A Janus polydopamine nanomotor hydrogel enables enhanced tumor penetration and potent synergistic photothermal-photodynamic therapy

Hydrogels are widely recognized as promising carriers for antitumor drug delivery owing to their tunable physicochemical properties. However, elevated interstitial fluid pressure and a dense extracellular matrix within tumors often restrict efficient drug penetration. Herein, we developed a nanomotor-based injectable hydrogel (CPPZ@R837) that integrates Janus-type polydopamine nanobowls (PDA NBs) functionalized with platinum nanoparticles (Pt NPs) as catalytic propellants and zinc phthalocyanine (ZnPc) as a photosensitizer to construct PPZ nanomotors (NMs). These PPZ NMs, together with the immunoadjuvant imiquimod (R837), were embedded into a chitosan (CTS)-based thermosensitive hydrogel through Michael addition and Schiff base reactions. Upon laser irradiation, the hydrogel underwent a sol-gel phase transition, enabling the controlled release of PPZ NMs and R837. The Pt NPs catalyzed the decomposition of tumor-overexpressed hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ), which not only provided propulsion for the NMs but also alleviated tumor hypoxia, thereby enhancing the efficacy of photodynamic therapy (PDT). This multifunctional system markedly improved intratumoral drug penetration and exhibited potent antitumor performance, achieving significant tumor growth inhibition (83.7%) and effective suppression of metastasis. Collectively, these findings highlight the great potential of this nanomotor-based hydrogel as an advanced platform for synergistic cancer therapy. • Injectable CTS hydrogel integrates catalytic Janus PPZ nanomotors and R837. • Laser activation triggers sol-gel switching for precise NM release control. • Pt-driven H 2 O 2 decomposition supplies O 2 for NM propulsion and hypoxia relief. • Active nanomotion markedly enhances intratumoral penetration efficiency. • CPPZ@R837 achieves potent inhibition of tumor growth and metastasis.