Issue 37, 2021

Reactive oxygen species-responsive polydopamine nanoparticles for targeted and synergistic chemo and photodynamic anticancer therapy

Abstract

A thioketal-linked dimer of 3,4-dihydroxy-L-phenylalanine was prepared which underwent self-polymerisation in the presence of doxorubicin (Dox) in an ethanol/water (1 : 4, v/v) mixture with ammonia. The resulting Dox-encapsulated polydopamine (PDA) nanoparticles were further conjugated with molecules of a zinc(II) phthalocyanine (Pc)-based photosensitiser and a peptide containing the heptapeptide QRHKPRE sequence (labelled as QRH) that can target the epidermal growth factor receptor (EGFR) overexpressed in cancer cells. Upon internalisation into these cells through receptor-mediated endocytosis, these nanoparticles labelled as PDA-Dox-Pc-QRH were disassembled gradually via cleavage of the thioketal linkages by the intrinsic intracellular reactive oxygen species (ROS). The stacked Pc molecules were then disaggregated, resulting in activation of their photosensitising property upon irradiation. The ROS generated by the activated Pc promoted further degradation of the nanoparticles and release of Dox, thereby enhancing cell death by synergistic chemo and photodynamic therapy. Systemic injection of PDA-Dox-Pc-QRH into EGFR-overexpressed tumour-bearing nude mice led to targeted delivery to the tumour, and subsequent light irradiation caused complete tumour ablation without inducing notable toxicity.

Graphical abstract: Reactive oxygen species-responsive polydopamine nanoparticles for targeted and synergistic chemo and photodynamic anticancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
02 iyl 2021
Accepted
07 sen 2021
First published
09 sen 2021

Nanoscale, 2021,13, 15899-15915

Reactive oxygen species-responsive polydopamine nanoparticles for targeted and synergistic chemo and photodynamic anticancer therapy

G. Dai, J. C. H. Chu, C. K. W. Chan, C. H. J. Choi and D. K. P. Ng, Nanoscale, 2021, 13, 15899 DOI: 10.1039/D1NR04278E

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