Increasing evidence shows that the extracellular matrix (ECM) is an important regulator of breast cancer (BC). The ECM comprises of highly variable and dynamic components. Compared with normal breast tissue under homeostasis, the ECM undergoes many changes in composition and organization during BC progression. Induced ECM proteins, including fibrinogen, fibronectin, hyaluronic acid, and matricellular proteins, have been identified as important components of BC metastatic cells in recent years. These proteins play major roles in BC progression, invasion, and metastasis. Importantly, several specific ECM molecules, receptors, and remodeling enzymes are involved in promoting resistance to therapeutic intervention. Additional analysis of these ECM proteins and their downstream signaling pathways may reveal promising therapeutic targets against BC. These potential drug targets may be combined with new nanoparticle technologies. This review summarizes recent advances in functional nanoparticles that target the ECM to treat BC. Accurate nanomaterials may offer a new approach to BC treatment.

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Growth differentiation factor-8 (GDF-8) is a member of the transforming growth factor-beta superfamily. Studies in vitro and in vivo have shown GDF-8 to be involved in the physiology and pathology of ovarian reproductive functions. In vitro experiments using a granulosa-cell model have demonstrated steroidogenesis, gonadotrophin responsiveness, glucose metabolism, cell proliferation as well as expression of lysyl oxidase and pentraxin 3 to be regulated by GDF-8 via the mothers against decapentaplegic homolog signaling pathway. Clinical data have shown that GDF-8 is expressed widely in the human ovary and has high expression in serum of obese women with polycystic ovary syndrome. GDF-8 expression in serum changes dynamically in patients undergoing controlled ovarian hyperstimulation. GDF-8 expression in serum and follicular fluid is correlated with the ovarian response and pregnancy outcome during in vitro fertilization. Blocking the GDF-8 signaling pathway is a potential therapeutic for ovarian hyperstimulation syndrome and ovulation disorders in polycystic ovary syndrome. GDF-8 has a regulatory role and potential importance in ovarian reproductive activity and may be involved in folliculogenesis, ovulation, and early embryo implantation.

Preterm birth (PTB) remains a leading cause of infant mortality and morbidity, significantly affecting the long-term health, welfare, and development of newborns. Tocolytics, such as ritodrine, a β₂-adrenergic receptor agonist, are widely used in developing countries due to their affordability for preventing PTB by inhibiting uterine contractions. However, ritodrine's short half-life necessitates frequent administration, and prolonged high-dose usage often leads to serious maternal side effects, prompting discontinuation. The uterine first-pass effect, where vaginally administered drugs preferentially target the uterus, can enhance drug concentration in uterine tissue while minimizing systemic absorption and side effects. This study designed a kind of ritodrine-loaded thermosensitive gel (Gel@Rit) to intervene in PTB by exploiting the uterine first-pass effect and investigate its underlying mechanisms. The gel, formulated with poloxamer, demonstrated excellent temperature sensitivity and viscosity, ensuring sustained ritodrine release in vitro. Plasma pharmacokinetic and tissue distribution studies in pregnant mice confirmed the uterine first-pass effect, showing significantly higher drug concentrations in the uterus and markedly lower plasma levels following Gel@Rit administration. The distinctive drug-time curve in Gel@Rit-treated mice, along with uterine tissue fluorescence profiles, elucidated four mechanisms of uterine localization: diffusion through reproductive tract cavities, penetration via vaginal and uterine structures, diffusion through systemic circulation, and retrograde transvaginal veno-uterine artery exchange. This study provides valuable insights into vaginal drug delivery research methodologies, advancing therapeutic strategies for uterine-related conditions and benefiting clinical outcomes in PTB prevention.