Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2

作者：Zhang, Wei; Yu, Bai-Xue; Chen, Xia-Yun; Yan, Meng-Yi; Liu, Qian-Qian; Liu, Yi-Bin; Yang, Ni; Cai, Hua; Yan, Ni; Kong, Ren-Jiang; Cheng, Hong^*; Li, Shi-Ying^*; Chen, A-Li^*

来源：Small, 2024.

DOI：10.1002/smll.202309882

• anti-inflammation
• cyclooxygenase-2 (COX-2)
• neuropilin receptors (NRPs) targeting
• photodynamic therapy
• prostaglandin E2 (PGE2)

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-alpha expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance. @@@ Tumor homing chimeric peptide rhomboids (designated as NP-Mel) are developed to promote the targeting delivery of drugs to breast cancer overexpressing neuropilin receptors (NRPs). NP-Mel decrease the secretion of prostaglandin E2 (PGE2) after photodynamic therapy (PDT), inducing the downregulation of pro-inflammatory cytokines to reverse PDT induced inflammation for enhanced breast cancer treatment. image

• 单位
  5; 广东药学院; 广州医学院; 南方医科大学