Hydrophilic Biocompatible Fluorescent Organic Nanoparticles as Nanocarriers for Biosourced Photosensitizers for Photodynamic Therapy

Abstract

Most photosensitizers of interest for photodynamic therapy—especially porphyrinoids and chlorins—are hydrophobic. To circumvent this difficulty, the use of nanocarriers is an attractive strategy. In this perspective, we have developed highly water-soluble and biocompatible fluorescent organic nanoparticles (FONPs) made from citric acid and diethyltriamine which are then activated by ethlynene diamine as nanoplatforms for efficient photosensitizers (PSs). Purpurin 18 (Pp18) was selected as a biosourced chlorin photosensitizer combining the efficient single oxygen generation ability and suitable absorption in the biological spectral window. The simple reaction of activated FONPs with Pp18, which contains a reactive anhydride ring, yielded nanoparticles containing both Pp18 and Cp6 derivatives. These functionalized nanoparticles combine solubility in water, high singlet oxygen generation quantum yield in aqueous media (0.72) and absorption both in the near UV region (FONPS) and in the visible region (Soret band approximately 420 nm as well as Q bands at 500 nm, 560 nm, 660 nm and 710 nm). The functionalized nanoparticles retain the blue fluorescence of FONPs when excited in the near UV region but also show deep-red or NIR fluorescence when excited in the visible absorption bands of the PSs (typically at 520 nm, 660 nm or 710 nm). Moreover, these nanoparticles behave as efficient photosensitizers inducing colorectal cancer cell (HCT116 and HT-29 cell lines) death upon illumination at 650 nm. Half maximal inhibitory concentration (IC50) values down to, respectively, 0.04 and 0.13 nmol/mL were observed showing the potential of FONPs[Cp6] for the PDT treatment of cancer. In conclusion, we have shown that these novel biocompatible nanoparticles, which can be elaborated from biosourced components, both show deep-red emission upon excitation in the red region and are able to produce singlet oxygen with high efficiency in aqueous environments. Moreover, they show high PDT efficiency on colorectal cancer cells upon excitation in the deep red region. As such, these functional organic nanoparticles hold promise both for PDT treatment and theranostics.