Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Cancer Therapy

Background:

• Photodynamic therapy (PDT) effectiveness is limited by inflammation-induced therapeutic resistance.
• Cyclooxygenase-2 (COX-2) plays a key role in mediating PDT-induced inflammation.

Purpose of the Study:

• To develop a tumor-homing nanomedicine (NP-Mel) that enhances PDT efficacy by inhibiting COX-2 and suppressing inflammation.
• To improve drug stability, reactive oxygen species (ROS) generation, and targeted delivery for breast cancer treatment.

Main Methods:

• Fabrication of NP-Mel by conjugating protoporphyrin IX (PpIX) and palmitic acid to a neuropilin receptors (NRPs)-targeting peptide, encapsulating meloxicam (a COX-2 inhibitor).
• In vitro and in vivo studies to evaluate NP-Mel's anti-inflammatory effects and therapeutic performance.
• Assessment of prostaglandin E2 (PGE2), IL-6, and TNF-α levels post-PDT treatment.

Main Results:

• NP-Mel demonstrated improved drug stability, ROS production, and targeted delivery to breast cancer cells.
• NP-Mel significantly reduced PGE2 secretion after PDT, leading to downregulation of IL-6 and TNF-α.
• Enhanced antitumor effect of PDT was observed with NP-Mel without significant systemic toxicity.

Conclusions:

• NP-Mel effectively suppresses PDT-induced inflammation by inhibiting COX-2, thereby enhancing antitumor efficacy.
• The developed nanomedicine offers a promising strategy for overcoming therapeutic resistance in PDT.
• This approach may inspire the development of advanced nanomedicines for cancer treatment.