Biomimetic Nanotheranostics Camouflaged with Cancer Cell Membranes Integrating Persistent Oxygen Supply and Homotypic Targeting for Hypoxic Tumor Elimination

Treatment resistance of the tumors to photodynamic therapy (PDT) owing to O₂ deficiency largely compromised the therapeutic efficacy, which could be addressed via modulating oxygen levels by using O₂ self-enriched nanosystems. Here, we report on augmenting the O₂-evolving strategy based on a biomimetic, catalytic nanovehicle (named as N/P@MCC), constructed by the catalase-immobilized hollow mesoporous nanospheres by enveloping a cancer cell membrane (CCM), which acts as an efficient nanocontainer to accommodate nitrogen-doped graphene quantum dots (N-GQDs) and protoporphyrin IX (PpIX). Inheriting the virtues of biomimetic CCM cloaking, the CCM-derived shell conferred N/P@MCC nanovehicles with highly specific self-recognition and homotypic targeting toward cancerous cells, ensuring tumor-specific accumulation and superior circulation durations. N-GQDs, for the first time, have been evidenced as a new dual-functional nanoagents with PTT and PDT capacities, enabling the generation of ¹O₂ for PDT and inducing local low-temperature hyperthermia for thermally ablating cancer cells and infrared thermal imaging (IRT). Leveraging the intrinsic catalytic features of catalase, such N/P@MCC nanovehicles effectively scavenged the excessive H₂O₂ to sustainably evolve oxygen for a synchronous O₂ self-supply and hypoxia alleviation, with an additional benefit because the resulting O₂ bubbles could function as an echo amplifier, leading to the sufficient echogenic reflectivity for ultrasound imaging. Concurrently, the elevated O₂ reacted with N-GQDs and PpIX to elicit a maximally increased ¹O₂ output for augmented PDT. Significantly, the ultrasound imaging coupled with fluorescence imaging, IRT, performs a tumor-modulated trimodal bioimaging effect. Overall, this offers a paradigm to rationally explore O₂ self-supply strategies focused on versatile nanotheranostics for hypoxic tumor elimination.