Photothermal agents can harvest light energy and convert it into heat, offering a targeted and remote-controlled way to destroy carcinomatous cells and tissues. Inspired by the biological organization of polypeptides and porphyrins in living systems, here we have developed a supramolecular strategy to fabricate photothermal nanodots through peptide-modulated self-assembly of photoactive porphyrins. The self-assembling nature of porphyrins induces the formation of J-aggregates as substructures of the nanodots, and thus enables the fabrication of nanodots with totally inhibited fluorescence emission and singlet oxygen production, leading to a high light-to-heat conversion efficiency of the nanodots. The peptide moieties not only provide aqueous stability for the nanodots through hydrophilic interactions, but also provide a spatial barrier between porphyrin groups to inhibit the further growth of nanodots through the strong π-stacking interactions. Thermographic imaging reveals that the conversion of light to heat based on the nanodots is efficient in vitro and in vivo, enabling the nanodots to be applied for photothermal acoustic imaging and antitumor therapy. Antitumor therapy results show that these nanodots are highly biocompatible photothermal agents for tumor ablation, demonstrating the feasibility of using bioinspired nanostructures of self-assembling biomaterials for biomedical photoactive applications.

Tremendous interest in self-assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self-assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self-assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self-assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non-covalent interactions, strategies, and the nanoarchitectures of self-assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in-depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self-assembly in improving the efficiency of photodynamic and photothermal therapy.

Supramolecular photosensitizer nanodrugs that combine the flexibility of supramolecular self-assembly and the advantage of spatiotemporal, controlled drug delivery are promising for dedicated, precise, noninvasive tumor therapy. However, integrating robust blood circulation and targeted burst release in a single photosensitizer nanodrug platform that can simultaneously improve the therapeutic performance and reduce side effects is challenging. Herein, we demonstrate a multicomponent coordination self-assembly strategy that is versatile and potent for the development of photodynamic nanodrugs. Inspired by the multicomponent self-organization of polypeptides, pigments, and metal ions in metalloproteins, smart metallo-nanodrugs are constructed based on the combination and cooperation of multiple coordination, hydrophobic, and electrostatic noncovalent interactions among short peptides, photosensitizers, and metal ions. The resulting metallo-nanodrugs have uniform sizes, well-defined nanosphere structures, and high loading capacities. Most importantly, multicomponent assembled nanodrugs have robust colloidal stability and ultrasensitive responses to pH and redox stimuli. These properties prolong blood circulation, increase tumor accumulation, and enhance the photodynamic tumor therapeutic efficacy. This study offers a new strategy to harness robust, smart metallo-nanodrugs with integrated flexibility and multifunction to enhance tumor-specific delivery and therapeutic effects, highlighting opportunities to develop next-generation, smart photosensitizing nanomedicines.