International Journal of Molecular and Cellular Medicine (IJMCM)
Cellular and Molecular Biology Research Center, Babol University of Medical Sciences
چهارشنبه 17 دی 1404
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Rostaminasab S, Memarkashani S, rahdari T, Asghari S M. Synergistic Efficacy of Dual-Target HSA-Based Delivery for HER and VEGFR Co-Blockade in Triple-Negative Breast Cancer. Int J Mol Cell Med 2025;
URL: http://ijmcmed.org/article-1-2652-fa.html
URL: http://ijmcmed.org/article-1-2652-fa.html
Synergistic Efficacy of Dual-Target HSA-Based Delivery for HER and VEGFR Co-Blockade in Triple-Negative Breast Cancer. مجله بین المللی سلولی و مولکولی. 1404;
: (34 مشاهده)
Resistance to monotherapies targeting receptor tyrosine kinases remains a major challenge in triple‑negative breast cancer (TNBC). Here, we developed a dual‑target HSA‑based nanobioconjugate combining human serum albumin (HSA)‑encapsulated Lapatinib—an EGFR1/2 inhibitor—with the VEGFR1/2‑blocking peptide VGB3 to achieve coordinated HER and VEGFR inhibition. Molecular docking predicted stable hydrogen‑bond and hydrophobic interactions between Lapatinib (free and HSA‑bound) and EGFR1/2, and between VGB3 and VEGFR1/2. HSA encapsulation enabled pH‑responsive, sustained drug release with faster kinetics under mildly acidic tumor conditions. Thermal denaturation assays confirmed increased conformational stability of HSA after binding, indicating structural integrity and biocompatibility. In vitro studies revealed that HSA‑Lapatinib exhibited a ~55 % reduction in IC₅₀ (from ≈ 71 µM to ≈ 32 µM) compared with free Lapatinib. The combination of 17 µM HSA‑Lapatinib and 0.18 µM VGB3 reduced cell viability to 25 % (CI = 0.29), confirming a strong synergistic effect. Flow‑cytometric analysis demonstrated a significant increase in apoptosis—from 40.8 % (HSA–Lapatinib) to 46.8 % (combination) (P < 0.05). RT‑PCR further showed a fourfold upregulation of VEGFR2 (P < 0.0001), supporting that HSA‑Lapatinib triggers compensatory VEGFR2 activation which is neutralized by VGB3. Collectively, these findings substantiate a mechanistic and quantitative synergy between HSA‑mediated HER inhibition and VGB3‑based VEGFR blockade. This dual‑target HSA‑Lapatinib/VGB3 system offers enhanced potency, reduced resistance, and a promising platform for precision‑guided TNBC therapy.
نوع مطالعه: Original Article |
موضوع مقاله:
Medical Pharmacology
دریافت: 1404/6/10 | پذیرش: 1404/9/16 | انتشار: 1404/5/6
دریافت: 1404/6/10 | پذیرش: 1404/9/16 | انتشار: 1404/5/6
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