A Two-Stage Nanoengineered Microneedle Platform for On-Demand Tumor-Microenvironment-Responsive Therapy and Enhanced Wound Healing Against Postoperative Breast Cancer Recurrence

Postoperative metastatic recurrence and wound infection pose significant threats to survival after breast cancer surgery. To address these challenges, an ideal therapeutic strategy should incorporate minimally invasive multifunctional biomaterials capable of simultaneously preventing tumor recurrence and promoting wound healing. Herein, we report a novel two-stage microneedle (MN) platform engineered via the integration of nanotechnology and tumor-microenvironment-responsive design. This system is fabricated using a stepwise casting strategy and features tip-to-base architecture equipped with on-demand smart nanocarriers for synergistic therapy against postoperative breast cancer recurrence and wound complications. The MN consists of a photo-crosslinked hydrogel tip encapsulating chitosan-based self-assembled nanocarriers and a gelatin–polydopamine hydrogel backing layer. Owing to its hierarchical structural design, the MN exhibits excellent mechanical strength with a compression force of up to 4.48 N per needle, sufficient for efficient skin penetration. Moreover, the platform demonstrates sustained pH-responsive behavior and specific tumor microenvironment targeting, enabling controlled drug release. The MN also displays outstanding biocompatibility and multi-functional therapeutic properties, including antibacterial adhesion, self-healing capability, swelling performance, and biodegradability, greatly broadening its potential as a precision medicine tool. Both in vitro and in vivo studies validated the robust and integrated therapeutic efficacy of the MN system in suppressing metastatic breast cancer recurrence and enhancing infected wound healing. This work provides a significant advance in the design of smart two-stage MNs with comprehensive functionality for minimally invasive adjuvant therapy after breast cancer surgery.