Nano-Platelets as an Oxygen Regulator for Augmenting Starvation Therapy Against Hypoxic Tumor

Abstract

The restriction of a tumor’s energy supply is proven to be an effective means of treatment. Glucose oxidase (GOx), an enzyme that catalyzes the conversion of glucose to glucolactone, producing oxygen and hydrogen peroxide in the process, has proved useful in this regard. However, hypoxia, which is implicated in tumor growth, has been found to mediate resistance to this type of tumor starvation. Here, we describe the design and testing of a platelet membrane mimetic, PMS, consisting of mesoporous silica nanoparticles (MSNs) loaded with metformin (MET) as an inner layer and platelet membranes (PM) as an outer layer that inhibits oxygen consumption by the tumor cells’ respiratory pathways and enhances the effectiveness of GOx. MET directly inhibits the activity of complex I in mitochondrial electron transport and is thus a potent inhibitor of cell respiration. PMS target tumor tissue effectively and, once internalized, MET can inhibit respiration. When oxygen is plentiful, GOx promotes glucose consumption, allowing amplification of its effects on tumor starvation. This combination of respiratory suppression by PMS and starvation therapy by GOx has been found to be effective in both targeting tumors and inhibiting their growth. It is hoped that this strategy will shed light on the development of next-generation tumor starvation treatments.

The Use of Bionic Prodrugs for the Enhancement of Low Dose Radiotherapy

“…Tumor growth was partially suppressed by MT or low-dose RT (2 Gy) in isolation, while high-dose RY (6 Gy) achieved more pronounced antitumor efficacy, and maximal efficacy was observed in the MT + low-dose RT group, consistent with the radiosensitizing activity of MT (Figures 3B,C). No animals exhibited any significant body weight changes over the course of the study, consistent with a lack of nonspecific treatmentrelated toxicity (Figure 3D), which is of particular importance as many similar therapeutic approaches have been linked to systemic adverse events (Huang et al, 2020b). TUNEL and Ki-67 staining of tumors collected from these mice similarly confirmed that combination MT + RT treatment was linked to pronounced necrosis and apoptosis within tumors and a concomitant loss of tumor tissue (Figure 3E).…”

Glucose Metabolism Intervention-Facilitated Nanomedicine Therapy

“…A number of nanosystems carrying GOx have been synthetized to enhance ST by avoiding hazardous side effects and preventing degradation by proteinases. 42–44 To ensure long-lasting catalytic activity, Yang et al devised a nanovehicle to load GOx coordinated with folic acid and Zn 2+ termed GOx@PDA. 45 The nanodrug was further modified with a polydopamine (PDA) shell.…”

Novel Engineered Bacterium/Black Phosphorus Quantum Dot Hybrid System for Hypoxic Tumor Targeting and Efficient Photodynamic Therapy

“…In contrast to these oxygen supply-based strategies, Zhang et al instead developed an O 2 economizer that suppressed cellular respiration, thereby increasing oxygen availability for PDT or other relevant applications. Tumors, however, are heterogeneous, with many tumor tissues not exhibiting hypoxia. − Many of these experimental systems designed to treat intratumoral hypoxia do not exhibit specific targeting to hypoxic tissue sites, which are commonly found deep within the core of tumor tissues. − Traditional nanocarriers are generally unable to efficiently penetrate these deep tissue sites, limiting their therapeutic utility. − There is thus an urgent need for the development of a hypoxia-specific tumor therapeutic platform that can bolster intratumoral oxygen levels and enhance PDT efficacy.…”