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Liver metastases arising from colorectal cancer (CRC) are a major challenge for cancer treatment, as they often emerge as unresectable and resistant to therapy. Novel treatments targeting the specific metastatic tumor microenvironment (TME) may improve the therapeutic outcome. One relevant receptor at the TME in the liver is the endothelial-expressed cell adhesion molecule E-selectin. In this study, we showed in a mouse model of aggressive CT26-derived liver metastasis, that the delivery of otherwise non-effective Doxorubicin via an E-selectin-targeted polymer-peptide-drug conjugate reduced tumor burden of liver metastases and significantly prolonged survival, with ∼50% of mice being tumor-free. In contrast to B16-derived lung metastases, which can successfully be prevented by a "drug-free" E-selectin-blocking copolymer, neither E-selectin-blocking pre-treatment nor the combination with targeted Doxorubicin-delivery proved beneficial against CT26 liver metastasis. In-depth inquiry revealed that E-selectin-blockade by the "drug-free" copolymer reduced E-selectin expression in metastatic livers, but did not prevent CT26 liver colonization, and increased the prevalence of B-cells, possibly indicating an ambiguous role of these cells. However, it did not significantly alter leukocyte migration into the malignant tissue. Overall, targeting E-selectin with nanomedicines is a highly efficient strategy to treat established liver metastases, while the benefit of E-selectin blockade by itself may depend on tumor type and TME-specific factors. [Display omitted] • Colorectal cancer liver metastases of mice regressed upon a single treatment with E-selectin-targeted polymer-drug conjugate. • Overall, 50% of the P-Esbp-Dox treated mice survived with no disease recurrence. • E-selectin blocking copolymer reduced E-selectin expression in metastatic livers but did not affect metastatic growth. • E-selectin is a viable target for drug delivery, but its blockade may have ambiguous effects at the TME. [ABSTRACT FROM AUTHOR]

Diabetic chronic wounds cause a significant amount of pain to patients because of their low cure rates and high recurrence rates. Traditional approaches to treating diabetic chronic wounds often involve the delivery of drugs or cytokines that regulate the microenvironment and eliminate bacterial infection in the wound area, but they are passive in controlling cell behaviors and may lead to drug resistance. Emerging drug-free wound treatments are important for convenient, effective, and safe treatment strategies. However, the current approaches cannot fully promote tissue regeneration or prevent bacterial infections. Here, the efficacy of a negatively charged fiber dressing in promoting diabetic chronic wound healing is investigated. The negatively charged fiber dressing can generate reactive oxygen species to inhibit bacterial reproduction with the assistance of ultrasound during the inflammatory phase. Furthermore, the dressing provides an electrostatic field that regulates cellular behavior during the inflammatory and proliferative phases. In particular, the dressing can promote fibroblast migration and induce macrophage polarization and neovascularization without any additional drugs. It is demonstrated that this strategy enables the healing of diabetic chronic wounds in a mouse model, achieving effective wound closure over a 12-day treatment cycle and providing a drug-free therapeutic strategy for diabetic chronic wound care., (© 2023 Wiley-VCH GmbH.)