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

Background Breast cancer (BC) is one of the most aggressive and prevalent types of cancer which is associated with high rate of mortality and colossal potential of metastasis to other body organs. Conventionally, there are three commonly employed strategies for treatment of BC including, surgery, radiations and chemotherapy; however, these modalities are associated with several deleterious effects and high rate of relapse. Objective This review was aimed to critically discuss and conceptualize existing evidences related to 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 challenges. These challenges include, recognition by reticuloendothelial system (RES), short plasma half-life, non-specific accumulation in the non-cancerous cells, and expulsion of drug(s) by the efflux pump. To circumvent 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 been emerged as an exceptional strategy to improve pharmacokinetic profile, specific targetability to tumor microenvironment (active targeting) and efficient internalization, 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 outcomes.