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Jianping Zhang

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Review Open access Sep 2026

Natural Product-Based Nanomedicine in the Treatment of Breast Cancer

Background: Breast cancer remains the most common malignant tumor among women worldwide. Although conventional treatments including surgery, chemotherapy, and radiotherapy are effective, they are confronted with challenges such as tumor heterogeneity, systemic toxicity, and recurrence driven by drug resistance. To overcome these limitations, natural products have emerged as promising therapeutic alternatives owing to their multi-target efficacy and favorable biocompatibility. However, their clinical translation is still hindered by poor chemical stability, low aqueous solubility, and inadequate bioavailability. Nanodelivery systems offer a transformative solution by enhancing bioavailability and enabling precision targeting through the enhanced permeation and retention effect, thereby widening the therapeutic window and minimizing off-target toxicity. Purpose: This review evaluates diverse nanoparticle-based delivery systems and their targeting mechanisms in natural product-based breast cancer therapy. By examining inherent advantages and translational challenges, this analysis provides critical insights into the clinical development and application of these nanoformulations. Methods: A systematic literature search was performed in PubMed, ScienceDirect, Springer, Taylor & Francis, and Web of Science to identify relevant studies on natural product-based nanoformulations for breast cancer therapy. Results: Natural products exert anti-breast cancer effects through mechanisms such as inducing apoptosis, arresting the cell cycle, inhibiting invasion and metastasis, suppressing angiogenesis, and regulating autophagy. To overcome clinical hurdles, three complementary targeting strategies have been developed: passive, active, and stimuli-responsive targeting. These advances are shifting nanomedicines toward active precision therapy, markedly improving the therapeutic index. With multiple formulations already approved or in clinical pipelines, this field is rapidly progressing from laboratory research to clinical implementation. Conclusions: Natural products possess potent anti-breast cancer effects, and the application of nanodelivery technology effectively overcomes their inherent limitations of poor stability and low bioavailability. Although preliminary findings are promising, large-scale, randomized controlled clinical trials are urgently needed to systematically evaluate their safety, efficacy, and practical potential for clinical translation in breast cancer management.

Kai-Yan Su, Yan Li, Dong-mei Zhang et al. · 0 citations
Review Open access Jul 2026

Targeting the CD47–SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next‐generation therapeutic strategies

Abstract Immune checkpoint inhibitors have transformed cancer therapy with the programmed cell death protein 1–programmed death‐ligand 1 axis, demonstrating substantial efficacy by targeting adaptive immunity across multiple malignancies. However, the limited clinical responses observed in a considerable proportion of patients highlights the need for more effective engagement of innate immune mechanisms. In this context, the cluster of differentiation 47–signal regulatory protein α (CD47–SIRPα) axis has emerged as a next‐generation immune checkpoint that regulates phagocytosis. CD47 is a ubiquitously expressed transmembrane glycoprotein containing an N‐terminal extracellular immunoglobulin variable‐like domain and is frequently overexpressed in both solid tumors and hematological malignancies. By binding to SIRPα on macrophages, CD47 transmits a canonical “don't eat me” signal that suppresses phagocytosis and enables tumor immune evasion. Beyond this canonical role, CD47 interacts with ligands such as thrombospondin‐1 and integrins to regulate tumor cell migration, metabolic adaptation, and immune balance within the tumor microenvironment. Importantly, CD47 links innate immune clearance with antigen presentation and downstream adaptive immune activation, positioning it as an actionable node for next‐generation therapeutic designs. Although the first‐generation CD47 blockade has revealed challenges related to hematologic toxicity, antigen sink effects, and limited monotherapy durability, these challenges have also accelerated the development of more selective, controllable, and context‐responsive therapeutic strategies. In this Review, we elucidate the structural features, molecular mechanisms, pathological functions, therapeutic strategies, translational challenges, and emerging solutions of CD47, with the aim of providing a theoretical basis for overcoming current therapeutic limitations and advancing more precise cancer immunomodulatory strategies.

Ruimei Zhou, LingJie Jing, Jianping Zhang et al. · 0 citations

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