• Characterization of particle size, morphology, and pH-responsive behavior.
• In vitro cytotoxicity assays and confocal laser scanning microscopy for cellular uptake studies.

Main Results:

• HEPT nanoparticles exhibited high loading capacity for both DOX (26.0±1.9%) and CUR (50.9±4.3%).
• Nanoparticles showed pH-responsive swelling and morphological changes in acidic conditions.
• Co-loaded (DOX+CUR)@HEPT nanoparticles demonstrated significantly higher cytotoxicity against HCT-116 cells compared to free drugs.
• Hyaluronic acid ligand facilitated enhanced cellular uptake via active targeting.

Conclusions:

• The developed HEPT nanocarrier system effectively co-delivers DOX and CUR with high loading efficiency.
• The pH-responsive and actively targeted nanoparticles exhibit superior in vitro anticancer efficacy.
• This dual-drug delivery system presents a promising strategy for advanced cancer therapy.