Engineering Thermo/pH-Responsive Lactoferrin Nanostructured Microbeads for Oral Targeting of Colorectal Cancer

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Colorectal cancer (CRC) is a deadly malignancy with limited oral treatment options.
• Lactoferrin (LF) shows promise for CRC therapy, but oral delivery is challenging.
• Existing delivery systems face hurdles in targeting and efficacy.

Purpose of the Study:

• To engineer dual-responsive lactoferrin nanostructured microbeads for enhanced oral delivery of CRC therapeutics.
• To overcome the limitations of oral drug delivery for colorectal cancer treatment.
• To improve drug targeting and therapeutic outcomes in CRC.

Main Methods:

• Amphiphilic conjugate nanoparticles were formed by coupling mesalazine (MSZ) to lactoferrin (LF).
• Resveratrol (RSV) was encapsulated into LF-MSZ nanoparticles, which were then coated with a thermoresponsive PNIPAAm shell.
• Nanoparticles were microencapsulated into pectin-alginate beads for gastrointestinal resistance and pH responsiveness.

Main Results:

• Nanoparticles demonstrated enhanced internalization and cytotoxicity in HCT colon cancer cells via LF-receptor-mediated endocytosis.
• The microbeads exhibited temperature-triggered release and protected encapsulated drugs from degradation.
• Oral administration in a mouse model significantly reduced tumor burden, modulated tumor markers, and induced apoptosis.

Conclusions:

• Lactoferrin nanostructured microbeads represent a promising, innovative approach for oral colorectal cancer therapy.
• This dual-responsive system overcomes oral delivery challenges, offering a paradigm shift in CRC treatment.
• The engineered microbeads show significant therapeutic potential in preclinical settings.