Nanotechnology has turn out to be one of the most imperative study endeavors of the early 21st century, as scientists are creating nanoscale assemblages by employing the unique properties of matter at atomic and molecular scale. (McNeil, 2005). Nanotechnology created a variety of materials at the nanoscale level. Nanoparticles are particulate combinations with a minimum diameter of 100 nanometers that belong to an immense range of materials (Khan et al., 2019). Although the definition defines nanoparticles with dimensions less than 0.1m or 100nm, in the field of drug delivery, larger nanoparticles (size > 100nm) are preferred for loading a sufficient amount of drug onto nanoparticles (De Jong & Borm, 2008).
Cancer is notorious for being one of the major cause of death throughout the world, thus better treatment strategies are desperately needed (Duraidi & Tsibizova, 2021). Finding novel and innovative cancer treatments is a huge challenge all around the world (Siegel & Miller, 2020). Despite the fact that various ways have been established to reduce mortality, chronic pain, and improve quality of life, there is still a gap in the adequacy of cancer medicines (Jin et al., 2020). The therapeutic efficacy of various malignant tumors has substantially improved as the variety of approaches for treating cancer has increased, as has the concept of a tailored treatment (Zitvogel et al., 2008). Women are suffering most frequently by breast cancer, accounting for 22.9 percent of all cancers in females. Chemotherapy is an important treatment option for breast cancer patients. Traditional chemotherapeutic drugs, on the other hand, are commonly linked to side effects and eventually lose their effectiveness when tumor drug resistance develops (Liu et al., 2022).
Nanoparticles have the potential to increase the safety and efficacy of encapsulated medications by improving their stability and solubility, promoting transport across membranes, and extending circulation periods (Mitchell et al., 2021). Many advantages of nanoparticle (np)-based drug delivery systems in cancer treatment have been demonstrated, including good pharmacokinetics, specific targeting of tumor cells, reduced side effects, and drug resistance (Yao et al., 2020). Traditional chemotherapy medicines and nucleic acids are among the drugs found on the inside of the nano-carriers, indicating that they could be used for both cytotoxic and gene therapy (Y. Chen et al., 2014). Additionally, for some poorly soluble medications, nanoparticles provide a substrate for encapsulating and distributing the pharmaceuticals into circulation.
Nano-carriers can increase the half-life of medications and induce their accumulation within tumor tissues due to the size and surface properties of nanoparticles, as well as their function of boosting permeability and retention (Meng et al., 2016). Because of their ability to target and multifunctionality, nanoparticles have considerable advantages in cancer therapy (Xie et al., 2010). Nanoparticles can be used to not only image tumor tissues, but also to determine the stage of cancer and therapy response (Toy et al., 2014). Furthermore, nanoparticles can carry a therapeutic agent to the tumor site and deliver the needed therapeutic agent concentrations via molecular and environmental stimuli (Swierczewska et al., 2016).
There have been numerous types of nano drug delivery systems considered thus far, mostly organic and some inorganic (Y. Li et al., 2010). Calcium carbonate (CaCO3) is an inorganic substance with excellent biodegradability, biocompatibility, and simplicity of modification, making it an ideal smart carrier for anticancer drug delivery (Qi et al., 2014). CaCO3 nanoparticles have been employed in a lot of studies to control drug release and maintain pharmaceuticals for a long period due to their lengthy biodegradation time (Lee et al., 2012). Furthermore, in aqueous settings, CaCO3 nanoparticles do not swell or change permeability (Maleki Dizaj et al., 2015).
Another important aspect of CaCO3 nanoparticles is their ability to be functionalized with targeted agents. CaCO3 particles are a good drug delivery carrier because they degrade slowly and are biocompatible thus not toxic to the body (Chandler et al., 2020). Calcium carbonate nanoparticles prepared by bottom-up method have improve their solubility (Hassim & Rachmawati, 2010). The citrate technique can be used to manufacture CaCO3 nanoparticles, followed by the synthesis of calcium monoxide (CaO) and calcium hydro-oxide Ca(OH)2 nanoparticles (Ghiasi & Malekzadeh, 2012). Calcium carbonate nanoparticles prepared by cockle shell have good biocompatibility for anti-carcinogenic medications (Islam et al., 2012).
Nanostructured calcium carbonate can be used to deliver genes and medicines for cancer therapy employing a CaCO3 co-precipitation approach for co-delivery of genes and medicines (S. Chen and colleagues, 2012). A pH-sensitive calcium carbonate aragonite nanocrystal can be used as a novel anticancer delivery mechanism (Shafiu Kamba et al., 2013a). The nanocrystals of calcium carbonate synthesized by spray drying method can be used as vehicles for drug delivery (Vergaro et al., 2015). Calcium carbonate nanoparticles induced cancer cell reprogramming to inhibit tumor development and invasion in an organ-on-a-chip system in 2021. The calcium carbonate nanoparticles appeared to limit the aggressiveness of tumor cells without affecting the growth and behavior of stromal cells, according to the findings (Lam et al., 2021). Calcium carbonate nanoparticles were discovered to activate tumour metabolic reprogramming and modify tumour metastasis (Som et al., 2019). Calcium carbonate nanoparticles, in erythrocytes to enable efficient elimination of extracellular lead ion (Ru et al., 2019).
Vitamin D3 (cholecalciferol) is a fat soluble vitamin that is produced by the body from a precursor, 7-dehydrocholesterol and metabolized by the liver and kidney. (Plum & Deluca, 2010). Vitamin D is known to be necessary for calcium and phosphate ion absorption in the small intestine, mobilization from bone tissue, and desorption in the kidney (Bouillon et al., 2008). Vitamin D appears to be involved in the regulation of other critical biological processes such as cell proliferation and differentiation, according to new data (Giammanco et al., 2015). When active, it not only regulates calcium metabolism, but also triggers a slew of biological responses that affect cellular development, proliferation, apoptosis, and immune system function (Chakraborti, 2011). Several meta-analyses have looked into the link between circulating vitamin D levels in the body besides the risk of cancer, with resourceful analyses being able to compile larger datasets than individual research (Xiong & Surgery, 2018). Vitamin D has been linked to a variety of malignancies, the most common being colon, breast, and prostate cancers, according to epidemiological research (Jacobs et al., 2016). The deficiency of vitamin D has been interconnected to the beginning, development, and prognosis of breast cancer in a number of preclinical as well as clinical investigations (Ismail et al., 2018). The 1-hydroxylase enzyme is found in various extra renal body tissues together with the soft tissues of breast, and is required for the conversion of inactive 25(OH)D to the metabolically active form, 1,25(OH)2D. The circulating amount of 25(OH) D give the impression to be the most important element in determining the active form of vitamin D's production in different tissues. The 1,25(OH)2D generated locally binds to the vitamin D receptors (VDRs) located on the epithelium cells of breast and regulates expression of several genes. Epithelial cells of breast correspondingly contain the enzyme 24-hydroxylase (CYP24) which converts the active form of vitamin D [1,25(OH)2D] to lesser active metabolic forms including [24,25(OH)2 D] and [1,24,25-(OH)3 D]. For therapeutic uses, vitamin D3 nano- and microencapsulation has received little attention. Cholecalciferol microencapsulation has been studied as a pharmacological model or as a nutrient supplement in some studies. For oral administration, vitamin D (cholecalciferol) was encapsulated in the hydrophobic alginate nanoparticles. However, no reports of calcitriol or other active equivalents being nanoencapsulated for cancer treatment have been reported to our knowledge (Almouazen et al., 2013).
PLGA (Poly lactic-co-glycolic acid) nanoparticles can act as a manifesto for vitamin D based treatment for pancreatic and lung cancer (Ramalho et al., 2015). Nanoparticle-based vitamin D formulations in modifying vitamin D levels in patients with proven vitamin D insufficiency improved vitamin D level (Manek, 2017). Biosynthesis of CaCO3 nanoparticles, synthesized from the leach solution and the aqueous extract of the plant Myrtus communis plant as an environmental friendly approach (Uzunolu & zer, 2018). Vitamin D conjugated gold nanoparticles can be employed as functional carriers to increase osteogenic differentiation of human adipose-derived stem cells (Nah et al., 2019). Polypeptide nanoparticle mineralized with calcium, and used it as drug delivery vehicle for the treatment of osteosarcoma (K. Li et al., 2020). Vitamin D3 plus paclitaxel (PTX) loaded, poly lactic glycolic acid (PLGA) nanoparticles have shown inhibitory effect on MCF-7 (breast cancer) cell line (Khodaverdi et al., 2020). Cholecalciferol (Vitamin D3) repressed cell growth and encouraged apoptosis in the CaSki (Cervical cancer) cell line (Bhoora et al., 2020). Enteric coated hydroxyapatite nanoparticle developed for oral delivery of a vitamin D3 formulation with modulated release (Dissanayake et al., 2021).
This study aims to produce Vitamin D conjugated Calcium carbonate nanoparticles and evaluate their anticancer activity on breast cancer cell line (MCF-7).