Postoperative tumor suppression via ROS scavenging, VEGF capture, and photothermal therapy using a split aptamer-loaded hydrogel

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.