Kim Seongmin, Lee Jihye, Byun Huiguk, Kim Jinseong, Kim Won Jong
Department of Chemistry, POSTECH-CATHOLIC Biomedical Engineering Institute, POSTECH, Pohang 37673, South Korea.
Medical Science and Engineering, School of Convergence Science and Technology, Pohang University of Science and Technology (POSTECH), Pohang 37673, South Korea.
J Control Release. 2025 Aug 10;384:113883. doi: 10.1016/j.jconrel.2025.113883. Epub 2025 May 23.
Surgical resection is the primary treatment for early-stage breast cancer. However, residual tumor cells often lead to postsurgery recurrence. Current adjuvant therapies focus on eliminating residual tumors but overlook the postsurgery tumor microenvironment (TME) on residual tumor growth, resulting in limited therapeutic efficacy. In particular, reactive oxygen species (ROS) generated during the surgical procedure induce vascular endothelial growth factor (VEGF) secretion, which promotes the growth of residual tumor cells. In this study, we developed Apt-Au@Gel, a multifunctional therapeutic platform combining ROS scavenging, VEGF capture, and photothermal therapy (PTT) to enhance postsurgery tumor suppression. Apt-Au@Gel consists of a cross-linked hydrogel composed of polymeric phenylboronic acid (pPBA) and polyvinyl alcohol (PVA), encapsulating VEGF split aptamer-functionalized gold nanoparticle (Apt-AuNPs). This platform dynamically scavenges ROS through boronic ester-based covalent interactions, while the released Apt-AuNPs aggregate through complementary sequence binding, and the VEGF split aptamer sequences combine to form the complete VEGF aptamer, enabling VEGF capture. The AuNPs aggregation enhances the photothermal conversion efficiency, allowing PTT upon near infrared (NIR) laser irradiation. In vitro and in vivo studies demonstrated the effective suppression of postsurgery tumor recurrence. These findings provide valuable insights into the synergistic effects of ROS scavenging, VEGF capture, and PTT, offering a promising strategy for postsurgery tumor therapy.
手术切除是早期乳腺癌的主要治疗方法。然而,残留的肿瘤细胞常常导致术后复发。目前的辅助治疗主要集中在消除残留肿瘤,但忽视了术后肿瘤微环境(TME)对残留肿瘤生长的影响,导致治疗效果有限。特别是,手术过程中产生的活性氧(ROS)诱导血管内皮生长因子(VEGF)分泌,促进残留肿瘤细胞的生长。在本研究中,我们开发了Apt-Au@Gel,这是一种多功能治疗平台,结合了ROS清除、VEGF捕获和光热疗法(PTT),以增强术后肿瘤抑制作用。Apt-Au@Gel由由聚合物苯硼酸(pPBA)和聚乙烯醇(PVA)组成的交联水凝胶构成,包裹着VEGF分裂适体功能化的金纳米颗粒(Apt-AuNPs)。该平台通过基于硼酸酯的共价相互作用动态清除ROS,而释放的Apt-AuNPs通过互补序列结合聚集,VEGF分裂适体序列结合形成完整的VEGF适体,实现VEGF捕获。AuNPs的聚集提高了光热转换效率,在近红外(NIR)激光照射下实现PTT。体外和体内研究证明了对术后肿瘤复发的有效抑制。这些发现为ROS清除、VEGF捕获和PTT的协同作用提供了有价值的见解,为术后肿瘤治疗提供了一种有前景的策略。