Progress in hypoxic tumor therapy using graphdiyne-based nanocomposite

Data:2020-07-03  |  【 A  A  A 】  |  【Print】 【Close

The teams from Prof. Chunying Chen in NCNST, Prof. Huibiao Liu in ICCAS, and Prof. Xingfa Gao in Jiangxi Normal University made a progress in hypoxic tumor therapy by two-dimensional graphdiyne-based nanocomposites. The research was published and titled “Graphdiyne-templated palladium-nanoparticle assembly as a robust oxygen generator to attenuate tumor hypoxia” (Nano Today, 2020, 34, 100907).
Hypoxia is one of the important features of solid tumor, which is highly related to the tumorigenesis and tumor progression. It is important to overcome tumor hypoxia and increase its local oxygen concentration during tumor therapy. In recent years, many nanomaterials with enzyme-like activity have been reported that can be applied in tumor hypoxia therapy. However, most of nanocatalysts are facile to be aggregated or be degraded that largely decreases catalytic activity. As a result, unstable status of nanocatalysts hinders the long-term and efficient therapies. Therefore, it is urgent to maintain high stability and activity of the nanocatalysts for long-term therapies.
Graphdiyne (GDY) is a novel two-dimensional nanomaterial with both sp- and sp2-hybridized carbon atoms, which has large conjugated system and diverse carbon bonds. Based on these properties of GDY, Prof. Chen’s group designed a stable and high-performance oxygen generator, palladium nanoparticles (PdNPs)/GDY composite. The spaced sp-/sp2-hybridized carbon atoms, regular nanopores and high coordination ability of π-bonds provide stable binding sites for metal-based nanocatalysts, and prevent nanocatalysts from aggregation or degradation, which maintains the sustained catalytic ability. As reported, PdNPs/GDY nanocomposite could efficiently decompose hydrogen peroxide (H2O2) into O2 and still maintains high activity after tens of catalytic cycles. The stability of PdNPs/GDY is much higher than PdNPs, PdNPs/graphene nanocomposite and commercial Pd/C. To figure out the mechanism, researchers captured the intermediates of PdNPs/GDY and H2O2 during catalytic reaction using in situ methods by combining X-ray absorption spectroscopy (XAS) with electron spin resonance (ESR) techniques. DFT calculations further revealed its catalytic mechanism. Furthermore, they performed in vitro experiments and patient-derived xenograft (PDX) model experiment. They found that PdNPs/GDY decomposed endogenous H2O2 in tumor cells efficiently and continuously, attenuated tumor hypoxia, downregulated the expression of HIF-1α, and finally delayed tumor growth. Moreover, in the combination with the chemotherapeutic agent, doxorubicin, PdNPs/GDY-based catalytic therapy achieved a significantly enhanced antitumor effect. With high biocompatibility, low toxicity and highly antitumoral ability, GDY and its composites thus have great promise in biomedical application as novel nanomedicines. These in-situ analytical techniques for catalytic reaction study also provides new insights in understanding the behaviors of nanomaterials, such as catalysis, redox, and bio/chemical transformation.
Here, Mr. Jiaming Liu (NCNST), Dr. Liming Wang (Institute of High Energy Physics, Chinese Academy of Sciences), and Dr. Xiaomei Shen (Jiangxi Normal University) contributed equally to this work. Prof. Chen, Prof. Liu, and Prof. Gao were the corresponding authors. This work was financially supported by MSOT, NSFC, CAS, and Synchrotron Radiation Facilities.
 

Figure 1. Schematic diagrams about the synthesis and chemical structure of PdNPs/GDY

Figure 2. Application of in situ methods in exploring catalytic mechanism and the use of PdNPs/GDY as an oxygen generator for hypoxic tumor therapy

It is worth mentioning that Prof. Chunying Chen’s group has devoted to developing multiple analytical methods to characterize nanomaterials in biological systems, most of which are based on synchrotron radiation facilities (Chemical Society Reviews 2013, 42, 8266-8303; Anal Chem 2018, 90 (1), 589-614; Acc. Chem. Res. 2019, 52 (6), 1507-1518). These analytical methods show high resolution, high sensitivity, and non-destructiveness for elements. These methods have been applied in the quantitative analysis at nano-bio interfaces, such as the interactions between nanomaterials and proteins or phospholipids (J. Am. Chem. Soc. 2013, 135 (46), 17359-17368;ACS Nano 2019, 13 (8), 8680-8693; ACS Nano 2020, 14 (5), 5529-5542). They can quantitatively characterize chemical behavior of nanomaterials in biological systems, such as redox, degradation, chemical transformation, and catalysis (ACS Nano 2016, 10 (4), 4587-4598; this work). They can be also used for high-resolution imaging as well as in-situ analysis for chemical states at single particle, single cell, and tissue levels (ACS Nano 2015, 9 (6), 6532-6547; Advanced Materials 2016, 28 (40), 8950-8958). These analytical methods offer systematic strategies to study the distribution, chemical states, and nano-bio interfaces of nanomaterials during biomedical application of nanomaterials. Moreover, these analytical methods have attracted world-wide scientists’ attention. Some of them have been introduced in Encyclopedia of Analytical Chemistry and were highlighted to “open the door for innovative solutions and strategies” in analytical methods for nanomaterials in biomedical study. These analytical methods will probably promote the study of biomedical effects of nanomaterials.

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