Synthesis of multi-branched Au nanocomposites with distinct plasmon resonance in NIR-II window and controlled CRISPR-Cas9 delivery for synergistic gene-photothermal therapy (2022)

Table of Contents
Biomaterials Abstract Graphical abstract Introduction Section snippets Results and discussion Conclusion Credit author statement Data availability Declaration of competing interest Acknowledgements References (62) Chem. Eng. J. Smart Mater. Med. Chem. Eng. J. Biomaterials Biomaterials Chem. Eng. J. Acta Biomater. Bioact. Mater. J. Contr. Release Biomaterials Nano Today Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer Chem. Soc. Rev. Near-infrared light-responsive nanomaterials in cancer therapeutics Chem. Soc. Rev. Yolk–shell structured Au [emailprotected]–organic framework for synergistic chemo-photothermal therapy in the second near-infrared window Nano Lett. Overview of the application of inorganic nanomaterials in cancer photothermal therapy Biomater. Sci. Using binary surfactant mixtures to simultaneously improve the dimensional tunability and monodispersity in the seeded growth of gold nanorods Nano Lett. Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and chemotherapy of cancer Adv. Mater. Carbon nanotubes as photoacoustic molecular imaging agents in living mice Nat. Nanotechnol. Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy J. Am. Chem. Soc. Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles Nat. Commun. Facile syntheses of conjugated polymers for photothermal tumour therapy Nat. Commun. Second near-infrared photothermal materials for combinational nanotheranostics Chem. Soc. Rev. Gold nanoparticles for biology and medicine Angew. Chem. Int. Ed. Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies Chem. Soc. Rev. Understanding the photothermal conversion efficiency of gold nanocrystals Small Exceptionally high payload of doxorubicin in hollow gold nanospheres for near-infrared light-triggered drug release ACS Nano Plasmonic photothermal nanoparticles for biomedical applications Adv. Sci. From gold nanobipyramids to nanojavelins for a precise tuning of the plasmon resonance to the infrared wavelengths: experimental and theoretical aspects Nanoscale Compact plasmonic blackbody for cancer theranosis in the near-infrared II window ACS Nano Fine-Tuning the homometallic interface of Au-on-Au nanorods and their photothermal therapy in the NIR-II window Angew. Chem. Int. Ed. 1D coordination polymer nanofibers for low-temperature photothermal therapy Adv. Mater. Cited by (0) Recommended articles (6)
ScienceDirect

Corporate sign inSign in / register

ViewPDF

  • Access throughyour institution

Biomaterials

Volume 287,

August 2022

, 121621

Abstract

Clinical implementation of photothermal therapy (PTT) is mainly hampered by limited tissue penetration, undesirable thermal damage to normal tissues, and thermotolerence induced by heat shock proteins (HSPs). To overcome these obstacles, we constructed a novel gene-photothermal synergistic therapeutic nanoplatform composed of a multi-branched Au nanooctopus (AuNO) core and mesoporous polydopamine (mPDA) shell, followed by CRISPR–Cas9 ribonucleoprotein (RNP) loading and then polyethylene glycol-folic acid (PEG-FA) coating. AuNO was simply synthesized by adjusting the ratio of cetyltrimethylammonium chloride (CTAC) and cetyltrimethylammonium bromide (CTAB), which showed significant localized surface plasmon resonances in the NIR-II window, and exhibited an excellent tissue penetration capability and high photothermal conversion efficiency (PCE, 47.68%). Even, the PCE could be further increased to 66.17% by mPDA coating. Furthermore, the sequential modification of [emailprotected] using RNP and PEG-FA can down-regulate HSP90α expression at tumor sites, enhance apoptosis and reduce the heat resistance of cancer cells. The synergistic effect of enhanced photothermal capacity and reduced thermoresistance addressed the multiple limitations of PTT, and presented excellent in vitro and in vivo antitumor efficacy, having great potential for the clinical application of PTT.

Graphical abstract

A targeted synergistic platform of gene-photothermal therapy is established by synthesizing multibranched Au nanooctopus, followed by coating with mesoporous polydopamine, loading with CRISPR-Cas9 and decorating with polyethylene glycol-folic acid. This platform shows a significantly augmented antitumor efficacy of PTT and diminished side effects through the synergy of enhancing photothermal capability in NIR-Ⅱ window conferred by Au nanooctopus and reducing thermoresistance by downregulating heat shock proteins conferred by CRISPR-Cas9 editing.

Synthesis of multi-branched Au nanocomposites with distinct plasmon resonance in NIR-II window and controlled CRISPR-Cas9 delivery for synergistic gene-photothermal therapy (5)
  1. Download : Download high-res image (315KB)
  2. Download : Download full-size image

Introduction

Photothermal therapy (PTT) based on photothermal nanoagents (PTAs) has revolutionized oncology treatment owing to the unique merits, such as precise spatial-temporal resolution and minimal invasiveness [[1], [2], [3], [4]]. Typically, PTT utilizes the local hyperthermia produced by PTAs upon light irradiation to ablate tumor cells. Over the past years, great advances have been made in the synthesis of PTAs with light absorption in biological windows, including the first near-infrared (NIR-I, 750–1000nm) window and the second near-infrared (NIR-II, 1000–1350nm) window [[5], [6], [7], [8], [9], [10], [11]]. Nevertheless, most PTAs with light absorption in the NIR-I region exhibit limited penetration, which may lead to the survival of tumor cells outside the irradiation range [12]. Moreover, overheating of the tumor region may cause unfavorable damage to surrounding normal tissues, along with heat resistance of tumor cells activated by abnormally upregulated heat shock proteins (HSPs). Thus, developing a general strategy to overcome these inherent drawbacks is highly desired for the clinical application of PTT.

During PTT therapy, the limited penetration of NIR-I light is mainly attributed to light diffusion and absorption by endogenous biological tissues, which can be efficiently mitigated by shifting the light range from the NIR-I window to the NIR-II window [13]. Therefore, it is essential to develop PTAs with significant absorption in the NIR-II window. Currently, various PTAs based on NIR-II light have been developed [1,13,14], and Au-based nanostructures have attracted increasing interest due to their multiple structural remodeling [5,15], favorable biological behavior [16,17], and excellent photothermal conversion capability in the NIR region [18,19]. The NIR absorption of Au nanostructures originates from their localized surface plasmon resonances (LSPRs) and is closely related to their shape. Given the facile control of synthetic parameters, diverse Au nanostructures have been synthesized [20,21]. For example, Au nanorods or nanobipyramids with broadly tunable longitudinal LSPRs have been prepared using a binary surfactant mixture and are widely applied in PTT [6,22,23]. Alternatively, blackbody-like nanomaterials with hyperbranched structures were synthesized with the help of ligands and showed excellent photothermal capabilities in the NIR-II window [24,25]. Even so, Au-based PTAs with remarkable NIR-II absorption, high photothermal conversion efficiency (PCE) and excellent antitumor effects, still remians to be developed.

To overcome tumor thermoresistance, the combination of hyperthermia and HSPs inhibition has been studied in several reports [[26], [27], [28], [29]]. Although common strategies that use small molecule inhibitors against HSPs have relatively enhanced the efficacy of tumor ablation, these treatments still lack spatial and temporal control over drug release, leading to unavoidable systemic toxicity, which may even overshadow the shining points of PTT. Recently, gene editing of clustered regularly interspaced short palindromic repeat (CRISPR)-associated 9 (CRISPR–Cas9) has been recognized as a powerful tool to realize controlled gene editing [30,31]. More importantly, the flexible release of CRISPR–Cas9 into the nucleus can reduce off-target effects and achieve low cytotoxicity and high genome editing efficiency [32]. Previous studies have demonstrated that CRISPR-Cas9 ribonucleic acid proteins suppress the expression of HSPs through precise and controlled release by light/photothermal heat, providing a potential strategy to achieve synergistic and mild PTT effects [33,34]. However, the current combination of CRISPR–Cas9 and PTT mainly employs PTAs with absorption in the NIR-I window or non-ideal PCE [30,31,[34], [35], [36]]. To combat deep-seated tumors with minimal damage to surrounding tissues, it is highly desirable to integrate CRISPR–Cas9 with novel PTAs with distinct NIR-II absorption and excellent PCE.

In this work, we creatively establish a targeted synergistic gene-photothermal therapuetic platform composed of a multi-branched Au nanooctopus (AuNO) core, and a mesoporous polydopamine (mPDA) shell loaded with CRISPR–Cas9 ribonucleoprotein (RNP) and coated with a polyethylene glycol-folic acid (PEG-FA), denoted as [emailprotected]–Cas9-PEG-FA (AP-RNP-F, Fig. 1a). Because PEG-FA prolongs blood circulation and confers active targeting, AP-RNP-F can be efficiently delivered into tumor cells. After endocytosis, the release of Cas9 RNP into the nucleus can be precisely triggered by acid and NIR irradiation. Depletion of HSP90α by Cas9 RNP then renders tumor cells susceptible to mild hyperthermia generated by [emailprotected] (AP) under NIR-II irradiation, leading to apoptosis of tumor cells and survival of surrounding normal cells. Overall, this platform combines the high photothermal capacity of AP with the thermal resistance overcome by silencing the HSP gene, greatly improving the antitumor efficacy of PTT and reducing the side effects on normal tissues (Fig. 1b).

Section snippets

Results and discussion

A series of anisotropic Au nanostructures with tunable LSPRs were synthesized by seed-mediated growth method in a modified binary surfactants system composed of cetyltrimethylammonium chloride (CTAC) and cetyltrimethylammonium bromide (CTAB) (Fig. 2a and Table S1, Supporting Information) [37]. Specifically, the seeds were synthesized through HAuCl4 reduction by NaBH4 and stabilized with citric acid (CA) and CTAC, and then dropped rapidly into the growth solution containing HAuCl4, AgNO3

Conclusion

In summary, we reported a facile synthesis of multibranched Au nanostructures and their combination with controlled delivery of CRISPR–Cas9 ([emailprotected]–Cas9-PEG-FA) for PTT with enhanced penetration and reduced thermoresistance. The superior LSPRs of AuNO in the NIR-II region endow photothermal nanoagents with deep tissue penetration and excellent photothermal conversion properties. The mPDA coating of the Au core further improves the PCEs, enables targeted delivery and triggered release

Credit author statement

M. Z., J. D. and Y. M. conceived the project. W. T. and X. C. designed and supervised the experiments. N. W. performed the material experiments. J. R. and Y. G. performed the biological experiments. D. S., Y. H. and M. Z. took part in analyzed data. T. Z., H. F. and L. F. took part in discussions. W. T., N. W. and C. L. wrote the first paper draft. All authors discussed the results and commented on the manuscript.

Data availability

The data supporting this study are primarily contained within the manuscript itself along with relevant supplementary materials, and are otherwise available from the corresponding author upon request.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by the National Natural Science Foundation of China (81873096, 81403041). Blue Project of Jiangsu Province for excellent young and middle-aged teachers and principals of universities in Jiangsu province. Major Projects of Natural Science Research in Universities of Jiangsu Province (No. 19KJA310007). A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

References (62)

  • D. She et al.Biomimic FeS2 nanodrug with hypothermal photothermal effect by clinical approved NIR-Ⅱ light for augmented chemodynamic therapy

    Chem. Eng. J.

    (2020)

  • Z. Li et al.Charge-reversal nanomedicines as a smart bullet for deep tumor penetration

    Smart Mater. Med.

    (2022)

  • W. Zeng et al.Dual-response oxygen-generating MnO2 nanoparticles with polydopamine modification for combined photothermal-photodynamic therapy

    Chem. Eng. J.

    (2020)

  • D. Wu et al.Mesoporous polydopamine with built-in plasmonic core: traceable and NIR triggered delivery of functional proteins

    Biomaterials

    (2020)

  • L. Li et al.Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities

    Biomaterials

    (2018)

  • Y. Xu et al.High-yield synthesis of gold bipyramids for in vivo CT imaging and photothermal cancer therapy with enhanced thermal stability

    Chem. Eng. J.

    (2019)

  • A.S.C. Gonçalves et al.Strategies to improve the photothermal capacity of gold-based nanomedicines

    Acta Biomater.

    (2020)

  • T. Chen et al.Engineered gold/black phosphorus nanoplatforms with remodeling tumor microenvironment for sonoactivated catalytic tumor theranostics

    Bioact. Mater.

    (2022)

  • F. Zhang et al.Magnetic nanoparticles coated with polyphenols for spatio-temporally controlled cancer photothermal/immunotherapy

    J. Contr. Release

    (2020)

  • Z. Yu et al.Near-infrared-II activated inorganic photothermal nanomedicines

    Biomaterials

    (2021)

  • S. Gai et al.Recent advances in functional nanomaterials for light–triggered cancer therapy

    Nano Today

    (2018)

  • Y. Liu et al.

    Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer

    Chem. Soc. Rev.

    (2019)

  • V. Shanmugam et al.

    Near-infrared light-responsive nanomaterials in cancer therapeutics

    Chem. Soc. Rev.

    (2014)

  • X. Deng et al.

    Yolk–shell structured Au [emailprotected]–organic framework for synergistic chemo-photothermal therapy in the second near-infrared window

    Nano Lett.

    (2019)

  • N. Fernandes et al.

    Overview of the application of inorganic nanomaterials in cancer photothermal therapy

    Biomater. Sci.

    (2020)

  • X. Ye et al.

    Using binary surfactant mixtures to simultaneously improve the dimensional tunability and monodispersity in the seeded growth of gold nanorods

    Nano Lett.

    (2013)

  • T. Liu et al.

    Drug delivery with PEGylated MoS2 nano-sheets for combined photothermal and chemotherapy of cancer

    Adv. Mater.

    (2014)

  • A. De La Zerda et al.

    Carbon nanotubes as photoacoustic molecular imaging agents in living mice

    Nat. Nanotechnol.

    (2008)

  • J.T. Robinson et al.

    Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy

    J. Am. Chem. Soc.

    (2011)

  • Z. Zhao et al.

    Highly efficient photothermal nanoagent achieved by harvesting energy via excited-state intramolecular motion within nanoparticles

    Nat. Commun.

    (2019)

  • P. Chen et al.

    Facile syntheses of conjugated polymers for photothermal tumour therapy

    Nat. Commun.

    (2019)

  • C. Xu et al.

    Second near-infrared photothermal materials for combinational nanotheranostics

    Chem. Soc. Rev.

    (2021)

  • D.A. Giljohann et al.

    Gold nanoparticles for biology and medicine

    Angew. Chem. Int. Ed.

    (2010)

  • N. Khlebtsov et al.

    Biodistribution and toxicity of engineered gold nanoparticles: a review of in vitro and in vivo studies

    Chem. Soc. Rev.

    (2011)

  • H. Chen et al.

    Understanding the photothermal conversion efficiency of gold nanocrystals

    Small

    (2010)

  • J. You et al.

    Exceptionally high payload of doxorubicin in hollow gold nanospheres for near-infrared light-triggered drug release

    ACS Nano

    (2010)

  • M. Kim et al.

    Plasmonic photothermal nanoparticles for biomedical applications

    Adv. Sci.

    (2019)

  • D. Chateau et al.

    From gold nanobipyramids to nanojavelins for a precise tuning of the plasmon resonance to the infrared wavelengths: experimental and theoretical aspects

    Nanoscale

    (2015)

  • J. Zhou et al.

    Compact plasmonic blackbody for cancer theranosis in the near-infrared II window

    ACS Nano

    (2018)

  • J. Jia et al.

    Fine-Tuning the homometallic interface of Au-on-Au nanorods and their photothermal therapy in the NIR-II window

    Angew. Chem. Int. Ed.

    (2020)

  • Y. Yang et al.

    1D coordination polymer nanofibers for low-temperature photothermal therapy

    Adv. Mater.

    (2017)

  • Cited by (0)

    Recommended articles (6)

    • Research article

      Liver ductal organoids reconstruct intrahepatic biliary trees in decellularized liver grafts

      Biomaterials, Volume 287, 2022, Article 121614

      Three-dimensional scaffolds decellularized from native organs are a promising technique to establish engineered liver grafts and overcome the current shortage of donor organs. However, limited sources of bile duct cells and inappropriate cell distribution in bioengineered liver grafts have hindered their practical application. Organoid technology is anticipated to be an excellent tool for the advancement of regenerative medicine. In the present study, we reconstructed intrahepatic bile ducts in a rat decellularized liver graft by recellularization with liver ductal organoids. Using an ex vivo perfusion culture system, we demonstrated the biliary characteristics of repopulated mouse liver organoids, which maintained bile duct markers and reconstructed biliary tree-like networks with luminal structures. We also established a method for the co-recellularization with engineered bile ducts and primary hepatocytes, revealing the appropriate cell distribution to mimic the native liver. We then utilized this model in human organoids to demonstrate the reconstructed bile ducts. Our results show that liver ductal organoids are a potential cell source for bile ducts from bioengineered liver grafts using three-dimensional scaffolds.

    • Research article

      Aggregation-induced emission (AIE)-Based nanocomposites for intracellular biological process monitoring and photodynamic therapy

      Biomaterials, Volume 287, 2022, Article 121603

      As a non-invasive visualization technique, photoluminescence imaging (PLI) has found its huge value in many biological applications associated with intracellular process monitoring and early and accurate diagnosis of diseases. PLI can also be combined with therapeutics to build imaging-guided theragnostic platforms for achieving early and precise treatment of diseases. Photodynamic therapy (PDT) as a quintessential phototheranostics technology has gained great benefits from the combination with PLI. Recently, aggregation-induced emission (AIE)-active materials have emerged as one of the most promising bioimaging and phototheranostic agents. Most of AIEgens, however, need to be chemically engineered to form versatile nanocomposites with improved their photophysical property, photochemical activity, biocompatibility, etc. In this review, we focus on three categories of AIE-active nanocomposites and highlight their application progresses in the intracellular biological process monitoring and PLI-guided PDT. We hope this review can guide further development of AIE-active nanocomposites and promote their practical applications for monitoring intracellular biological processes and imaging-guided PDT.

    • Research article

      Engineering dual catalytic nanomedicine for autophagy-augmented and ferroptosis-involved cancer nanotherapy

      Biomaterials, Volume 287, 2022, Article 121668

      Chemodynamic therapy represents a distinct anti-tumor strategy by activating intratumoral chemical catalytic reactions to produce highly toxic reactive oxygen species (ROS) from non-/limited-toxic nanocatalysts. However, the low efficacy of ROS generation still remains a major challenge for further clinical translation. Herein, a liposomal nanosystem which simultaneously encapsulated copper peroxide nanodots (CPNs) and artemisinin (ART) was constructed for autophagy-enhanced and ferroptosis-involved cancer cell death owing to Cu-based dual catalytic strategy. To be specific, the CPN components, served as a H2O2 self-supplying platform, release H2O2 and Cu2+ under acidic tumor environment and endogenously generate .OH via Fenton-like reaction (catalytic reaction I). In addition, Cu2+ species catalyze ART components to produce ROS radicals (catalytic reaction II), further augmenting the intracellular oxidative damage and lipid peroxide accumulation, leading to cancer cell death. Specifically, ART also acted as a potent autophagy inducer increasing the level of intracellular iron pool through degradation of ferritin, which could promote cancer cell ferroptosis, producing the best antineoplastic effect. After accumulation into the tumor sites, ultrasound irradiation was applied to trigger the release of CPNs and ART from liposomal nanosystems, and amplify the efficacy of catalytic reaction for maximum therapeutic effect. Both in vitro and in vivo therapeutic outcomes suggest the outstanding autophagy-augmented ferroptosis-involved cancer-therapeutic efficacy, which was further corroborated by transcriptome sequencing. In this work, Cu was firstly proven to trigger ART to produce ROS species, but also provide a TME-responsive nanoplatform for potentially suppressing tumor growth by autophagy-augmented ferroptosis-involved cancer nanotherapy.

    • Research article

      Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer

      Biomaterials, Volume 287, 2022, Article 121599

      The compact extracellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC) is the major physical barrier that hinders the delivery of anti-tumor drugs, leading to strong inherent chemotherapy resistance as well as establishing an immunosuppressive tumor microenvironment (TME). However, forcibly destroying the stroma barrier would break the balance of delicate signal transduction and dependence between tumor cells and matrix components. Uncontrollable growth and metastasis would occur, making PDAC more difficult to control. Hence, we design and construct an aptamer-decorated hypoxia-responsive nanoparticle s(DGL)n@Apt co-loading gemcitabine monophosphate and STAT3 inhibitor HJC0152. This nanoparticle can reverse its surficial charge in the TME, and reduce the size triggered by hypoxia. The released ultra-small DGL particles loading gemcitabine monophosphate exhibit excellent deep-tumor penetration, chemotherapy drugs endocytosis promotion, and autophagy induction ability. Meanwhile, HJC0152 inhibits overactivated STAT3 in both tumor cells and tumor stroma, softens the stroma barrier, and reeducates the TME into an immune-activated state. This smart codelivery strategy provides an inspiring opportunity in PDAC treatment.

    • Research article

      Photo-enhanced upcycling H2O2 into hydroxyl radicals by IR780-embedded Fe3O4@MIL-100 for intense nanocatalytic tumor therapy

      Biomaterials, Volume 287, 2022, Article 121687

      Reactive oxygen species (ROS)-based nanocatalytic tumor therapy is alluring owing to the capability to generate highly cytotoxic ∙OH radicals from tumoral H2O2. However, the antitumor efficacy is highly dependent on the radical generation efficiency and challenged by the high levels of antioxidative glutathione (GSH) in cancer cells. Herein, we report an IR-780 decorated, GSH-depleting Fe3O4@MIL-100 (IFM) nanocomposite for photo-enhanced tumor catalytic therapy by extensive production of ∙OH, which is realized by an integration of excellent peroxidase-like activity of IFM, selective upregulation of tumoral H2O2 by β-lapachone, and localized hyperthermia by near infrared light irradiation. IFM shows potentiated antiproliferative effect in 4T1 cancer cells by ∙OH overproduction and glutathione scavenging, inducing intracellular redox dyshomeostasis and cell death by concurrent apoptosis and ferroptosis. In vivo antitumor investigation further demonstrates photoacoustic and fluorescence imaging-guided combinational therapy with a tumor inhibition rate of 96.4%. This study provides a strategy of photo-enhanced nanocatalytic tumor therapy by tumor-specific H2O2 amplification and hyperthermia.

    • Research article

      A platinum nanourchin-based multi-enzymatic platform to disrupt mitochondrial function assisted by modulating the intracellular H2O2 homeostasis

      Biomaterials, Volume 286, 2022, Article 121572

      Endogenous H2O2 sacrifices for diversified therapeutic reactions against tumor. However, the treatment outcome is not always satisfactory owing to the unsustainable H2O2 supply from tumor microenvironment (TME). Herein, a platinum (Pt) nanourchin-based multi-enzymatic platform (referred to PGMA) is established by surface conjugation of glucose oxidase (GOx) capped with manganese carbonyl (MnCO) and loading 3-amino-1,2,4-triazole (3-AT). The mild acidic and H2O2-rich TME can render the degradation of MnCO, followed by triggering the release of CO gas, 3-AT and Mn2+/3+. The resultant GOx exposure initiates intratumoral glucose depletion, which is promoted by the O2 replenishment through Pt-catalyzed decomposition of H2O2. Meanwhile, intracellular reactive oxygen species (ROS) level is elevated through Mn2+/3+ couple-mediated Fenton-like reaction. Hence, CO release-initiated gas therapy, glucose exhaustion-induced tumor starvation and ROS-triggered chemodynamic therapy are committed to realizing a combinatorial disruption effect on mitochondrial function. Importantly, the released 3-AT can inhibit the activity of endogenous catalase, which effectively elevates the intracellular H2O2 level to compensate its consumption and provides incremental reactant for cascade utilizations. Taken together, this study aims to emphasize the importance of intracellular H2O2 balance during H2O2-depleted therapeutic process, and affords a prime paradigm of applying this strategy for tumor treatment via mitochondrial dysfunction.

    View full text

    © 2022 Elsevier Ltd. All rights reserved.

    Top Articles

    Latest Posts

    Article information

    Author: Carlyn Walter

    Last Updated: 12/21/2022

    Views: 6061

    Rating: 5 / 5 (70 voted)

    Reviews: 93% of readers found this page helpful

    Author information

    Name: Carlyn Walter

    Birthday: 1996-01-03

    Address: Suite 452 40815 Denyse Extensions, Sengermouth, OR 42374

    Phone: +8501809515404

    Job: Manufacturing Technician

    Hobby: Table tennis, Archery, Vacation, Metal detecting, Yo-yoing, Crocheting, Creative writing

    Introduction: My name is Carlyn Walter, I am a lively, glamorous, healthy, clean, powerful, calm, combative person who loves writing and wants to share my knowledge and understanding with you.