Self‐Supplying O₂ through the Catalase‐Like Activity of Gold Nanoclusters for Photodynamic Therapy against Hypoxic Cancer Cells

Abstract

Photodynamic therapy (PDT) typically involves oxygen (O ) consumption and therefore suffers from greatly limited anticancer therapeutic efficacy in tumor hypoxia. Here, it is reported for the first time that amine-terminated, PAMAM dendrimer-encapsulated gold nanoclusters (AuNCs-NH ) can produce O for PDT via their intrinsic catalase-like activity. The AuNCs-NH not only show optimum H O consumption via the catalase-like activity over the physiological pH range (i.e., pH 4.8-7.4), but also extend such activity to acidic conditions. The possible mechanism is deduced from that the enriched tertiary amines of dendrimers are easily protonated in acidic solutions to facilitate the preadsorption of OH on the metal surface, thereby favorably triggering the catalase-like reaction. By taking advantage of the exciting feature on AuNCs-NH , the possibility to supply O via the catalase-like activity of AuNCs-NH for PDT against hypoxia of cancer cells was further studied. This proof-of-concept study provides a simple way to combine current O -dependent cancer therapy of PDT to overcome cancer cell hypoxia, thus achieving more effective anticancer treatments.

Innovative Strategies for Hypoxic‐Tumor Photodynamic Therapy

“…[47,48] In addition to catalase,s everal other nanomaterials,s uch as MnO 2 nanoparticles,g old nanoclusters,p latinum nanozymes,a nd mesoporous cerium oxide hollow nanoparticles, have been used in PDT-related systems to catalyze the transformation of H 2 O 2 to O 2 . [49][50][51][52][53][54][55] Fore xample,L in et al recently fabricated ac atalase-like nanocomposite containing MnO 2 and chlorin e6 by using human serum albumin as the building block. [52] After reduction of KMnO 4 to form MnO 2 in ah uman serum albumin-containings olution, chlorin e6 is covalently linked with lysine residues in the protein, which then self-assembles in aqueous solution to generate spherical particles with diameters of about 120 nm (polydispersity index, about 0.1;z eta potential, about À25 mV).…”

A Semiconducting Polymer Nano‐prodrug for Hypoxia‐Activated Photodynamic Cancer Therapy

“…[3] As ak ey component for PDT,p hotosensitizers have been continuously optimized for improved therapeutic efficacies. In addition to small-molecule dyes,m any inorganic and organic nanomaterials have been exploited as photosensitizers,w hich include metallic nanoparticles, [4] gold nanoclusters, [5] quantum dots, [6] two-dimensional materials, [7] upconverting nanoparticles, [8] and organic porphysomes. [9] Despite the promise of PDT in cancer therapy,its oxygen reliance limits the therapeutic effect against tumor hypoxia.…”

Therapeutic Nanoreactors as In Vivo Nanoplatforms for Cancer Therapy

“…[22] Recently,s uch at reatment strategy was explored by many studies for theranostic applications by means of photodynamic therapy (PDT), irradiation therapy, and so on, to synergistically ande fficiently treat cancerc ells with minimized adverse side effects. [19,23] As another treatment option, it has been well documented that many tumor tissues often suffer from the inadequacy of one or more amino acids ynthesis routes, which drives them to solely depend on extracellular supply of the amino acids for survival and to satisfy protein biosynthesis demands. [24] In this context, the application of specific enzymest od egrade some of non-essential or semi-essential amino acids that are beneficial to tumor cells growth has been proposed as ap romising approacht oinhibit and kill auxotrophic cancer cells.…”