Psychobiological correlates of gender and sexual minority stress – Findings from the Swiss LGBTIQ+ panel

Oxaliplatin (Oxa) is the first-line chemotherapeutic drug for the treatment of colorectal cancer (CRC). However, long-term Oxa chemotherapy can induce inflammation and increase the levels of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2), which can promote tumor metastasis. Moreover, high glutathione (GSH) levels in CRC cells significantly reduce Oxa sensitivity and seriously restrict the clinical application of Oxa. Herein, an Oxa (IV) prodrug with anti-inflammatory properties (desmethyl naproxe, DN) and GSH-depleting cyclodextrin pseudo-polyrotaxane carriers were prepared and further self-assembled into micellar nanoparticles (designated [email protected]). The relesae of DN from [email protected] can reduce the level of PGE2 to inhibit inflammation and tumor metastasis by decreasing COX-2 protein, and also synergize with Oxa to inhibit tumor. More importantly, GSH depletion can reduce the detoxification of Oxa and further enhance chemotherapy-induced apoptosis. [email protected] have a good GSH depletion ability to enhance the sensitivity of Oxa, indicating a potential in the synergistic chemotherapy and chemo-sensitization of colorectal cancer.