5-fluorouracil-loaded mesoporous copper-coated manganese dioxide nanoparticles for synergistic photothermal and chemotherapy in 5-FU-resistant colon cancer.

Nanoplatforms engineered for targeted delivery are crucial for improving tumor treatment by concentrating chemotherapy in tumors, improving drug solubility/efficacy, enabling personalized therapies, and reducing systemic toxicity. We present a nanoplatform (MCuS/5FU/IG@MnO2@S100A8/A9 (MCFIMS)) that synergistically improves chemodynamic therapy (CDT), photothermal therapy (PTT), photodynamic treatment (PDT), and chemotherapy. The nanoplatform comprises dual-shell MC@M NPs that enable targeted delivery of the chemotherapeutic drug 5-Fluorouracil (5FU) and the photosensitizer indocyanine green (IG). These MCFIMS NPs enhance the chemotherapeutic efficiency of 5FU by effectively using glutathione (GSH). The integration of the colon-targeting peptide (S100A8/A9) enables the nanoplatform to deliver receptor-mediated targeting to colon cancer cells. Significantly, when paired with near-infrared (NIR) light, MCFIMS exhibited an extraordinary tumor proliferation. Overall, this nanoplatform possesses nuclear-targeting ability, facilitating the concentration of chemotherapeutic drugs at tumor sites of proliferation, and shows promise for synergistic applications to augment chemotherapy in 5FU-resistant colon cancer cells.