Multi-functionalization, a promising adaptation to overcome challenges to clinical translation of nanomedicines as nano-diagnostics and nano-therapeu-tics for breast cancer

Background: Breast cancer (BC) is one of the most aggressive and prevalent types of cancer, which is associated with a high rate of mortality and colossal potential of metastasis to other body organs. Convention-ally, there are three commonly employed strategies for the treatment of BC including, surgery, radiations and chemotherapy; however, these modalities are associated with several deleterious effects and a high rate of re-lapse. Objective: This review was aimed to critically discuss and conceptualize existing evidences related to the pharmaceutical significance and therapeutic feasibility of multi-functionalization of nanomedicines for early diagnosis and efficient treatment of BC. Results: Though the implication of nanotechnology-based modalities has revolutionised the outcomes of diagnosis and treatment of BC; however, the clinical translation of these nanomedicines is facing grandeur chal-lenges. These challenges include recognition by the reticuloendothelial system (RES), short plasma half-life, non-specific accumulation in the non-cancerous cells, and expulsion of the drug(s) by the efflux pump. To cir-cumvent these challenges, various adaptations such as PEGylation, conjugation of targeting ligand(s), and site-responsive behaviour (i.e., pH-responsiveness, biochemical, or thermal-responsiveness) have been adapted. Similarly, multi-functionalization of nanomedicines has emerged as an exceptional strategy to improve the phar-macokinetic profile, specific targetability to the tumor microenvironment (active targeting) and efficient inter-nalization, and to alleviate the expulsion of internalized drug contents by silencing-off efflux pump. Conclusion: Critical analysis of the available evidences revealed that multi-functionalization of nanomedicines is a plausible and sustainable adaptation for early diagnosis and treatment of BC with better therapeutic out-comes.