The most effective ways to treat cancer clinically are radiotherapy, chemotherapy, and surgery [1], [2]. Chemotherapy is a systemic treatment method that can make up for the ineffectiveness of the other two local therapies by utilizing chemotherapeutic medicines to mitigate cancer cells [3]. But chemotherapy still has certain drawbacks, such as, poor water solubility, hepatorenal toxicity, ineffective cell absorption, and non-specific drug delivery [1], [4]. This is because cancer cells uptake a small quantity of chemotherapeutic drugs, so it becomes necessary to administer these drugs multiple times, which usually results in developing drug resistance in the organism. Therefore, utilizing chemotherapy along with other alternative/ complimentary therapies can be one of the most efficient strategies to boost the efficacy of tumor treatment.

Nanoparticles can provide a method for allowing the photosensitizer (PS) to be accumulated specifically in cancer cells, owing to the tumor tissues' enhanced permeability and retention (EPR) effect [5]. Recently, silica-based nanoparticles have proven to be the potential candidates for the phototherapies. Numerous precursors and techniques are available for the synthesis of silica nanoparticles (SiNPs), providing versatility and further enabling the encapsulation of various drugs. SiNPs are commonly employed for applications in fields like bioimaging [6], biosensing [7], drug delivery [8], gene delivery [9], etc. Also, SiNPs have promising potential to be utilized as a drug delivery nanocarrier due to their large surface area, tailored shape and size, mono-dispersion, abundance of active hydroxyl groups on the surface, excellent biocompatibility, and inexpensive cost [10]. Another advantage of using SiNPs is their easy surface modification with particular biomolecules for tumor-cell targeting [11]. It has been shown in several reports that SiNPs are promising candidates for combined therapies [12], [13], [14].

In recent years, due to the simplicity, targeted and localized effects with low level of invasiveness, and minimal toxicity, phototherapy has gained attention as a potential method for treating cancer. Two conventional phototherapy methods are photodynamic therapy (PDT) and photothermal therapy (PTT), which work via absorption of light and PS in order to produce reactive oxygen species (ROS) and heat to mitigate cancerous cells, respectively [15], [16]. PTT is a technique for treating cancer cells that involves introducing various materials into the cells that have a high photothermal conversion efficiency. These materials then convert light into heat energy when exposed to an external light source, often visible or near infrared radiation (NIR), which might lead to the mitigation of cancerous cells [17], [12]. Numerous materials have been considered as a potential PTT candidate such as indocyanine green [12], cobalt ferrite, silver, and gold nanoparticles [18], [19], [20] but they all have few drawbacks, such as low absorptivity in visible or NIR region, photobleaching of the material, or limited photothermal conversion.

PDT is another photoinduced method utilized for treating various abnormalities, including cancer. PDT has become a viable alternative to chemo and radiation therapy [21], [22]. The basic principle behind PDT is that when administered systemically, light-sensitive species, or photosensitizers (PSs), can be preferentially localized in cancer cells [23]. When such PS are triggered by light of wavelength in the visible or NIR, they can transmit energy from their triplet excited state to nearby oxygen molecules. As a result, reactive oxygen species, consisting of OH., O2., etc. are formed. Several cellular components, such as mitochondria, plasma, nuclear, and lysosomal membranes, among others, are oxidized by ROS, which contribute to the apoptosis and necrosis-mediated death of cancer cells [11], [24]. The PDT efficacy can be linked to the amount of ROS generated, and the singlet oxygen is widely acknowledged as the primary cytotoxic species that kill cancer cells. Therefore, given the right circumstances, PDT provides the benefit of being a powerful and selective way to mitigate cancer cells without affecting nearby healthy cells.

Numerous disadvantages are also connected with the already reported PS in the literature. They tend to form self-aggregates in aqueous environments like blood, because they are mostly hydrophobic in nature or have low solubility in water. This changes their photophysical characteristics, specifically the reduction in their singlet oxygen producing ability. Additionally, PS must accumulate only in tumor cells in order to prevent the death of healthy cells. For eliminating such problems, PS are loaded in nanoparticles (Nps). In order to assure a highly successful method for mitigating malignant cells via a synergistic way, contemporary cancer treatment approaches thus utilize the logical combination of various techniques over single ones. According to several reports, combining chemotherapy with phototherapies (PTT and PDT) can improve effectiveness and restrict the development of drug resistance [12], [14], [18], [25].

The cationic phenothiazinium dye, thionine acetate has undergone extensive research due to its intriguing physicochemical characteristics. It is commonly employed as a PS in phototherapies, photogalvanic investigations, and as a photo-initiator for vinyl polymerization experiments [26]. The absorption maxima of this dye lies around 600 nm wavelength, which belongs to the phototherapeutic region (600–900 nm). It also generates high quantum yield of ROS and has decent aqueous solubility [27], [28]. Thionine is a common biological stain that is especially useful in histology owing to its strong affinity for biological membranes [27]. Being a part of the phenothiazinium family, it exhibits selectivity towards microbial and tumor cells. Cancer cells can exhibit photoinduced DNA damage, improper cell functioning, and possible genotoxic and cytotoxic activities in the presence of thionine, which is also beneficial in treating a variety of diseases [29].

DNA is an essential biomolecule which controls all chemical processes that occur inside the cells. The preservation of DNA's structural integrity is crucial for the cell to operate properly. Numerous anticancer agents primarily target DNA in order to produce damage or cause significant alterations in the native structure of the DNA molecule. This inhibits crucial biological processes including DNA transcription and replication, etc., and may eventually lead to cell death [30]. Furthermore, the interaction studies of drugs with serum proteins are also performed widely. The most prevalent proteins in the circulatory systems of different organisms are called serum albumins, and they manage a variety of physiological processes including pH buffering and regulating serum osmotic pressure, among others. Serum albumins are the promising candidates for selectively transporting therapeutic drugs to cellular targets because they have reversible binding interactions with various drugs [31].

The aim of our study was to optimize the physicochemical and photoinduced characteristics of TA by employing core shell SiNPs to develop a novel nanoformulation for multimodal therapies. We have investigated the efficacy of STA NPs for the PDT and PTT therapies. Additionally, the STA Nps' cytotoxicity was also determined by examining their binding interactions with calf thymus DNA (Ct-DNA). Furthermore, STA Nps' binding interactions with human serum albumin (HSA) were also carried out for analyzing the effect of drugs on its biophysical characteristics. The use of PS in cancer treatments needs to be greatly emphasized due to the diverse therapeutic properties offered by a single nanoformulation with multi-modal capabilities.