As the fourth highest lethal cancer, colorectal cancer (CRC) has become one of the most challenging diseases. The incidence of CRC is still rising continually and becoming prevalent among young people. [1] Originating from a polyp of the inner wall of colorectal epithelium, colorectal cancer invades the muscles and nearby lymph nodes, followed by spreading to other organs. [2] Traditional treatments, including chemotherapy, surgery, and radio therapy, still lack a complete cure for CRC due to the existence of recurrence, metastasis, and drug resistance, [3,4] which is associated with cancer stem cells (CSCs). [5] Surgery is the most common treatment of early stage colorectal cancer. But most of the colorectal cancer patients are diagnosed in the advanced stage. [6,7] Chemotherapy is a current strategy for patients in advanced stage, which is facing weak treatment effectiveness and side effects. The systematic side effects further limit the administration dose of chemo-drugs. [[8], [9], [10], [11], [12]] Accordingly, it is urgent to develop novel alternative methods to treat colorectal cancer.

Photodynamic therapy (PDT) is a developing anticancer strategy, during which photosensitizers (PSs) are inactive in dark and can be activated by light with specific wavelength to generate reactive oxygen species (ROS). As a promising anticancer treatment, PDT possesses the merits of noninvasiveness, spatial specificity, and minimal systematic side effects. [[13], [14], [15], [16]] Profiting from these advantages, PDT has emerged as a promising strategy for the treatment of serval located cancers, including skin, esophagus, lung and bladder cancers, [[17], [18], [19], [20], [21]] and was approved for clinical using. [22,23] Due to their salient and tunable photophysical characteristics, Ru(II)-polypyridyl complexes have been widely studied for their applications in anticancer. [[24], [25], [26], [27], [28], [29]] The success of TLD1433 [30] has been spurring the researchers to explore the potential of Ru(II) based PSs. As a kind of coordination complexes, the diversification of ligands provides the opportunities to adjust the photophysical performance as well as the bio-function to carry out novel Ru(II) based PSs. [[31], [32], [33], [34], [35]] Schiff bases are always used as metal ions chelating ligands and so that form coordination complexes with different physical and chemical properties. Complexes carrying Schiff base ligands have been extensively studied in anticancer, anti-inflammatory, and antibacterial activities. [26,29]

Cancer stem cells (CSCs) is a kind of subpopulation of cancer cells with the ability of self-renewal, differentiation, and tumorigenicity, which is associated with the recurrence, metastasis, and drug resistance of cancer. [[36], [37], [38]] Inhibition towards CSCs could effectively improve anticancer outcome. Resveratrol (Fig. 1), a food natural product found in grape leaves and skins, [[39], [40], [41], [42]] was reported to possess cancer stem cell inhibitory capacity through varies pathways. [[43], [44], [45], [46], [47]] Seung Ho Baek reported that the resveratrol can inhibit the phosphorylation of STAT3 without influence on its prototype and so that suppress serval stemness related proteins. [47] But the in vitro anticancer activity of resveratrol is lack of potency. [48,49] One of the resveratrol derivatives, compound amino-Res (Fig. 1) was proved to potently inhibit cancer cells with nanomole-classed IC50 values. [50] In this study, we introduced the resveratrol derivative compound amino-Res to the Schiff base ligand to form a series of novel Ru(II) based PSs (Fig. 1) with the expectation to enhance the anticancer efficiency.