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 region 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. Graphical Abstract

A mitochondria-anchored supramolecular photosensitizer as a pyroptosis inducer for potent photodynamic therapy and enhanced antitumor immunity

“…Mitochondria have been demonstrated as a pivotal target in drug design of cancer and other diseases, particularly as a critical photooxidation target in PDT [ 44 , 45 ]. As ROS possess very limited diffusion region (< 0.02 μm) and short half-life span (∼3.5 μs), the intracellular distribution of photosensitizers coincides with the photodamaged sites [ 46 – 48 ]. Therefore, photosensitizers capable of mitochondria localization ability actually enhance the efficiency of ROS, ultimately increasing the efficacy of PDT [ 27 , 49 , 50 ].…”

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

“…PFAS are ubiquitous environmental contaminants that are known to adversely affect various bodily systems, including the female reproductive system (2,5–9,45,46,10). PFAS have been associated with adverse health effects in uterine and ovarian tissue, as well as increased risk of reproductive disorders such as PCOS and even cancer (5–7,9,11,47–49). Our recent study (12) linked exposure to select PFAS with platinum resistance in ovarian cancer.…”

A chemical biology toolbox to overcome the hypoxic tumor microenvironment for photodynamic therapy: a review

“…To modulate cellular oxygen consumption at tumor target sites, Wen et al loaded the photosensitizer IR780 and the oxygen regulator 3-bromopyruvate 3BP on a polylactic–glycolic acid (PLGA) nanoplatform. 61 As a biocompatible antitumor agent, 3BP can block mitochondrial respiration and induce apoptosis. At the same time, 3BP can inhibit the glycolytic capacity of cells.…”