Phosphorus Dendrimer-Mediated Protein Delivery

Phosphorus dendrimers represent a next-generation nanoplatform that has garnered increasing attention for delivering diverse protein therapeutics. Compared with conventional organic and inorganic protein carriers, phosphorus dendrimers possess distinct advantages, including intrinsic bioactivity, well-defined molecular architecture, multimodal protein-loading mechanisms, considerable structural modifiability, reliable stability, and desired biocompatibility, realizing simple and mild protein complexation merely through physical interactions to construct phosphorus dendrimer-based protein nanomedicines. Recent studies have demonstrated the synergistic therapeutic enhancement against multiple diseases, such as osteoarthritis, cancer, ischemic stroke, Alzheimer's disease, and Parkinson's disease, based on these nanomedicines. In this Perspective, the primary synthesis routes of phosphorus dendrimers are systematically outlined at first, and their superiority as protein nanoplatforms over other carriers is comparatively analyzed. Then, the latest advances of the above nanomedicines in disease therapies are summarized in detail, and the current challenges hindering their applications from bench to bedside are also discussed.