Traceable Lactate-Fueled Self-Acting Photodynamic Therapy against Triple-Negative Breast Cancer.

The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC), while the overproduction of lactate (LA) facilitates the development, aggressiveness, and therapy resistance of TNBC. To address these issues, a self-acting PDT nanosystem (HL@hMnO-LOx@HA) is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha (HPPH), luminol, and LA oxidase (LOx) in a hyaluronic acid (HA)-coated hollow manganese dioxide (hMnO) nanoparticle. LOx catalyzes the oxidation of LA into pyruvate and hydrogen peroxide (HO), thus depleting the overproduced intratumoral LA. In the acidic tumor microenvironment, HO reacts with luminol and hMnO to yield blue luminescence as well as O and Mn, respectively. Mn could further enhance this chemiluminescence. HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT. The generated O alleviates the hypoxia state of the TNBC tumor to produce sufficient O for self-oxygenation PDT. The Mn performs magnetic resonance imaging to trace the self-acting PDT process. This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.