Targeted paclitaxel delivery to tumors using cleavable PEG-conjugated solid lipid nanoparticles

Area of Science:

• Nanotechnology
• Materials Science
• Oncology

Background:

• Solid lipid nanoparticles (SLNs) are a promising drug delivery platform.
• Targeted delivery systems can improve therapeutic efficacy and reduce side effects.
• Matrix metalloproteinases (MMPs) are over-expressed in many tumors, presenting a target for drug delivery.

Purpose of the Study:

• To develop paclitaxel-loaded SLNs conjugated with an MMP-cleavable peptide (Pp-PTX-SLNs) for enhanced tumor targeting.
• To evaluate the physicochemical properties, in vitro performance, and in vivo anti-tumor activity of the developed system.

Main Methods:

• Paclitaxel-loaded SLNs were prepared and conjugated with a PEGylated peptide (Pp).
• Physicochemical characteristics, in vitro drug release, cytotoxicity, and cell uptake were assessed.
• Pharmacokinetics, biodistribution, and anti-tumor efficacy were evaluated in a tumor-bearing mice model.

Main Results:

• Pp-PTX-SLNs demonstrated efficient uptake by tumor cells via MMP-mediated mechanisms.
• In vivo studies showed enhanced tumor accumulation, prolonged circulation, and reduced toxicity compared to non-targeted SLNs and Taxol®.
• Mice treated with Pp-PTX-SLNs exhibited significantly improved survival rates.

Conclusions:

• MMP-targeted SLNs represent a novel and effective strategy for paclitaxel chemotherapy.
• The Pp-SLN system holds potential as a versatile nanocarrier for various chemotherapeutic agents.