Multifunctional pH-sensitive polymeric nanoparticles for theranostics evaluated experimentally in cancer

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Multifunctional nanoparticles are crucial for integrated cancer diagnosis and therapy.
• Targeted drug delivery and imaging agents can improve therapeutic outcomes and reduce side effects.
• pH-sensitive materials offer potential for controlled drug release in tumor microenvironments.

Purpose of the Study:

• To develop a multifunctional pH-sensitive polymeric nanoparticle system for simultaneous tumor MRI and therapy.
• To evaluate the targeting, drug release, antitumor efficacy, and MRI performance of the developed nanoparticles.
• To assess the biocompatibility of the theranostic nanoparticles.

Main Methods:

• Self-assembly of PLA-PEG-PLL-DTPA and PLH-PEG-biotin polymers to form nanoparticles.
• Encapsulation of sorafenib and chelation of Gd ions for drug delivery and MRI contrast.
• Surface functionalization with VEGFR antibodies for active targeting.
• In vitro and in vivo evaluation of pH-sensitive drug release, cytotoxicity, antitumor activity, and MRI performance.

Main Results:

• Developed target pH-sensitive theranostic nanoparticles (TPTN) with high encapsulation efficiency and drug loading.
• Demonstrated pH-sensitive sorafenib release, with significantly higher release at pH 5.0 compared to pH 7.4.
• TPTN showed comparable in vitro cytotoxicity to sorafenib solution and significantly higher in vivo antitumor efficacy in tumor-bearing mice.
• TPTN exhibited enhanced MRI contrast with higher T1 relaxivity and longer imaging time compared to Magnevist®.
• Histological examination confirmed good biocompatibility with no visible tissue toxicity.

Conclusions:

• TPTN is a promising multifunctional theranostic platform for simultaneous tumor imaging and therapy.
• The nanoparticle system integrates active targeting, pH-triggered drug release, and MRI capabilities.
• TPTN demonstrates superior in vivo antitumor efficacy and diagnostic potential for hepatocellular carcinoma.