Engineering dual-targeted lipid nanocarriers for precision delivery of quercetin in breast cancer therapy: a comprehensive review.

Abstract

A significantly higher mortality rate in breast cancer than in lung cancer worldwide raises serious concerns despite advances in biomarker research and diagnosis. Conventional chemotherapeutics are usually associated with poor tumor selectivity, multi-drug resistance, adverse effects due to the conventional route of administration and high doses, and systemic toxicity, which restricts the therapeutic outcome in breast cancer management. Several phytocompounds have recently been investigated for potential anticancer activity, and some bioactive molecules have also entered into clinical trials. Quercetin, a naturally derived flavonoid, has drawn significant attention due to its modulation of multiple molecular pathways involved in cell proliferation, apoptosis, angiogenesis, oxidative stress, inflammation, and metastasis in breast cancer. However, its poor pharmacokinetic properties lead to limited oral bioavailability in medical applications. Thus, this review article summarizes recent advancements in quercetin-loaded lipid-based nanotherapeutics for breast cancer targeting. This extensive manuscript summarizes the phytochemistry and derivatives of quercetin, along with the demand for lipid-based delivery approaches compared to other nanotherapeutics. Recent advances in quercetin-loaded nanosuspensions, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, hybrid nanoparticles, etc., are discussed, focusing on the physicochemical, pharmacokinetic properties, and molecular targeting capabilities. Furthermore, the review highlights preclinical evidence demonstrating enhanced cytotoxicity, improved bioavailability, increased apoptosis, metastasis, and reduced systemic toxicity compared with free quercetin. A few clinical translation approaches, along with the persistent challenges, are also discussed in this article. The overall understanding of this "single-platted" article further showcases an unexplored dimension to advance the knowledge of quercetin-based lipid nanoformulations for breast cancer therapy.

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