Dual-Responsive and ROS-Augmented Nanoplatform for Chemo/Photodynamic/Chemodynamic Combination Therapy of Triple Negative Breast Cancer

Abstract

Integrating chemodynamic therapy (CDT) and photodynamic therapy (PDT) into one nanoplatform can produce much more reactive oxygen species (ROS) for tumor therapy. Nevertheless, it is still a great challenge to selectively generate sufficient ROS in tumor regions. Meanwhile, CDT and PDT are restricted by insufficient H 2 O 2 content in the tumor as well as by the limited tumor tissue penetration of the light source. In this study, a smart pH/ROS-responsive nanoplatform, Fe 2+ @UCM-BBD, is rationally designed for tumor combination therapy. The acidic microenvironment can induce the pH-responsive release of doxorubicin (DOX), which can induce tumor apoptosis through DNA damage. Beyond that, DOX can promote the production of H 2 O 2 , providing sufficient materials for CDT. Of note, upconversion nanoparticles at the core can convert the 980 nm light to red and green light, which are used to activate Ce6 to produce singlet oxygen ( 1 O 2 ) and achieve upconversion luminescence imaging, respectively. Then, the ROS-responsive linker bis-(alkylthio)alkene is cleaved by 1 O 2 , resulting in the release of Fenton reagent (Fe 2+ ) to realize CDT. Taken together, Fe 2+ @UCM-BBD exhibits on-demand therapeutic reagent release capability, excellent biocompatibility, and remarkable tumor inhibition ability via synergistic chemo/photodynamic/chemodynamic combination therapy.

Current Use of Fenton Reaction in Drugs and Food

“…Lei et al prepared pH-responsive nanoparticles co-encapsulated with DOX and APAP, which were released at 56.5% and 61.8%, respectively, under an acidic endosomal/lysosomal environment, synergistically promoting OH • generation by the Fenton reaction [ 86 ]. Cho et al prepared dual (pH- and redox-)responsive magnetic nanoparticles that promote drug release under low pH and high GSH concentrations [ 87 ], and Chen et al developed a pH/ROS-responsive multifunctional nanoplatform that inhibits tumor through chemo/photodynamic/chemodynamic combinations [ 88 ]. Jia et al prepared multifunctional nanoparticles with a core-shell structure encapsulating Fe 3 O 4 and demonstrated that simultaneous photothermal and chemodynamic therapy is possible [ 89 ].…”

Ultrasmall AgBiSe2 nanodots for CT/thermal imaging-guided photothermal tumor therapy in the NIR-II biowindow

“…Overall, the results of western blotting and apoptosis analysis illustrate that the photothermal performance of AgBiSe 2 under 1064 nm NIR irradiation can upregulate the expression of Hsp70 and Cas 3 in 4T1 cells, thus inducing apoptosis and necrosis, and finally causing cell death. 53,54…”

Self-Supply Oxygen ROS Reactor via Fenton-like Reaction and Modulating Glutathione for Amplified Cancer Therapy Effect

“…However, the insufficient concentration of H 2 O 2 in TME limits the practical application [ 22 , 23 ]. PDT is also a ROS-mediated therapy with spatio-temporal selectivity in response to localized specific laser stimulation [ 24 ], which generates highly cytotoxic ROS ( 1 O 2 ) by transferring light energy to surrounding O 2 through localized light radiation. However, PDT is heavily dependent on tissue oxygen concentration.…”