As a cancer treatment, photodynamic therapy (PDT) uses photosensitizers to absorb light and produce reactive oxygen species (ROS) so as to induce cell death [1]. Among various photosensitizers, curcumin (CUR) is a natural compound found in turmeric and has shown potential as a PDT agent due to its low toxicity and high biocompatibility [2,3]. However, CUR has poor water dispersibility, low absorption and high degradability, leading to its low bioavailability [[4], [5], [6]]. In vitro cell experiments, CUR exhibits low cellular uptake efficiency, and previous reports have shown that significant cell-killing effects require a relatively long incubation time (24 h, 48 h) [7,8]. Additionally, CUR has a peak absorption wavelength of around 430 nm with poor absorption capacity at longer wavelengths. The limited penetration depth of short-wavelength light in clinical settings restricts the treatment depth. These issues hinder the clinical application of CUR-based PDT.

To address these problems, researchers have explored CUR modification as a means to enhance the efficacy of PDT. Banerjee et al. [9] modified the CUR structure with metal complexes, thus enhancing its stability in biological media and its phototoxicity in cells while selectively delivering CUR to cancer cells, thereby improving its bioavailability. Jefferson et al. [10] encapsulated CUR using polylactic acid and sulfated glucan via nanoprecipitation to enhance its water dispersibility and reduce the required amount of dimethyl sulfoxide (DMSO) for CUR dissolution, thereby reducing cell toxicity. Jalde et al. [11] combined CUR with chlorin e6 as a photosensitizer, demonstrating increased ROS production and excellent photodynamic efficacy against AsPC-1 cells (human metastatic pancreatic adenocarcinoma cells).

Titanium dioxide nanoparticles (TiO2 NPs) have been used as an effective nanocarrier platform for numerous photosensitizers due to their unique optical and photocatalytic properties [[12], [13], [14]]. TiO2 can also act as a photosensitizer itself, but only when exposed to UV light [15,16].And it has been reported that TiO2 NPs accumulate in tumor tissues through the enhanced permeability and retention effect (EPR) [17,18]. Moreover, the cationic polymer called Sofast is a cell transfection reagent which is positively charged [[19], [20], [21], [22]]. Therefore, it can bind to the surface of negatively charged particles and then enhance their stability and dispersion in aqueous solutions. Owing to its low cytotoxicity and fast cellular uptake efficiency, Sofast is believed to have the potential to improve cellular uptake and stability of nanoparticles. Most cancer cells possess a negatively charged surface [23], thus indicating that the use of Sofast as a coating material holds promise for enhancing its affinity with the cell membrane.

Here, we propose a novel nanodrug platform strategy that combines CUR with TiO2 nanoparticles and cationic polymer Sofast in order to enhance drug loading efficiency and improve photodynamic efficacy, as illustrated in Fig. 1. We describe the preparation process of this new composite nanoparticle, characterize its ROS production, and evaluate its cellular phototoxicity. We investigate the impact of this composite on cellular metabolism during cancer cell cytotoxicity and discuss the mechanisms underlying enhanced photodynamic efficacy and the potential prospects of this approach.