Theranostic applications of selenium nanomedicines against lung cancer

Abstract

The incidence and mortality rates of lung cancer are among the highest in the world. Traditional treatment methods include surgery, chemotherapy, and radiotherapy. Although rapid progress has been achieved in the past decade, treatment limitations remain. It is therefore imperative to identify safer and more effective therapeutic methods, and research is currently being conducted to identify more efficient and less harmful drugs. In recent years, the discovery of antitumor drugs based on the essential trace element selenium (Se) has provided good prospects for lung cancer treatments. In particular, compared to inorganic Se (Inorg-Se) and organic Se (Org-Se), Se nanomedicine (Se nanoparticles; SeNPs) shows much higher bioavailability and antioxidant activity and lower toxicity. SeNPs can also be used as a drug delivery carrier to better regulate protein and DNA biosynthesis and protein kinase C activity, thus playing a role in inhibiting cancer cell proliferation. SeNPs can also effectively activate antigen-presenting cells to stimulate cell immunity, exert regulatory effects on innate and regulatory immunity, and enhance lung cancer immunotherapy. This review summarizes the application of Se-based species and materials in lung cancer diagnosis, including fluorescence, MR, CT, photoacoustic imaging and other diagnostic methods, as well as treatments, including direct killing, radiosensitization, chemotherapeutic sensitization, photothermodynamics, and enhanced immunotherapy. In addition, the application prospects and challenges of Se-based drugs in lung cancer are examined, as well as their forecasted future clinical applications and sustainable development.

Keywords: Lung cancer; Nanotechnology; SeNPs; Selenium (Se); Selenium nanomedicines; Theranostic applications.

Fig. 1

Rational design of different SeNPs for cancer treatments. A The internalized Tf-SeNPs trigger the overproduction of intracellular reactive oxygen species (ROS), thereby activating the p53 and mitogen-activated protein kinase (MAPK) pathways and promoting MCF-7 cell apoptosis [47]. Copyright 2013, Elsevier Ltd. B Internalized FA-SeNPs trigger ROS overproduction and induce apoptosis of HePG2 cells by activating the p53 and MAPK pathways [48]. Copyright 2015, Elsevier Ltd. C After the application of GLP − SeNPs, the p53, MAPK and AKT pathways are activated to promote the apoptosis of U87 cells [49]. Copyright 2014, American Chemical Society. D Schematic diagram of SeNP-induced modulation of γδ T cells [50]. Copyright 2019, Elsevier Ltd

Fig. 2

Applications of Se in different respiratory diseases. A Application map of Se diseases. B Comparison of lung cancer mortality after Se supplementation [66]. Copyright 2008, American Medical Association. C Changes in remission rate after Se combined treatment of COPD [56]. Copyright 2010, Blackwell Publishing Ltd. D ESR changes in Se after treatment of pulmonary tuberculosis [60]. Copyright 2007, The Authors. E Changes in the oxygenation index after Se supplementation [63]. Copyright 2014, The Canadian Society of Clinical Chemists. F Three-dimensional description of changes in serum Se, including the effect of bronchoalveolar lavage fluid on the iron-reducing antioxidant capacity (FRAP) of C-reactive protein (CRP) [64]. Copyright 2018, Taylor & Francis

Fig. 3

Different Se forms used in lung cancer treatments. The distinguishing degree and characteristics of the three forms of Se are shown [, –77]. Copyright 2020, Tian, Wei, Zhang and Xu. Copyright 2020, Alkie et al. Copyright 2008, Elsevier B.V. Copyright 2001, Oxford University Press. Copyright 2021 by the authors. Copyright 2020, Chen, Li, Cong, Yu, Zhu, Barba, Marszalek, Puchalski and Cheng. Copyright 2000, Springer-Verlag New York Inc. Copyright 2019, Elsevier B.V

Fig. 4

Morphology of different SeNPs used in cancer treatment and their biological application. A Sodium selenite and quartz tubes were treated with alcohol by heat, laser, and ablation to synthesize rod-shaped SeNPs [117, 118]. Copyright 2002, Elsevier Science B.V. Copyright 2018, IMSS. B Nanotube SeNPs were synthesized with sodium selenite, water, ammonia and ethanol by heating and sonication [–121]. Copyright 2004, American Chemical Society. Copyright 2022, Elsevier B.V. Copyright 2019, Bilek et al. C Synthesis of spherical SeNPs from sodium selenite and potato extract [, , , , –126]. Copyright 2015, Elsevier Inc. Copyright 2012, American Chemical Society. Copyright 2015, Elsevier B.V. Copyright 2006, The Royal Society of Chemistry. Copyright 2003, Regional SOCIETY OF CHEMISTRY. Copyright 2013, Royal Society of Chemistry. Copyright 2018, WILEY‐VCH. Copyright 2018, Royal Society of Chemistry

Fig. 5

Structure of 2D SeNPs for cancer. 2D SeNPs are divided into three categories (MX₂, Se elemental, and Se complex) because their structures and characteristics are different [, –169]. Copyright 2021, American Chemical Society. Copyright 2016, WILEY‐VCH. Copyright 2019, Royal Society of Chemistry. Copyright 2018, American Chemical Society. Copyright 2022, Elsevier B.V. Copyright 2020, The Author(s). Copyright 2017, The Author(s). Copyright 2019, WILEY‐VC. Copyright 2022, Elsevier Ltd. Copyright 2020, The Authors

Fig. 6

SeNPs for cancer diagnosis and imaging. A In vivo imaging of tumor-bearing mice and in vitro FRI of each tissue at different times after Ru-MUA@Se injection [108]. Copyright 2013, Elsevier Ltd. B (CFS@DOX NSs as a diagnostic probe for CT imaging and combined chemotherapy/light therapy [109]. Copyright 2018, American Chemical Society. C BPDC NCs represent a multifunctional and versatile biomedical platform for tumor diagnosis by using FRI [176]. Copyright 2019, Royal Society of Chemistry. D CT image of A549 cells incubated with UCNPS-Bi₂Se₃ nanoheterozygotes [110]. Copyright 2019, Wiley‐VCH. E MR-pegylated MoSe2(Gd³⁺) injected into mice can diagnose cancer by MR [171]. Copyright 2018, Royal Society of Chemistry. F PAA-Ni0.85Se-DOX NPs achieve photothermal-chemical cancer therapy through PAI [177]. Copyright 2017, American Chemical Society

Fig. 7

Direct cancer cell-killing activity of SeNPs. A Nonmetallic NPs encapsulated in combination with RT further induce DNA damage, prevent rapid DNA repair, and lead to more apoptosis [191]. Copyright 2020, The Author(s). C PEG-SeNPs induce apoptosis through mitochondria-mediated pathways [111]. Copyright 2019, The Royal Society of Chemistry. B, D ROS-dependent regulation of HIF-1 activity by PHD2 (chitosan-coated Se/DDP nanoparticles [CSP NPs]) [112]. Copyright 2019, Elsevier B.V

Fig. 8

Synergistic effects of SeNPs and RT. A RT damaged DNA to destroy cell proliferation and gradually induced cell apoptosis over time [196]. Copyright 2019, Springer Nature Limited. B SeNPs kill cells by ROS in conjunction with RT [193]. Copyright 2019, Elsevier Masson SAS

Fig. 9

Synergistic effects of SeNPs and chemotherapy. A SeNPs double deliver MDR1 siRNA and DDP to reverse drug resistance [217]. Copyright 2014, Acta Materialia Inc. B FA@SeNPs and a MAPK-pathway inhibitor for dual targeting of cancer cells [114]. Copyright 2019, American Chemical Society. C Schematic diagram of Se@CMHA-DOX NP-induced apoptosis in cancer cells [218]. Copyright 2017, American Chemical Society. D Se@Trolox blocks cisplatin-induced signaling pathways [124]. Copyright 2013, Royal Society of Chemistry. E SeNPs combined with irinotecan can reduce irinotecan toxicity and treat mice [106]. Copyright 2014, Elsevier Ltd

Fig. 10

Photodynamic and photothermal tumor therapy. A Immunogenic nanotherapeutic agent Au@Se NPs are used for PTT-triggered immunotherapy [239]. Copyright 2020, Elsevier Ltd. B Mechanism of tumor targeting SeNPs by near-infrared laser irradiation [240]. Copyright 2018, Wiley‐VCH

Fig. 11

The immune microenvironment and immune cell status. The immune microenvironment is complex, including tumor cells, immune cells and the secretion of various cytokines, including a number of trace elements. A Prodrug nanodrugs are characterized by prolonged blood circulation time, enhanced tumor accumulation and deeper penetration. Combined with phototherapy, IDO inhibition and PD-L1 blocking, synergistic and effective antitumor immunotherapy can be achieved [256]. Copyright 2020, Elsevier Ltd. B Tumor microenvironments include high infiltration of immune cells, cancer cells, and CAFs/TAFs and increased deposition of ECM protein in the interstitial tissue [257]. Copyright 2018, The Author(s). C Exosomes enhance immunotherapy and reprogram the tumor microenvironment [258]. Copyright 2020, Elsevier Ltd

Fig. 12

SeNPs and NPs can activate NK cell activity in vivo, release factors, and upregulate receptors to play an immunotherapeutic role. A Magnetic nanoparticles encapsulated in tumor cell-derived membranes are used to enhance NK cell-based immunotherapy [260]. Copyright 2020, Elsevier Inc. B NK cells exhibit three types of innate memory and memory-like responses depending on the initial stimulus [261]. Copyright 2021, Elsevier B.V

Fig. 13

SeNPs and NPs can activate T-cell activity in vivo, release factors, and upregulate receptors to play an immunotherapeutic role. A The role of selenoproteins in T-cell biology [268]. Copyright 2021, Springer Nature America, Inc. B Selenium supplementation boosted TFH cells in mice and humans [269]. Copyright 2020, Elsevier Ltd

Fig. 14

SeNPs play an immune role in coordination with other cells. A, C SeNPs and NPs enhance the activity of other cells to promote an antitumor effect [285, 286]. Copyright 2022, Chen, Yang, Fan, Jin, Liao, Li, Liu, Liang, Zhang, Xu and Pi. Copyright 2020, The Pharmaceutical Society of Korea. B SeNPs@LNT promote NK cell secretion of cytokines and macrophage transformation [18]. Copyright 2021, Wiley‐VCH D SeNPs with CIK cells for effective cancer immunotherapy [45]. Copyright 2020, Elsevier Ltd