Breast cancer ranks as a leading killer globally with high incidence rates and huge healthcare burden. While chemotherapy remains a mainstay in breast cancer management, the adverse effects to healthy tissues, drug resistance and cancer relapse further exacerbate the therapeutic landscape, presenting a dire need for efficient delivery vehicles. This research work presents the synthesis of inorganic calcium carbonate nanocrystals and their physiochemical characterization including assessment of morphology, functional group and thermal decomposition via transmission electron microscopy, Fourier transform infrared spectroscopy and thermogravimetry respectively. Through stoichiometric optimization, nano-sized vectors of calcium carbonate at approximately 200 nm with −9 mV zeta potential were fabricated and evaluated for their biocompatibility. Interestingly, the nanocarriers exhibited remarkable encapsulation efficiency of doxorubicin and enhanced cellular internalization. Furthermore, the in vitro release kinetics study elucidated pH-responsiveness, with a cumulative drug release of 90.1 % in acidic milieus. The drug release pattern from DOX-loaded CaCO3 nanocarriers was fitted to the release kinetics mathematical models, portraying non-Fickian mechanism with a combination of diffusion and dissolution from pH-triggered release. The DOX-bound nanocomplexes also demonstrated significant antiproliferative effects in breast cancer cells, while the blank nanocarriers showed no innate cytotoxicity. Protein corona profiling of the nanocarriers further revealed the prominent adsorption of dysopsonin transport proteins which aid in extending circulation period for improved biodistribution. Overall, the research findings suggest the potential of calcium carbonate nano-vehicles as strategic nanoplatforms for effective doxorubicin delivery in breast cancer cells.