Background: Pathological angiogenesis is a key driver of tumour progression and metastatic spread. Endogenous inhibitors of angiogenesis, including angiostatin and thrombospondin-related proteins, exhibit promising anti-tumour activity but are limited in clinical translation by poor stability and rapid systemic clearance. Biomacromolecular carriers represent a potential strategy to improve the pharmacological performance of protein-based anti-angiogenic therapies.

Methods: A protein-compatible nanoplatform based on human serum albumin was developed and evaluated as a carrier for anti-angiogenic proteins. The system was characterised in terms of physicochemical stability and protein–carrier interactions using standard analytical techniques. Cellular interaction and uptake were assessed in endothelial cell models. Systemic compatibility and short-term in vivo behaviour were evaluated in immunodeficient mice using circulating protein markers and indicators of oxidative stress.

Results: The albumin-based nanoplatform formed stable nanoscale assemblies with favourable physicochemical properties. Carrier–protein interactions supported efficient association of anti-angiogenic proteins and enabled controlled protein retention. In endothelial cell models, the nanoplatform enhanced cellular interaction compared to free proteins, without inducing excessive intracellular degradation. In vivo evaluation demonstrated prolonged systemic presence of albumin-associated formulations compared to unformulated proteins, with no detectable increase in systemic oxidative stress markers.

Conclusions: Albumin-based nanoplatforms offer a biocompatible and stable approach for improving the delivery of anti-angiogenic proteins. These findings support further development of albumin-mediated strategies for adjuvant anti-angiogenic cancer therapy.