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Life sciences · Journal article
Biomacromolecules · October 7, 2026
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Abstract Over the past decade, nanogels (NGs) have emerged as a promising drug delivery platform for targeted cancer therapy. Herein, we report the design and fabrication of a multi-functional photosensitizing nanogel system for photodynamic therapy (PDT) based on supramolecularly crosslinked biocompatible polymers. Nanogels were formed via host−guest interactions between β-cyclodextrin (β-CD)-conjugated polymers and a tetravalent adamantane-functionalized zinc phthalocyanine (Ada-TEG-ZnPc). Importantly, the Ada-TEG-ZnPc moiety functions as both a physical crosslinker and a photosensitizer, enabling the one-step assembly of photosensitizing nanogels. Post-assembly supramolecular functionalization with an adamantane-conjugated integrin-targeting peptide yielded cancer cell-targeting nanogels. It is demonstrated that both Ada-TEG-ZnPc and the resulting nanogels generated singlet oxygen efficiently upon light irradiation. In vitro studies using MDA-MB-231 breast cancer cells confirmed effective cellular internalization of both targeted and nontargeted nanogels, while enhanced uptake was observed for targeting peptide-functionalized systems. Reactive oxygen species generation within cells was confirmed, and pronounced phototoxicity was observed under light irradiation, with no dark toxicity. Overall, the targeted photodynamic nanogels exhibited high efficacy, highlighting the potential of supramolecular macromolecular design for targeted PDT applications.