Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy

doi:10.1016/j.nantod.2020.101073

Nano Today

Volume 37, April 2021, 101073

https://doi.org/10.1016/j.nantod.2020.101073 Get rights and content

Highlights

•
This review summarizes the developments of NIR photoactivated nanomedicines for photothermal synergistic cancer therapy.
•
The designing principles, working mechanisms and applications of NIR photoactivated nanomedicines are introduced.
•
The existing challenges and further perspectives of NIR photoactivated nanomedicines are also discussed.

Abstract

Cancer nanomedicines have provided promising treatment strategies for the regression of several types of cancer, although there still exists a need for significant advances to improve their therapeutic outcomes and reduce side effects. In this context, photothermal therapy (PTT) that uses near-infrared (NIR) photoirradiation of photothermal agents to generate heat for localized thermal damages has been established as a safe therapeutic modality. In addition to direct ablation of tumors, the heat generated during PTT process can achieve on-demand release of other therapeutic compounds, regulation of gene transcription and enzyme activity and enhancement of chemical reactions in tumor tissues, thereby resulting in photothermal synergistic cancer therapy with obviously improved benefits. In this review, we summarize the recent developments in NIR photoactivated nanomedicines for photothermal synergistic cancer therapy. We introduce the designing principles and the working mechanisms of nanoparticles upon NIR photoirradiation and their applications in photothermal synergistic chemotherapy, enzyme therapy, gene therapy, photodynamic therapy, chemodynamic therapy, thermodynamic therapy, immunotherapy and their multimodal therapies for cancer. Moreover, we discuss the existing challenges and further perspectives in this field.

Graphical Abstract

This review summarizes the recent development of near-infrared photoactivated nanomedicines for photothermal synergistic chemotherapy, enzyme therapy, gene therapy, photodynamic therapy, chemodynamic therapy, thermodynamic therapy, immunotherapy and multimodal therapies of cancer.

Introduction

Cancer therapy remains a significant challenge in the clinical setting because traditional therapeutic strategies (such as surgery and radiotherapy) often lead to poor therapeutic efficacies and/or adverse side effects [1], [2], [3]. With the development of various nanoparticle platforms with diverse physicochemical properties, nanomedicines have provided hopeful chances for cancer treatment [4], [5], [6]. Nanomaterials was able to preferentially accumulate into tumor areas to deliver therapeutic agents by passive or active targeting effect [7], [8], [9]. Furthermore, nanoparticles can be designed to realize the activation of therapeutic actions in response to biomarkers in tumor microenvironment (pH, redox potential and enzymes) or external stimuli (light, magnetic force, ultrasound and X-rays) [10], [11], [12], [13], [14], [15], [16], [17]. Such nanoparticle strategies have significantly improved the curative effect and potentially avoided side effects [18], [19], [20].

Photothermal therapy (PTT) has served as an attractive therapeutic modality for cancer because of its advantages of non-invasiveness, high temporal-spatial resolution and low toxicity concerns [21], [22], [23], [24]. During PTT, photothermal agents are irradiated by light at a specific wavelength to generate localized heat that can cause protein denaturation, DNA damage and cellular membrane destruction, which consequently result in selective ablation of tumor tissues [25], [26], [27]. Since NIR light (650–1700 nm) exhibits reduced absorption and scattering and can penetrate deeper into living organism than ultraviolet and visible light, NIR light has been widely used for PTT [28], [29], [30], [31]. To enhance the efficacy of heating, a large number of nanomaterials, including organic dye-based nanoparticles, organic polymer nanoparticles, carbon-based nanoparticles, metallic nanoparticles and inorganic semiconducting nanomaterials have been utilized as efficient photothermal agents for PTT of tumors [32], [33], [34], [35], [36], [37], [38].

Despite these promising potentials, use of PTT alone often results in failure to achieve complete eradication of tumor tissues, especially for larger tumors [39], [40], [41], [42], [43]. Therefore, combining PTT with other therapeutic modalities using nanomedicines is highly desirable to improve therapeutic outcomes [44], [45], [46], [47], [48], [49]. In this context, PTT-mediated thermal effects are demonstrated to obtain on-demand release of chemotherapeutic drugs from thermo-responsive nanocarriers [50]. Nanomaterial-enabled PTT can also induce the release of antigens and immune-stimulatory molecules by ablating tumors, thus promoting the activation of antitumor immunity [51], [52], [53]. In addition, PTT-induced temperature increases can regulate the biological events in living cells, such as enzyme activity and gene expression [54], [55], [56], [57], [58], [59]. Therefore, nanoparticle-mediated PTT has demonstrated a significant potential to synergize with different therapeutic strategies for cancer regression.

In this review, we outline the current developments of NIR photoactivated nanomedicines for photothermal synergistic cancer therapy. Upon NIR photoirradiation, these nanoparticles generate localized thermal effect, which not only exerts PTT but also allows for on-demand release of therapeutic agents, regulation of gene transcription and enzyme activity and enhancement of chemical reactions in tumors. The synergistic actions of PTT with chemotherapy, enzyme therapy, gene therapy, photodynamic therapy, chemodynamic therapy, thermodynamic therapy, immunotherapy and their multimodal therapies have been achieved. In the following sections, we shall introduce in detail the designing principles and the working mechanisms of NIR photoactivated nanomedicines and their corresponding applications for cancer therapy. Then, we provide a brief summary and discuss the actual challenges and further perspectives in this field.

Section snippets

Design of NIR photoactivated nanomedicines

PTT relies on photoexcitation of photothermal agents to produce heat for inducing cell apoptosis and tissue damage. Upon laser irradiation, photothermal agents transform from low excited singlet state (S₀) into excited singlet state (S₁) through absorbing a photon and exciting an electron [60]. As the S₁ state is highly unstable and short-lived state, they will return to S₀ state immediately, dissipating their energy by fluorescence emission or non-radiative vibrational relaxation [61]. The

Synergistic therapy between PTT and chemotherapy

Conventional chemotherapy, being the essential therapeutic strategy for malignant tumor or an adjunct approach for surgery or radiotherapy, has been widely used in clinical practice [64], [65], [66], [67], [68]. However, the effect of chemotherapy is often compromised by limited dosage, low drug level in tumor areas, chemotherapy-resistant and severe systemic toxicity [69], [70], [71]. Fortunately, NIR-responsive photothermal nanoplatforms, such as NIR-responsive thermosensitive materials

Synergetic therapy between PTT and nanoenzymes

Cancer therapy using enzymes has received widespread attention, because enzymes can effectively suppress malignant tumor growth by affecting biological functions at the molecular or cellular level, such as gene expression and anabolism in the organism [93], [94], [95], [96]. However, susceptibility, low enzymatic activity and limited maneuverability have restricted its further clinical applications [97]. Precise photothermic control of enzyme activity can not only securely manage the fate of

PTT-synergized gene therapy

As several thermosensitive gene elements in living cells, such as heat-shock protein 70 (HSP70) promoter, are susceptible to various stresses under physiological conditions, which endows PTA-mediated local hyperthermia within the physiological ranges to control gene expression [105], [106], [107], [108], [109]. For instance, Pu et al. synthesized a photothermal dendronized semiconducting polymer (DSP) gene nanocarrier for precise photothermal activation of gene expression [110]. The hydrophobic

Synergistic therapy between PTT and PDT

Photodynamic therapy (PDT) depends on photosensitizer (PS) that can transfer its excited triplet state energy to the oxygen molecule or substrates, in order to produce reactive oxygen species (ROS) [115], [116], [117]. This approach has been considered a promising and non-invasive treatment strategy against cancer; however, low selectivity and uncontrollable photoactivity of PS have limited its curative effect and clinical application to some extent [118], [119], [120], [121]. Therefore,

Synergistic therapy of PTT and CDT

Chemodynamic therapy (CDT), effectively generating hydroxyl radicals for killing cancer cells without oxygen via Fenton reaction, is a promising anticancer therapy [125], [126], [127], [128], [129]. However, limited by the insufficient H₂O₂ in cells and the catalytic efficiency, CDT, as a single treatment, possesses limited therapeutic effect, which prevents its further application [129], [130], [131], [132], [133], [134]. Notably, photothermal effect can serve as a stimulus to facilitate

PTT-synergized thermodynamic therapy (TDT)

Thermodynamic therapy (TDT), which has been defined as thermal decomposition of oxygen-independent free-radical sources, is considered as an emerging therapeutic modality [152]. Such oxygen-independent free-radical sources, such as azo initiator 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI), and 2,2′-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride (AIPH), could be rapidly decomposed under hyperthermia to generate 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)

PTT-synergized immunotherapy

Immunotherapy has demonstrated a great promise in cancer treatment, although it often suffers from major concerns of low patient response rates and potential immune-related adverse events in the clinic [166], [167], [168], [169]. PTT can induce immunogenic cell death of cancer cells to facilitate the maturation of dendritic cells (DCs) and the activation of immune cells, thereby initiating tumoricidal immunity [170], [171], [172], [173]. This process significantly improves the therapeutic

PTT-synergized multimodal therapies

PTT-synergistic bimodal therapy based on photoirradiation has showed better therapeutic effect than any monotherapy, but the potency of cancer therapy could be further improved by PTT-synergistic trimodal treatment based on the NIR-controlled co-operative interactions among multi-therapies [199], [200], [201], [202]. Better outcomes are expected through the fusion of various kinds of treatment models into a single nanomedicine.

The NIR-controlled tri-combination of PTT, chemotherapy and gene

Conclusion and outlook

Nanomedicines have provided new opportunities for treatment of cancer, while great efforts still need to be made to improve the curative outcomes and reduce the side effects. PTT that utilizes NIR photoirradiation of photothermal agents to generate localized heat for tumor ablation have shown unique superiorities over traditional therapeutic modalities. In addition, PTT-mediated thermal effect can be used for other actions, such as controlling release of therapeutic agents, regulating

CRediT authorship contribution statement

Haitao Sun, Qin Zhang, Jingchao Li: Resources, Visualization, Writing - original draft. Shaojun Peng, Xiaolin Wang, Rong Cai: Conceptualization, Supervision, Writing - review & editing, Funding acquisition.

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.

Acknowledgments

This work was supported by the Program for International S&T Cooperation Projects of the Ministry of Science and Technology of China (2018YFE0117200) and National Natural Science Foundation of China (Grant No. 81903165).

Haitao Sun received his B.S. degree in Zhongshan Hospital, Fudan university in 2018. He is now a Ph.D. candidate at Shanghai Institute of Medical Imaging, Fudan university under the supervision of Prof. Xiaolin Wang. His current research focuses on the fabrication of multifunctional and smart-responsive nanoparticles for cancer therapy.

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Qin Zhang is an assistant professor at Shanghai University in China. She received her Ph.D. in materials science and engineering in 2013 from the University of Tsukuba and National Center for Materials Science (NIMS) in Japan. Then, she worked as a postdoctoral research fellow at Tokyo Women’s Medical University in Japan and Zhejiang University in China, respectively. In 2020, she joined the Institute of Translational Medicine at Shanghai University. Her research interests are mainly focused on the development of functionalized micro- and nanobiomaterials for biomedical applications.

Jingchao Li received his Ph.D. degree in Materials Science and Engineering from the University of Tsukuba (Japan) in 2017. Then he worked as a Postdoctoral Research Fellow in the School of Chemical and Biomedical Engineering, Nanyang Technological University. His current research focuses on the development of advanced nanomaterials for cancer theranostics.

Shaojun Peng is now an associate research fellow at Zhuhai Institute of Translational Medicine, Zhuhai hospital affiliated with Jinan University. He received his B.S. degree in Sichuan University in 2011 and then joined University of Chinese Academy of Sciences for a Master degree in 2014. He obtained the Doctoral degree at Fudan University in 2018. His current research subjects are focused on the cancer phototherapy and zwitterionic drug delivery systems.

Xiaolin Wang is a director of Shanghai Institute of Medical Imaging, Fudan university, and professor of department of Interventional Radiology, Zhongshan Hospital. Prof. Wang has published more than 20 SCI papers on important international journals. His research interests lie in the development of new diagnosis and treatment for various malignant tumors.

Rong Cai is an assistant professor at the National Center for Nanoscience and Technology (NCNST), Chinese Academy of Sciences (CAS). She received her B.S. degree in materials science and engineering in 2008 from Beijing University of Chemical Technology, China, and her Ph.D. in materials science and engineering in 2015 from the University of Tsukuba and National Center for Materials Science (NIMS), Japan. Her research interests are mainly focused on the understanding of biological effects of nanomaterials and nanosafety for nanobiomedical applications.

¹: H. Sun and Q. Zhang contributed equally to this work.

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Nano Today

ReviewNear-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy

Highlights

Abstract

Graphical Abstract

Introduction

Section snippets

Design of NIR photoactivated nanomedicines

Synergistic therapy between PTT and chemotherapy

Synergetic therapy between PTT and nanoenzymes

PTT-synergized gene therapy

Synergistic therapy between PTT and PDT

Synergistic therapy of PTT and CDT

PTT-synergized thermodynamic therapy (TDT)

PTT-synergized immunotherapy

PTT-synergized multimodal therapies

Conclusion and outlook

CRediT authorship contribution statement

Declaration of Competing Interest

Acknowledgments

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Adv. Drug Deliv. Rev.

J. Control. Release

Adv. Drug Deliv. Rev.

Biotechnol. Adv.

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Biomaterials

Biomaterials

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Adv. Drug Deliv. Rev.

Cancer Treat. Rev.

Acta Biomater.

Acta Biomater.

Biomaterials

Biomaterials

Acta Biomater.

Biomaterials

Survey of clinical translation of cancer nanomedicines—lessons learned from successes and failures

Acc. Chem. Res.

Cancer nanomedicine: progress, challenges and opportunities

Nat. Rev. Cancer

Immunomodulating nanomedicine for cancer therapy

Nano Lett.

Improving cancer immunotherapy through nanotechnology

Nat. Rev. Cancer

Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

Nat. Rev. Clin. Oncol.

Stimuli-responsive nanomedicines for overcoming cancer multidrug resistance

Theranostics

Stimulus-responsive nanomedicines for disease diagnosis and treatment

IJMS

Stimuli-responsive nanocarriers for drug delivery

Nat. Mater.

Redox-sensitive nanoscale coordination polymers for drug delivery and cancer theranostics

ACS Appl. Mater. Interfaces

Development of endogenous enzyme-responsive nanomaterials for theranostics

Chem. Soc. Rev.

Functional DNA molecules enable selective and stimuli-responsive nanoparticles for biomedical applications

Acc. Chem. Res.

Design and functionalization of the NIR-responsive photothermal semiconductor nanomaterials for cancer theranostics

Acc. Chem. Res.

Self-assembled peptide- and protein-based nanomaterials for antitumor photodynamic and photothermal therapy

Adv. Mater.

Two‐dimensional nanomaterials for photothermal therapy

Angew. Chem. Int. Ed.

Photothermal therapy and photoacoustic imagingviananotheranostics in fighting cancer

Chem. Soc. Rev.

Adv. Sci.

Near‐infrared‐II molecular dyes for cancer imaging and surgery

Adv. Mater.

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Adv. Mater.

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Review
Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy