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Manganese(III) Phthalocyanine Complex Nanoparticle-Loaded Glucose Oxidase to Enhance Tumor Inhibition through Energy
Zhaoyang Liu1, Chao Li1, Yushi Cao1
1Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai 200234, China.
Abstract:
Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc-HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc-HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into •O2- and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.
Insights
This study introduces a novel nanoparticle (MnClPc-HSA@GOx) that targets cancer by reducing tumor cell energy metabolism and reprogramming tumor-associated macrophages (TAMs) to fight inflammation. This dual-action approach shows promise for effective cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Reactive oxygen species (ROS) show potential in cancer treatment by altering the tumor microenvironment and macrophage polarization.
- Limitations of ROS therapy include transient nature and limited diffusion, hindering clinical application.
- Tumor-associated macrophages (TAMs) play a crucial role in cancer progression, with M2 (anti-inflammatory) and M1 (pro-inflammatory) phenotypes.
Purpose of the Study:
- To develop a nanoparticle system for enhanced cancer treatment.
- To inhibit tumor energy metabolism and induce M2 to M1 TAM polarization.
- To overcome the limitations of traditional ROS-based therapies.
Main Methods:
- A nanoparticle (MnClPc-HSA@GOx) was synthesized, combining manganese phthalocyanine (MnClPc), human serum albumin (HSA), and glucose oxidase (GOx).
- GOx catalyzed glucose decomposition to produce hydrogen peroxide (H2O2), which was further converted to ROS (•O2− and 1O2) by MnClPc.
- The nanoparticle's effect on tumor cell metabolism and TAM polarization was evaluated.
Main Results:
- The MnClPc-HSA@GOx nanoparticle effectively inhibited tumor cell glucose supply and energy metabolism.
- ROS generated by the nanoparticle induced a shift in TAMs from the M2 to the M1 phenotype.
- This dual-action strategy resulted in significant tumor inhibition.
Conclusions:
- The developed nanoparticle offers a dual-action therapeutic strategy for cancer treatment.
- Targeting tumor metabolism and modulating TAMs presents a promising approach for overcoming ROS therapy limitations.
- This nanoparticle system holds potential for clinical applications in cancer therapy.
