Mitochondria-Targeted Nanoplatforms For Enhanced Photodynamic Therapy Against Hypoxia Tumor

Abstract

Background: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers.Results: The as-synthesized nanoplatforms penetrated deeply into the interior regions of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment.Conclusions: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.

Photodynamic Priming Overcomes Per‐ and Polyfluoroalkyl Substance (PFAS)‐Induced Platinum Resistance in Ovarian Cancer†

“…Our findings demonstrating that DΨ m decreased following PDP are similar to those reported by others (78)(79)(80)(81)(82)(83)(84)(85). For example, Singh et al (84) reported that the fluorescence of Rhodamine-123, a dye that localizes to viable mitochondrial membranes, delocalized and filled the cell cytoplasm following PDT with Photofrin II as a photosensitizer, indicating that mitochondria are among the targets of Photofrin II-mediated PDT.…”

Carbon monoxide therapy: a promising strategy for cancer

“…For instance, the efficacy of several treatment methods, such as chemotherapy, radiotherapy, and immunotherapy, would be influenced by cancer-related hypoxia. [3][4][5] The abnormal characteristics of the tumor microenvironment are prone to form transport barriers, which limits the speed and range of drug delivery at the tumor site, 6 leading to a reduction in the efficacy of drugs. The application of conventional chemotherapy exerts different adverse effects.…”