Perfluoroalkylated amphiphilic porphyrin nanomicelles for improved photodynamic therapy: anti-tumour efficacy through stability enhancement and O2 enrichment

Abstract

Amphiphilic porphyrin nanomicelles have been established as new single-molecule photodynamic agents (PDAs) for cancer treatment. Further improvement of the photodynamic performance will increase the potential of this class of PDAs for practical application. Here, we prepare four new porphyrin compounds F-TSCnP (n = 5–8) that bear a n-C₅F₁₁, n-C₆F₁₃, n-C₇F₁₅, and n-C₈F₁₇ chain, respectively. We demonstrate that, compared with the analogues that bear a shorter perfluoroalkyl or n-C₈H₁₇ chain, n-C₈F₁₇-bearing compound F-TSC8P can self-assemble into nanomicelles that possess increased stability and uniformity as well as improved intracellular self-delivering capacity. We further illustrate that nanomicelles formed by F-TSC8P form a unique fluorocarbon microphase, which can enrich and deliver O₂ to achieve remarkably enhanced photosensitizing activity for ¹O₂ generation. In vivo assay using a mouse model reveals that, compared with the fluorine-free counterpart, F-TSC8P, which has a therapeutic index of 10, exhibits a 150% increase in photodynamic activity for tumour growth inhibition.