## 1 Introduction  
Cancer is endangering millions of lives and has been predicted to diagnose an estimated 1.5 million new cases [1]. Among many types of cancer, the therapeutic success of Triple-negative breast cancer (TNBC) is not satisfactory. The conventional therapeutic strategies for TNBC are DNA intercalating taxanes, platinum compounds, and tyrosine, and serine-threonine kinase inhibitors, such as Everolimus, Cetuximab. However, in the clinic, treatment with these drugs produces drug resistance to TNBC patients. Thus, it is essential to improve not only diagnostic tools for early detection of the tumor but also to develop selective ligands for therapy with very few adverse events in healthy tissues. Nanomedicine, especially the development of drug delivery systems that accumulate in the tumor actively as well as passively with the advantage of multi-targetability and show promise as conventional cancer therapy, is necessary. It is known that most of the current drug delivery systems are failing in clinical trials because of the lack of specific targetability, poor tumor penetration, tumor heterogeneity, and complex association of tumor-associated immune cells and stroma. Consequently, targeted drug delivery systems that utilize diverse ligands to understand unique biomarkers that are present on tumor cell components have turned out to be extremely critical in selective transport of medication and improving therapeutic efficacy. Targeted cancer remedy techniques are expected to differentiate between healthy and most cancer tissues. For this, the ligands might be decorated on the surface of the drug-carrier structures that use a reagent-free organic synthesis method for enhancing early prognosis and subsequent remedy in tumors. Our research presented in this study is linked to the concept of personalized medicine, that also has the convenience of designing the delivery system-drug combination on a need to need basis by utilizing targeting ligands-carrier combination using a synthesis approach that minimizes reagents like the copper-free cyclic Alkyne-Azide click reaction that doesn't require any dangerous chemical substances, reagents, or any unique reaction conditions. The unique understanding accrued by this approach will provide a concept of development in drug delivery with the skills of rational designing of targeting ligand custom-designed drug carriers to address specific functions within the tumor microenvironment. Further, nanoparticles are the drug delivery systems of choice for targeted delivery of anticancer drugs [2,3] in the pharmaceutical industry. Nanoparticles improve the delivery of hydrophobic drugs, lower their metabolic degradation in the eliminating organs, target their delivery to cancer cells directly by logical surface modifications on the delivery systems, and show controlled or extended or sustained drug delivery [4, 5, 6]. Besides having the capability to improve the solubility of hydrophobic drugs, nano-delivery systems can additionally target cancerous cells with the aid of two distinctive strategies: passive and active targeting. The functions of the passive targeting delivery systems depend on the ability of nano-delivery systems to exploit the Enhanced Permeability and Retention (EPR) effect [7,8]. As a result, the nano-molecules can extravasate and accumulate at the tumor site. However, not all tumors manifest the EPR effect, and even if they do, the angiogenesis is not uniform through the depths of the tumor resulting in unequal medication at different sites of cancer. Further, the EPR effect may not be as effective in some tumors as in the others [9,10]. Thus, developing targeted delivery systems taken up by active targeting via receptors on the tumor cells is the need of the hour. This research uses albumin as carrier and acetazolamide as the ligand to target carbonic anhydrase (CA) receptor overexpressed in cancer cells in hypoxic conditions. Albumin is the most abundant plasma protein in the human body.