Breast cancer chemotherapy is often hindered by systemic toxicity, limited tumor selectivity, and suboptimal drug accumulation at the target site. To overcome these challenges, this proposal introduces a novel hypoxia-responsive hydrogen-bonded organic framework (HOF) as a multifunctional nanocarrier for targeted anticancer drug delivery. The HOF is designed to provide high drug-loading capacity, structural biocompatibility, and controlled degradation within the tumor microenvironment, enabling efficient and site-specific drug release while minimizing premature leakage.

To enhance therapeutic performance, the HOF will be coated with a hybrid membrane derived from platelet and breast cancer cells, creating a biomimetic camouflage capable of prolonging circulation time, evading immune recognition, and promoting homotypic tumor targeting. Furthermore, the system will be functionalized with a cancer-targeting aptamer that selectively recognizes receptors overexpressed on breast cancer cells, thereby improving cellular uptake and treatment specificity.

The resulting nanoplatform is expected to exhibit favorable physicochemical characteristics, including nanoscale particle size, high encapsulation efficiency, colloidal stability, and preserved membrane-associated functionality. The combination of a stimuli-responsive HOF structure, dual-membrane cloaking, and aptamer-mediated active targeting represents an integrated therapeutic strategy not commonly achieved in previously reported HOF-based drug delivery systems.

Comprehensive in vitro studies will investigate drug-release behavior under tumor-relevant conditions, serum stability, cellular internalization, selective cytotoxicity, and apoptosis induction in cancerous and non-cancerous cells. The stability and functionality of the targeting moieties will also be assessed. In vivo evaluation in a murine breast cancer model will examine biodistribution, tumor growth inhibition, systemic safety, histopathological changes, and overall therapeutic efficacy.

The developed platform will be characterized using advanced structural, morphological, thermal, and spectroscopic techniques. Overall, this study seeks to establish a next-generation HOF-based nanomedicine capable of enhancing therapeutic precision, reducing off-target effects, and improving the translational potential of breast cancer chemotherapy.