Biodegradable Calcium Phosphate Nanotheranostics with Tumor‐Specific Activatable Cascade Catalytic Reactions‐Augmented Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is exploited as a promising strategy for cancer treatment. However, the hypoxic solid tumor and the lack of tumor-specific photosensitizer administration hinder the further application of oxygen (O 2)-dependent PDT. In this study, a biodegradable and O 2 self-supplying nanoplatform for tumor microenvironment (TME)-specific activatable cascade catalytic reactions-augmented PDT is reported. The nanoplatform (named GMCD) is constructed by coloading catalase (CAT) and sinoporphyrin sodium (DVDMS) in the manganese (Mn)-doped calcium phosphate mineralized glucose oxidase (GOx) nanoparticles. The GMCD can effectively accumulate in tumor sites to achieve an "off to on" fluorescence transduction and a TME-activatable magnetic resonance imaging. After internalization into cancer cells, the endogenous hydrogen peroxide (H 2 O 2) can be catalyzed to generate O 2 by CAT, which not only promotes GOx catalytic reaction to consume more intratumoral glucose, but also alleviates tumor hypoxia and enhances the production of cytotoxic singlet oxygen from light-triggered DVDMS. Moreover, the H 2 O 2 generated by GOx-catalysis can be converted into highly toxic hydroxyl radicals by Mn 2+-mediated Fenton-like reaction, further amplifying the oxidative damage of cancer cells. As a result, GMCD displays superior therapeutic effects on 4T1-tumor bearing mice by a long term cascade catalytic reactions augmented PDT.

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer

“…Furthermore, O 2 generation overcomes tumor hypoxia and improves PDT induced generation of 1 O 2 . These NPs showed selective accumulation at tumor sites monitored by FLI as well as Mn +2 mediated MRI 65 . In another study, Jiang et al, reported biocompatible polymeric NPs, pluronic F127 encapsulated hexyloxyethyl-devinyl pyropheophorbide-a (HPPH) and camptothecin (chemotherapeutic drug), whereby the NPs are selectively activated by ROS at the tumor site.…”

Advanced Cancer Starvation Therapy by Simultaneous Deprivation of Lactate and Glucose Using a MOF Nanoplatform

“…[ 3 ] Therefore, many efforts have been made to improve the efficacy of GOx‐mediated starvation efficacy. For example, catalysts such as MnO 2 [ 4 ] and catalase [ 5 ] were used to convert H 2 O 2 to H 2 O and O 2 to improve the local oxygen pressure, which could subsequently promote the catalytic activity of GOx. Unfortunately, for this strategy, the improved oxygen pressure was at the price of sacrificing the toxic H 2 O 2 , which will make the treatment less effective.…”

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem

“…On the one hand, ultrasound (US) exposure is devoted to clinical diagnostic imaging; on the other hand, acoustic luminescence from the US-mediated cavitation effect activates sonosensitizers to generate ROS, thus inducing cell apoptosis/necrosis caused by DNA fragmentation, cytoskeletal shrinkage and chromatin condensation 27 , 28 . In addition, a high level of ROS depletes the antioxidant GSH, causing lipid peroxidation and leading to the initiation of ferroptosis 29 , 30 . Among various types of organic and inorganic sonosensitizers, IR780, a lipophilic heptamethine dye with a peak optical absorption at 780 nm, is considerably appealing for clinical practice owing to its high fluorescence quantum yield, elevated US-triggered ROS generation efficiency, excellent aqueous stability and preferential accumulation in tumors 31 - 33 .…”