Novel folate-targeted docetaxel-loaded nanoparticles for tumour targeting: in vitro and in vivo evaluation

Abstract

Cholesterol-PEG₁₀₀₀ (Chol-PEG) has shown great potential in drug delivery. In our work, the synthesis of Chol-PEG₁₀₀₀-FA (folic acid) was firstly achieved via an amide reaction of NH₂ on the surface of Chol-PEG₁₀₀₀-NH₂, and then docetaxel-loaded Chol-PEG₁₀₀₀-FA nanoparticles were prepared by the precipitation–ultrasonication combined high-pressure homogenization (HPH) technique, and were characterized by particle size, zeta potential and morphology; meanwhile the average drug loading of the resulting DTX/Chol-PEG₁₀₀₀-FA nanoparticles reached up to 68%. The anti-tumor efficiency and targeting ability of docetaxel-loaded Chol-PEG₁₀₀₀-FA nanoparticles (DTX-FA-Nps) were demonstrated by their in vitro and in vivo anti-tumor activity against 4T1 cells. The docetaxel-loaded Chol-PEG₁₀₀₀ nanoparticles with and without FA conjugation proved to be of satisfactory size and distribution, with favorable drug release and high drug encapsulation efficiency. In vitro results showed the higher anti-tumor efficiency of the DTX-FA-Nps and DTX-Nps (docetaxel-loaded Chol-PEG₁₀₀₀ nanoparticles) than docetaxel solutions (DTX-Sol). The tumor-targeting effects of the FA conjugated Chol-PEG₁₀₀₀ are also studied. The IC₅₀ values of DTX-Sol, DTX-Nps and DTX-FA-Nps are 1.6260, 0.3772 and 0.0171 μg mL⁻¹, respectively, for 4T1 cancer cells after 48 h of treatment. The inhibition rate for the DTX-FA-Nps at 10 mg kg⁻¹ was 74.83% (P < 0.01). Based on these results, the DTX-loaded Chol-PEG₁₀₀₀-FA nanoparticles may be a promising targeted delivery system for breast cancer therapy.