Photoactivatable nanogenerators of reactive species for cancer therapy

Abstract

In recent years, reactive species-based cancer therapies have attracted tremendous attention due to their simplicity, controllability, and effectiveness. Herein, we overviewed the state-of-art advance for photo-controlled generation of highly reactive radical species with nanomaterials for cancer therapy. First, we summarized the most widely explored reactive species, such as singlet oxygen, superoxide radical anion (O₂ ^●-), nitric oxide (^●NO), carbon monoxide, alkyl radicals, and their corresponding secondary reactive species generated by interaction with other biological molecules. Then, we discussed the generating mechanisms of these highly reactive species stimulated by light irradiation, followed by their anticancer effect, and the synergetic principles with other therapeutic modalities. This review might unveil the advantages of reactive species-based therapeutic methodology and encourage the pre-clinical exploration of reactive species-mediated cancer treatments.

Keywords: Alkyl radicals; Carbon monoxide; Phototherapy; Reactive nitrogen species; Reactive oxygen species.

Graphical abstract

Scheme 1

Schematic illustration of the photoactivatable nanogenerators of reactive species including reactive oxygen, reactive nitrogen, and reactive carbon species for cancer therapy.

Fig. 1

The mechanisms of type-I and type-II PDT of cancer (R represents the substrate participating in the type-I photochemical reactions, ISC: intersystem crossing).

Fig. 2

(a) A schematic diagram of preparing supramolecular metallo-nanodrugs by the coordination of peptide, PSs, and Zn²⁺. Reprinted with permission [91]. Copyright 2018, American Chemical Society. (b) The transformation of peptide-porphyrin nanoparticles to peptide-porphyrin nanofibers activated by acid and the PDT application after intravenous injection. Reprinted with permission [92]. Copyright 2020, Wiley-VCH. (c) The formation of FHP photoactive nanostructure for NIRF imaging-guided PDT. Reprinted with permission [93]. Copyright 2020, Wiley-VCH. (d) The molecule structure of RDM-BDP for mitochondria targeting PDT. Reprinted with permission [94]. Copyright 2018, American Chemical Society.

Fig. 3

(a) Synthetic procedure of Hf-DBP NMOF and the ¹O₂ generation under light illumination. Reprinted with permission [98]. Copyright 2014, American Chemical Society. (b) The structure of DBC-UiO and the photosensitization under light irradiation. Reprinted with permission [99]. Copyright 2015, American Chemical Society. (c) The formation schematic of UNM. Reprinted with permission [102]. Copyright 2017, American Chemical Society. (d) Structure schematic of HUC-PEG. Reprinted with permission [103]. Copyright 2020, Elsevier. (e) A schematic diagram of preparing TPE-PHO nanostructure and the substitution activated phototherapy mechanism. Reprinted with permission [101]. Copyright 2020, American Chemical Society.

Fig. 4

(a) A schematic diagram of the oxygen self-supplying UMOFs@Au NPs for enhanced PDT efficacy in vivo. Reprinted with permission [104]. Copyright 2020, American Chemical Society. (b) The preparation process of holey Pd NSs (H–Pd NSs). Reprinted with permission [105]. Copyright 2020, American Chemical Society. (c) The detection of the decomposition process of H₂O₂ into O₂ by electron spin resonance spectra. Reprinted with permission [105]. Copyright 2020, American Chemical Society. (d) Viability of 4T1 cells treated with different conditions. Reprinted with permission [105]. Copyright 2020, American Chemical Society.

Fig. 5

(a) The preparation of OPNi and (b) the mechanism of OPNi induced synergistic phototherapy. Reprinted with permission [106]. Copyright 2019, Wiley-VCH. (c) The preparation of SPNs photoactive nanomaterials for combined PDT/chemotherapy application. Reprinted with permission [107]. Copyright 2019, Wiley-VCH. (d) The release mechanism of IPM-Br for chemotherapy.

Fig. 6

(a) Molecular structure of PcA. (b) Molecular structure of the Ir(III)–COUPY conjugate. (c) The molecule structure of L-3C for constructing COF-808. (d) The molecule structure of L-3N for constructing COF-909. (e) Molecular structure of ENBS-B. (f) Molecular structure of cationic superoxide radical anion generator-ENBOS. (g) Molecular structure of SORgenTAM.

Fig. 7

(a) Schematic structure of Ti-TBP NMOF enabling both types I and type II PDT. Reprinted with permission [113]. Copyright 2019, American Chemical Society. (b) Coordinated complexation of bacteriochlorin ligands and Zr⁴⁺ to obtain Zr-TBB NMOF for type I and type II PDT. Reprinted with permission [98]. Copyright 2020, American Chemical Society. (c) The mechanism schematic of porphyrin-based 2D CON for PTT and type I PDT. Reprinted with permission [114]. Copyright 2019, American Chemical Society.

Fig. 8

(a) The structure schematic of the photoactive Pt(IV) prodrug. Reprinted with permission [128]. Copyright 2018, Royal Society of Chemistry. (b) Schematic illustration of the IPH-NO for enhanced antitumor therapy. Reprinted with permission [130]. Copyright 2019, Royal Society of Chemistry. (c) The release mechanism of UCNPs(DOX)@CS-RBS nanomaterials activated by light illumination and the acid. Reprinted with permission [131]. Copyright 2017, Royal Society of Chemistry.

Fig. 9

(a) Schematic illustration of DPP-NF NPs for multifunctional cancer therapy. Reprinted with permission [122]. Copyright 2018, Royal Society of Chemistry. (b) The release mechanism of ^●NO from DPP-NF NPs. Reprinted with permission [122]. Copyright 2018, Royal Society of Chemistry. (c) The preparation of Ag₂S@BSA-SNO for cancer therapy. Reprinted with permission [129]. Copyright 2020, Springer Nature. (d) The preparation process of m-PB-NO for antitumor therapy. Reprinted with permission [127]. Copyright 2019, Elsevier. (e) PA imaging-guided ^●NO/photothermal combination therapy. Reprinted with permission [132]. Copyright 2019, Elsevier. (f) Molecule structure of photoNOD and rNOD. (g) PA imaging of photoNOD-1 and release of ^●NO.

Fig. 10

(a) The antitumor mechanism of Fe(CO)₅@Au under laser irradiation. Reprinted with permission [138]. Copyright 2020, American Chemical Society. (b) The photoreduction mechanism of PPOSD and the chemotherapeutic effect of DOX. Reprinted with permission [139]. Copyright 2019, American Chemical Society. (c) The synthetic procedure of MCM@PEG–CO–DOX for antitumor therapy. Reprinted with permission [140]. Copyright 2019, Elsevier. (d) Synthetic schematic of PPPPB-CO-TPZ NPs for antitumor therapy upon laser irradiation. Reprinted with permission [137]. Copyright 2019, Elsevier.

Fig. 11

(a) The reaction mechanism of photo-triggered generation of alkyl radical species. Reproduced with permission [6]. Copyright 2017, Wiley-VCH. (b) The synthetic procedure of Fe₅C₂-BSA-AIPH/PCM for imaging-guided cancer treatment. Reprinted with permission [145]. Copyright 2018, American Chemical Society. (c) Schematic illustration of CuFeSe₂-based multifunctional nanomaterials for oxygen-independent synergistic therapy of cancer. Reprinted with permission [146]. Copyright 2019, American Chemical Society. (d) The formulation of TPP-NN NPs and the mechanism of 638 nm laser-triggered generation of alkyl radical species for antitumor therapy. Reprinted with permission [148]. Copyright 2019, American Chemical Society.