Cancer is a major public health issue worldwide. Despite the numerous treatment methods available, the demand for effective, safe, and highly efficient anti-tumor therapies remains urgent. Many natural drugs exhibit anti-tumor effects and have demonstrated excellent therapeutic potential in clinical treatments [1]. Curcumin, a natural polyphenol extracted from turmeric, has been reported to possess various pharmacological activities, including anti-oxidation, anti-inflammation, apoptosis induction and tumor angiogenesis inhibition [2,3]. Due to these effects, curcumin holds great promise as an anti-cancer agent. However, the poor aqueous solubility and low drug loading efficiency have limited the clinical application of curcumin [4]. Its insolubility makes it difficult to achieve effective therapeutic concentrations in tumor tissues through injection, and the low drug loading requires a high dose that may cause adverse side effects. Thus, developing a promising nanoparticle for curcumin loading via pharmaceutical approaches seems to be an inevitable path. Nanoparticle drug carriers have been extensively studied due to their precise drug delivery capabilities. Nanoparticles can solubilize and protect hydrophobic agents, increase their stability and circulation time, and enhance drug delivery to tumor tissues based on the enhanced permeability and retention (EPR) effect. Various nanoparticle formulations have been explored to address the limitations of curcumin, including liposomes [5,6], polymer nanoparticles [7], and exosomes [8], etc [9]. These formulations have achieved improved anti-cancer effects of curcumin in preclinical studies. However, traditional nanoparticle drug carriers often have a low drug loading and weak active targeting ability, which severely limits their clinical applications. To address these issues, here we constructed a novel self-assembled curcumin (Cur), which is mediated by fructose and self-assembled with curcumin as the main body [10]. To further enhance the stability and active targeting of Cur, polydopamine (PDA) was modified onto the surface of Cur (Cur-PDA) and macrophage membrane was utilized to coat the whole Cur-PDA (Cur-PDA@CM). PDA offers several advantageous properties for enhancing the efficacy of tumor targeting nano-formulations. These include high biocompatibility and adhesion, as well as multiple drug release-response mechanisms such as pH-sensitivity, GSH-sensitivity, thermal-sensitivity, and photothermal conversion ability [11]. PDA modification endowed the nanoparticles with enhanced stability and photothermal effects simultaneously. Macrophages are one of the professional phagocytes in the body, playing a crucial role in inflammation, immune responses and clearance towards abnormal substances and tumor cells [12]. Therefore, encapsulating nanoparticles with macrophage membranes make it possible to enhance active tumor targeting ability using this cell-cell adhesion and potentially exert an immunoregulatory effect on the tumor microenvironment (TME). The encapsulation strategy we chose can achieve effective tumor targeting, reducing the non-specific distribution of nanoparticles in the body and potential side effects [13].

Through this innovative design, the nanoparticles we prepared can not only take advantage of the anti-tumor effects of curcumin, but also utilize the photothermal therapy effects of PDA, promoting the production of ROS to further kill tumor cells, also promote tumor-associated macrophages (TAMs) to polarize towards anti-tumor M1 phenotype. We hope that this innovative treatment strategy will provide an effective new path for cancer treatment.

This study aimed to comprehensively evaluate the Cur-PDA@CM system in terms of photothermal conversion, cancer cell targeting, anti-cancer efficacy through in vitro cellular experiments and in vivo live animal imaging. These results would provide preclinical evidence supporting the clinical translation and application of this novel nanoparticle formulation. The research outcomes may provide new insights into designing nanoparticle platforms that can fully harness the anti-cancer potential of natural products. The schematic is illustrated in Fig. 1.