Nanotechnology based gas delivery system: a "green" strategy for cancer diagnosis and treatment

Abstract

Gas therapy, a burgeoning clinical treatment modality, has garnered widespread attention to treat a variety of pathologies in recent years. The advent of nanoscale gas drug therapy represents a novel therapeutic strategy, particularly demonstrating immense potential in the realm of oncology. This comprehensive review navigates the landscape of gases endowed with anti-cancer properties, including hydrogen (H₂), carbon monoxide (CO), carbon dioxide (CO₂), nitric oxide (NO), oxygen (O₂), sulfur dioxide (SO₂), hydrogen sulfide (H₂S), ozone (O₃), and heavier gases. The selection of optimal delivery vectors is also scrutinized in this review to ensure the efficacy of gaseous agents. The paper highlights the importance of engineering stimulus-responsive delivery systems that enable precise and targeted gas release, thereby augmenting the therapeutic efficiency of gas therapy. Additionally, the review examines the synergistic potential of integrating gas therapy with conventional treatments such as starvation therapy, ultrasound (US) therapy, chemotherapy, radiotherapy (RT), and photodynamic therapy (PDT). It also discusses the burgeoning role of advanced multimodal and US imaging in enhancing the precision of gas therapy applications. The insights presented are pivotal in the strategic development of nanomedicine platforms designed for the site-specific delivery of therapeutic gases, heralding a new era in cancer therapeutics.

Keywords: Cancer treatment; Controlled release; Delivery systems; Gas therapy; Nanomedicine.

Figure 1

The history of gas therapy and the molecular mechanisms of major gases. (A) Advancements and key milestones in gas therapy. (B) Biological changes in cancer cells adapt to hypoxia. Adapted with permission from , copyright 2023 Zhou Chen et al. (C) NO effects in the context of cancer. Adapted with permission from , copyright 2023 Elsevier. (D) CO effects in the context of cancer. Adapted with permission from , copyright 2023 Elsevier. (E) H₂S effects in the context of cancer. Adapted with permission from , copyright 2023 Elsevier.

Figure 2

Gas delivery system using PFC, MOF and silica-based nanoplatform as gas carriers. (A) An oxygen carrier (PSPP-Au₉₈₀-D using PFC). Adapted with permission from , copyright 2022 Wiley-VCH. (B) A copper-based MOF loaded with cisplatin-arginine (Pt-Arg) prodrug. Adapted with permission from , copyright 2022 Sijie Wang et al. (C) A silica-based nanoplatform (Cu₂O/BNN6@MSN-Dex). Adapted with permission from , copyright 2023 Elsevier.

Figure 3

Gas delivery system using 2D material, photosynthetic cyanobacteria, and PLGA as gas carriers. (A) A 2D material-based gas delivery nanoplatforms (Arg@VMT@PDA-PEG NSs). Adapted with permission from , copyright 2023 Elsevier. (B) Another 2D material-based gas delivery nanoplatforms (Au⁰-Por nanosheets). Reproduced with permission from , copyright 2023 Wiley-VCH. (C) A gas delivery system using photosynthetic cyanobacteria. Reproduced with permission from , copyright 2022 Weili Wang et al. (D) A gas delivery system using PLGA (GW/MnCO@PLGA). Reproduced with permission from , copyright 2022 Bin Liu et al.

Figure 4

Exogenous stimuli-responsive gas delivery systems. (A) A NIR-responsive nanoplatform (CuS@SiO₂-L-Arg@PCM-Ce6). Adapted with permission from , copyright 2021 Wiley-VCH. (B) A NIR-responsive nanoplatform (C/B@M NPs). Adapted with permission from , copyright 2024 Elsevier. (C) An US-responsive nanoplatform (APBN). Reproduced with permission from , copyright 2024 Xiahui Lin et al. (D) An US-responsive necroptosis-inducible NBs. Adapted with permission from , copyright 2020 Wiley-VCH. (E) An X-ray-responsive gas delivery system (O₃/O₂_PFD@Liposome). Adapted with permission from , copyright 2022 Elsevier. (F) An X-ray-responsive gas delivery system (Bi-SNO NPs). Reproduced with permission from , copyright 2020 Royal Society of Chemistry. (G) A magnetic-responsive PFH-encapsulated MPs (MDs). Adapted with permission from , copyright 2017 Elsevier.

Figure 5

Endogenous stimuli-responsive gas delivery systems. (A) An acid-responsive SO₂ delivery system (GNRs@PDA-BTS). Reproduced with permission from , copyright 2020 Elsevier. (B) An acid-responsive SO₂ prodrug (GOx/MgAl-SO₃ LDH). Reproduced with permission from , copyright 2021 Wiley-VCH. (C) An acid-responsive H₂ delivery system (MBN@PVP pills). Reproduced with permission from , copyright 2019 Wiley-VCH. (D) H₂O₂-responsive CO-releasing molecules. Adapted with permission from , copyright 2024 Elsevier. (E) A GSH-responsive gas delivery system (Nic-MOF@HA). Reproduced with permission from , copyright 2022 Elsevier. (F) An enzyme-responsive CO prodrug. Reproduced with permission from , copyright 2017 Royal Society of Chemistry.

Figure 6

Application of gas therapy in cancer imaging. (A) A nanoplatform (LDAC NPs) used for PAI/ NIR-II FI dual-mode imaging. Adapted with permission from , copyright 2023 Elsevier. (B) A nanoplatform designed to achieve SDT and ultrasonic imaging (GVs). Reproduced with permission from , copyright 2021 Elsevier. (C) Improved GVs with stable ultrasonic contrast signal. Reproduced with permission from , copyright 2022 Mingjie Wei et al. (D) A nanoplatform designed for ultrasonography imaging, PAI, and MRI (P@TF NPs). Reproduced with permission from , copyright 2023 Wiley-VCH. (E) A nanoplatform AB/DOX@HMPDA-PEG for improving ultrasonic imaging efficacy. Reproduced with permission from , copyright 2021 Elsevier.

Figure 7

Application of gas therapy in cancer treatment synergy with starvation therapy and chemotherapy. (A) Synergistic PDT, SDT and gas therapy (PGI). Reproduced with permission from , copyright 2022 Elsevier. (B) Synergistic cancer starvation therapy, chemotherapy and gas therapy (PGMA Nus). Adapted with permission from , copyright 2022 Elsevier. (C) Synergistic chemotherapy and gas therapy (IGN Lipo). Reproduced with permission from , copyright 2023 Elsevier. (D) Synergistic chemotherapy and gas therapy to overcome MDR (F-L-O@M NPs). Reproduced with permission from , copyright 2023 Elsevier.

Figure 8

Application of gas therapy in cancer treatment synergy with RT, immunotherapy, SDT, PDT and PTT. (A) Synergistic RT and gas therapy (MMV). Adapted with permission from , copyright 2021 Elsevier. (B) Synergistic gas therapy and immunotherapy (R848@Arg). Adapted with permission from , copyright 2024 Xiaqing Wu et al. (C) Synergistic gas therapy and immunotherapy targeting cGAS/STING pathway (ZnS@BSA). Reproduced with permission from , copyright 2021 Wiley-VCH. (D) Synergistic gas therapy and SDT (TL@HPN). Reproduced with permission from , copyright 2022 Xun Guo et al. (E) Synergistic gas therapy and PTT (PBT/NO/Pt). Reproduced with permission from , copyright 2024 Mi Zhang et al.