Cascaded Amplifier Nanoreactor for Efficient Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) utilizes reactive oxygen species (ROS) to treat established diseases and has attracted growing attention in the field of cancer therapy. However, in a tumor microenvironment (TME), the inherent hypoxia and high level of antioxidants severely hamper the efficacy of ROS generation. Here, we describe a cascaded amplifier nanoreactor based on selfassembled nanofusiforms for persistent oxygenation to amplify ROS levels. The nanofusiform assembly is capable of photothermal and photodynamic treatment and regulation of redox oxidation stress by antioxidant depletion to prevent ROS tolerance. The Pt nanozyme decoration of the nanofusiform enables efficient oxygen supplements via Pt nanozyme-catalyzed decomposition of H 2 O 2 overexpressed in TME and generation of O 2 . Furthermore, the temperature elevation resulted from the photothermal effect of the nanofusiform increases the catalase-like catalytic activity of the Pt nanozyme for boosted oxygen generation. Thus, such a triple cascade strategy using nanozyme-based nanofusiforms amplifies the ROS level by continuous oxygenation, enhancing the efficacy of PDT in vitro and in vivo. Meanwhile, an in vivo multi-modal imaging including near-infrared fluorescence imaging, photothermal imaging, and magnetic resonance imaging achieves precise tumor diagnosis. The rationally designed nanofusiform acts as an efficient ROS amplifier through multidimension strengthening of continuous oxygenation, providing a potential smart nanodrug for cancer therapy.

Platinum nanoplatforms: classic catalysts claiming a prominent role in cancer therapy

“…In Pt nanoplatforms, there is a clear correlation between their structural features and their catalytic response towards O 2 generation. Thus, supported ultra-small (<2.5, 6,82 3.0, 7,89 3.5 nm 80,83 ), and small (16 nm 90 ) Pt NPs or Pt-nanodendrites 81,91 efficiently produced O 2 from H 2 O 2 . A two-step reaction mechanism for this process was proposed by Serra-Maia et al 5 (Fig.…”

“…7,83,89 In addition, these NPs can establish synergies with other moieties added to their surfaces. Thus, small Pt NPs have been combined with photosensitizers such as porphyrins, 7,14,82,89 indocyanine green, 6 chlorine e6 (Ce6) 90,95 which consume as-generated O 2 under irradiation with a suitable source yielding ROS and enhancing PDT in spite of tumoral hypoxia (Fig. 3A-right and Table 1).…”

“…Nevertheless, in the past few years, a range of novel therapies such as Photodynamic Therapy (PDT), Photothermal Therapy (PTT) and ChemoDynamic Therapy (CDT) have boosted the interest on Pt NPs given their ability to work as catalysts, photothermal agents, or radiotherapy sensitizers in single or combined therapies. 4–22…”

Recent Advances in Strategies for Addressing Hypoxia in Tumor Photodynamic Therapy

“…Recently, the employment of metal-based materials to promote the decomposition of tumor endogenous H 2 O 2 to generate oxygen has attracted increasing attention. Titanium dioxide-modified palladium (Pd) nanosheets [ 123 ], Pd nanoparticles [ 124 ], defective cobalt (Co) hydroxide [ 125 ], Co 3 O 4 nanoparticles [ 126 ], iridium (Ir) oxide [ 127 , 128 ], cerium (Ce) oxide nanoparticles [ 129 , 130 ], platinum (Pt) nanozyme [ 131 , 132 ], gold (Au) nanoclusters [ 133 ], iron (Fe)-based materials [ 134 , 135 , 136 , 137 , 138 ], etc. have been used to accelerate the decomposition of H 2 O 2 to generate oxygen.…”

Keratin-Based Nanoparticles with Tumor-Targeting and Cascade Catalytic Capabilities for the Combinational Oxidation Phototherapy of Breast Cancer

“…Photodynamic therapy (PDT), − a minimally invasive cancer treatment strategy with low systemic toxicity, employs a photosensitizer with low-intensity light of a specific wavelength to generate reactive oxygen species (ROS), mainly singlet oxygen ( 1 O 2 ), − which can interact with cells, causing them to undergo apoptosis and tissue destruction through a sequence of chemical and biological processes . However, glutathione (GSH), a strong antioxidant that protects cells from ROS damage, is present in 10–100-fold higher amounts in cancer cells than in cells of normal tissues .…”