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.

Photodynamic therapy (PDT) is a clinically approved, non-invasive therapy currently used for several solid tumors, triggering cell death through the generation of reactive oxygen species (ROS). However, the hydrophobic nature of most of the photosensitizers used, such as chlorins, limits the overall effectiveness of PDT. To address this limitation, the use of nanocarriers seems to be a powerful approach. From this perspective, we have recently developed water-soluble and biocompatible, fluorescent, organic nanoparticles (FONPs) functionalized with purpurin-18 and its derivative, chlorin p6 (Cp6), as new PDT agents. In this study, we aimed to investigate the induced cell death mechanism mediated by these functionalized nanoparticles after PDT photoactivation. Our results show strong phototoxic effects of the FONPs[Cp6], mediated by intracellular ROS generation, and subcellular localization in HCT116 and HT-29 human colorectal cancer (CRC) cells. Additionally, we proved that, post-PDT, the FONPs[Cp6] induce apoptosis via the intrinsic mitochondrial pathway, as shown by the significant upregulation of the Bax/Bcl-2 ratio, the activation of caspases 9, 3, and 7, leading poly-ADP-ribose polymerase (PARP-1) cleavage, and DNA fragmentation. Our work demonstrates the photodynamic activity of these nanoparticles, making them promising candidates for the PDT treatment of CRC.

Starting from purpurin-18, a stable purpurin-18 imide derivative with intensive absorption in the near infrared has been synthesized. The opening of the exocycle anhydride by a primary alkylamine bearing an adamantyl group, allows after cyclization the formation of an imide function. This reaction led to the purpurinimide adamantane derivative (PIA) which enables the inclusion of a photosensitizer in the cavity of cationic cyclodextrin coupled to cellulose nanocrystals (CNCs/β-CD ⁺ ). Preliminary in vitro results showed that CNCs/β-CD ⁺ complexes improved internalization of photosensitizers into HCT116 and HT-29 colorectal cancer cell lines. Moreover, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay of CNCs/β-CD ⁺ /PIA complexes showed significant dose-dependent phototoxicity after illumination with red light, with IC ₅₀ values of 2.5 and 8.7 nM, for HT 116 and HT-29, respectively, and very low dark toxicity. The current results suggest that these nanoparticle/photosensitizer complexes are promising and useful tools for photodynamic therapy (PDT).

Background/Objectives: To address current aggressive breast cancer challenges, a novel series of eight N-chalconyl imidazolidone derivatives (N-CIMZs 1–8) was synthesized and evaluated for direct cytotoxicity and immunomodulation via macrophage polarization. Methods: Following antiproliferative screening against four representative breast cancer lines, the prototype candidate N-CIMZ 1 was selected for cell cycle and scratch-wound healing assays in MCF-7 cells. Multi-parametric flow cytometry on human THP-1 macrophages tracked cellular stress (γH2AX), metabolic markers (iNOS), and surface dynamics (LAP (TGF-β1), CD163, CD206, CD209). Results: N-CIMZ 1 acted as an antimitotic agent, inducing G2/M phase arrest (51.0%) and restricting MCF-7 wound confluence to 33% at 24 h. In THP-1 macrophages, it maintained low induction of γH2AX-mediated DNA damage signaling. Under alternative M2 pressure, N-CIMZ 1 intercepted polarization by forcing high membrane retention of the immunosuppressive peptide LAP (81%) and suppressing the scavenger marker CD163 (12%) while buffering hyper-reactive CD206+/CD209+ hybrid spikes down to 2.33% under M1 stress. Conclusions: N-CIMZ 1 represents a promising multi-modal scaffold combining antimitotic and macrophage-modulating properties. This targeted immunomodulation effectively subverts tumor-supportive macrophage phenotypes, showcasing the potential of microenvironment reprogramming to counter breast cancer progression and metastasis.

Le cancer colorectal (CCR) est l'une des tumeurs malignes les plus diagnostiquées au monde, et les modalités thérapeutiques conventionnelles actuelles sont souvent invasives, résistantes et induisent des effets secondaires toxiques sur les tissus sains. C’est pourquoi de nouvelles approches thérapeutiques ciblées se développent. Dans cette optique, on trouve la thérapie photodynamique (PDT) qui présente plusieurs avantages évidents par rapport aux modalités classiques, telles qu'une invasivité minimale, une grande sélectivité vis-à-vis des tissus cancéreux et moins d'effets secondaires. La PDT est une alternative thérapeutique approuvée cliniquement et actuellement utilisée pour plusieurs tumeurs solides, déclenchant la mort cellulaire par la génération d'espèces réactives de l'oxygène(ERO). Cependant, la nature hydrophobe de la plupart des photosensibilisateurs (PS) utilisés, tels que les chlorines, limite l'efficacité globale de la PDT. Pour surmonter cette limitation, l'utilisation de nanovecteurs semble être une approche puissante. Dans cette perspective, nous avons récemment développé des nanoparticules organiques fluorescentes (FONP) solubles dans l'eau et biocompatibles, fonctionnalisées avec de la purpurine-18 (Pp-18) et son dérivé, la chlorine p6 (Cp6), en tant que nouveaux agents de PDT. L’objectif de cette étude a été de déterminer in vitro le potentiel phototoxiquedes FONPs[Cp6] dans le traitement des modèles cellulaires 2D et 3D de lignées du CCR. Nos résultats montrent des effets phototoxiques importants des FONPs[Cp6], médiés par la génération des ERO intracellulaires dans les cellules de CCR HCT116 et HT-29. En outre après la PDT, nous avons prouvé que les FONP[Cp6] induisent l'apoptose par la voie mitochondriale intrinsèque, mais également l’autophagie. Notre travail démontre l'activité photodynamique de ces nanoparticules, ce qui en fait des candidats prometteurs pour le traitement du CCR.