Abstract

Abstract Photodynamic therapy (PDT) continues to encounter multifarious hurdles, stemming from the ineffectual preservation and delivery system of photosensitizers, the dearth of imaging navigation, and the antioxidant/hypoxic tumor microenvironment. Herein, a versatile cryomicroneedle patch (denoted as CMN‐CCPH) is developed for traceable PDT. The therapeutic efficacy is further amplified by catalase (CAT)‐induced oxygen (O 2 ) generation and Cu 2+ ‐mediated glutathione (GSH) depletion. The CMN‐CCPH is composed of cryomicroneedle (CMN) as the vehicle and CAT‐biomineralized copper phosphate nanoflowers (CCP NFs) loaded with hematoporphyrin monomethyl ether (HMME) as the payload. Importantly, the bioactive function of HMME and CAT can be optimally maintained under the protection of CCPH and CMN for a duration surpassing 60 days, leading to bolstered bioavailability and notable enhancements in PDT efficacy. The in vivo visualization of HMME and oxyhemoglobin saturation (sO 2 ) monitored by fluorescence (FL)/photoacoustic (PA) duplex real‐time imaging unveils the noteworthy implications of CMN‐delivered CCPH for intratumoral enrichment of HMME and O 2 with reduced systemic toxicity. This versatile CMN patch demonstrates distinct effectiveness in neoplasm elimination, underscoring its promising clinical prospects.