Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 22:24:100926.
doi: 10.1016/j.mtbio.2023.100926. eCollection 2024 Feb.

Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy

Xinxin Xie  1 , Jinxia Zhang  1 , Yuan Wang  1 , Wanrui Shi  1 , Rui Tang  1 , Qingshuang Tang  1 , Suhui Sun  1 , Ruiqi Wu  1 , Shuyu Xu  1 , Mengxin Wang  1 , Xiaolong Liang  1 , Ligang Cui  1
Affiliations
Review

Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy

Xinxin Xie et al. Mater Today Bio. .

Abstract

Immunotherapy as a milestone in cancer treatment has made great strides in the past decade, but it is still limited by low immune response rates and immune-related adverse events. Utilizing bioeffects of ultrasound to enhance tumor immunotherapy has attracted more and more attention, including sonothermal, sonomechanical, sonodynamic and sonopiezoelectric immunotherapy. Moreover, the emergence of nanomaterials has further improved the efficacy of ultrasound mediated immunotherapy. However, most of the summaries in this field are about a single aspect of the biological effects of ultrasound, which is not comprehensive and complete currently. This review proposes the recent progress of nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy. The concept of immunotherapy and the application of bioeffects of ultrasound in cancer immunotherapy are initially introduced. Then, according to different bioeffects of ultrasound, the representative paradigms of nanomaterial augmented sono-immunotherapy are described, and their mechanisms are discussed. Finally, the challenges and application prospects of nanomaterial augmented ultrasound mediated cancer immunotherapy are discussed in depth, hoping to pave the way for cancer immunotherapy and promote the clinical translation of ultrasound mediated cancer immunotherapy through the reasonable combination of nanomaterials augmented ultrasonic bioeffects.

Keywords: Cancer immunotherapy; Nanomaterial; Sonodynamic; Sonomechanical; Sonopiezoelectric; Sonothermal; Ultrasound.

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Schematic illustration of nanomaterials augmented ultrasonic bioeffects in cancer immunotherapy. Created with BioRender.com.
Fig. 2
Fig. 2
Schematic diagram of biological effects of ultrasound. Reprinted with permission from Ref. [85]. Copyright 2021, MDPI.
Fig. 3
Fig. 3
The thermal effect of HIFU enhances immunotherapy. a) Schematic illustration for the construction of PLD@NEs and its mechanism to enhance immunotherapy. Reproduced with permission from Ref. [110]. Copyright 2022, Springer Nature. b) Schematic illustration for the construction of M@P–SOP and its mechanism to enhance immunotherapy. Reproduced with permission from Ref. [111]. Copyright 2023, BMJ Publishing Group Ltd.
Fig. 4
Fig. 4
Illustration of UTMD-mediated gene transfection and drug delivery to enhance immunotherapy. a) Schematic illustration of mechanism of UTMD-mediated gene transfection. Reprinted with permission from Ref. [130]. Copyright 2020, PNAS. b) Schematic illustration of UTMD-mediated drug delivery to enhance immunotherapy. Exhibited the preparation process of RD@MBs and mechanism of in vivo antitumor immune response induced by RD@MB combined with αPD-L1. Reprinted with permission from Ref. [132]. Copyright 2023, Springer Nature. c) Schematic illustration of UTMD-mediated drug delivery to enhance immunotherapy and the fabrication of immunogenic αPCF MBs and US mediated micro−nano conversion. Reprinted with permission from Ref. [133]. Copyright 2022, American Chemical Society.
Fig. 5
Fig. 5
Illustration of SDT synergistically enhances the efficacy of ICB therapy. a) Schematic illustration of TiSe2 nanosheets-mediated SDT binded with αPD-L1 to enhance immunotherapy, b) primary tumor growth, (c) distant tumor growth and survival rates for mice bearing metastatic Pan02-luci tumors after different treatments. Reprinted with permission from Ref. [143]. Copyright 2022, Springer Nature. e) Schematic of the synthesis of the SPNAb and its mechanism for synergistic enhancement of αCTLA-4. f) tumor growth, g) survival rates and h) numbers of metastatic nodules per lung for mice bearing 4T1 tumors after different treatments. Reprinted with permission from Ref. [146]. Copyright 2022, Wiley-VCH.
Fig. 6
Fig. 6
Illustration of SDT synergistically enhances the efficacy of immune system modulators by TLRs and STING-agonists. a) Scheme of antitumor immune responses induced by combined SDT with TLRs R837 and αPD-L1. Reprinted with permission from Ref. [13]. Copyright 2022, Springer Nature. b) Scheme of mechanism for iSDT enhanced by HMME@BiL with STING-agonists. Reprinted with permission from Ref. [148]. Copyright 2022, Wiley-VCH. c) Synthesis of PSPA and its mechanisms to synergistically enhance immunotherapy. Reprinted with permission from Ref. [149]. Copyright 2023, Wiley-VCH.
Fig. 7
Fig. 7
Illustration of SDT synergistically enhances immunotherapy by activating STING pathway through Mn2+. a) The mechanism diagram of PIMS NPs promoted DCs maturation and sensitized ICB therapy. b) Tumor volume growth curves for distant tumors, c) mature DCs in DLNs, d) memory T cells in spleen and e) H&E staining images of lung metastasis in 4T1 bearing mice after different treatments. Reprinted with permission from Ref. [151]. Copyright 2022, Elsevier.
Fig. 8
Fig. 8
Illustration of dual-cascade activatable nanopotentiator (NPMCA) for enhancing immunotherapy. a) Scheme of NPMCA Synthesis and its antitumor immune mechanism. Immunofluorescence staining of b) CRT and c) HMGB1 in primary tumors covered by chicken breast tissue. d) Flow cytometry analysis of DCs in LNs of mice after different treatments. e) Relative fluorescence intensity of HMGB1 and f) relative ATP levels in primary tumors covered by chicken breast tissue after different treatments. g) Number of CD8+ T cells in distant tumors after different treatments. Reprinted with permission from Ref. [152]. Copyright 2023, Wiley-VCH.
Fig. 9
Fig. 9
Illustration of enhancing immunotherapy by utilizing tumor physiological environment in coordination with SDT. a) Scheme of the formation of SPNTi and its antitumor immunotherapy mechanism. b) Intratumoral ATP levels, Tumor c) CRT and d) HMGB1 immunofluorescence staining images in mice under different treatments. Reprinted with permission from Ref. [154]. Copyright 2023, Wiley-VCH. e) Scheme of the formation of PgP@Fe–COF NPs and its antitumor immunotherapy mechanism. f) Treatment regimen of the combination therapy. g) The flow cytometry results of CD4+ and CD8+ T cells in the tumors. The quantitative analysis of h) CD8+ T cells and i) CD8+ IFN-γ+ T cells in the tumors. The relative change of j) IL-6 and k) IL-10 in tumors. Reprinted with permission from Ref. [155]. Copyright 2022, Wiley-VCH.
Fig. 10
Fig. 10
Illustration of enhancing immunotherapy by altering tumor immunosuppressive cells. a) Scheme of reshaping macrophages in coordination with SDT through MPIRx to enhance immunotherapy. Reprinted with permission from Ref. [156]. Copyright 2023, Wiley-VCH. b) Scheme of inhibiting TGF-β by NCG cooperated with SDT to enhance immunotherapy. Reprinted with permission from Ref. [157]. Copyright 2023, Elsevier. c) Scheme of depleting M2 macrophages targeted by M-H@lip-ZA along with SDT to enhance immunotherapy. d) M2-like TAMs and e) PD-L1 expression on M2-Like TAMs after different treatments. The level of f) IL-10, g) TGF-β, h) IL-12 and i) IFN-γ in serum from mice receive treatments. Reprinted with permission from Ref. [158]. Copyright 2023, Elsevier.
Fig. 11
Fig. 11
Illustration of enhancing immunotherapy by enhanced apoptosis in coordination with SDT. a) Scheme of PMPS synthesis route and its antitumor immune mechanism in vivo. The flow-cytometry results of b) CD8+ T cell and c) NK cells in tumors. Reprinted with permission from Ref. [161]. Copyright 2022, Springer Nature.
Fig. 12
Fig. 12
Illustration of enhancing immunotherapy by necroptosis in coordination with SDT. a) Scheme of necroptosis-inducible NBs for antitumor immune response. Reprinted with permission from Ref. [162]. Copyright 2020, Wiley-VCH. b) Scheme of iCRET NPs led to enhanced immune responses by CRET. Reprinted with permission from Ref. [163]. Copyright 2022, Elsevier.
Fig. 13
Fig. 13
Illustration of enhancing immunotherapy by pyroptosis in coordination with SDT. Scheme of iSDT induced by the nanostimulator LPM. Reprinted with permission from Ref. [164]. Copyright 2023, Ivyspring.
Fig. 14
Fig. 14
Illustration of enhancing immunotherapy by autophagy in coordination with SDT. a) Scheme of the preparation and antitumor mechanism of HAL/3 MA@X-MP. b) CLSM and c) Bio-TEM images of autophagosomes in 4T1 cells after different treatments. Reprinted with permission from Ref. [166]. Copyright 2023, American Chemical Society.
Fig. 15
Fig. 15
Illustration of enhancing immunotherapy by Ferroptosis in coordination with SDT. a) Scheme of CS-ID@NMs as multi-functional motors achieved efficient mucus-traversing ability, deep tumor penetration and potentiation of antitumor immunity. b) Immunofluorescence staining of CD4+ CD8+ T cells, Foxp3+ cells and quantitative analysis of c) CD4+ CD8+ T cells and d) Foxp3+ cells in the tumors after various treatments. Reprinted with permission from Ref. [167]. Copyright 2022, Wiley-VCH.
Fig. 16
Fig. 16
Illustration of enhancing immunotherapy by gas therapy in coordination with SDT. a) Scheme of TiSx NSs as bioreactors to enhance antitumor immunotherapy. Flow cytometry results of b) CD4+ T cells, c) M1 macrophages in tumors after treated with TiSx NSs. d) Flow cytometry results of mature DCs in lymph nodes after treated with TiSx NSs. e) Digital photographs of lung metastases in different groups. Reprinted with permission from Ref. [169]. Copyright 2022, Wiley-VCH.
Fig. 17
Fig. 17
Illustration of enhancing immunotherapy by all-in-one strategy. a) Mechanism of CPDA@PFH regulated by Focused Acoustic Vortex to enhance antitumor immunotherapy. Flow cytometry plots of b) CD4+ Foxp3+ T cells in distant tumor and c) CD3e + CD8+ T cells in primary tumor 7 days after various treatments. The level of d) TNF-α and e) IFN-γ detected by ELISA 7 days after various treatments. Reprinted with permission from Ref. [172]. Copyright 2022, American Chemical Society.
Fig. 18
Fig. 18
Illustration of enhancing immunotherapy by SPT. a) illustration of the mechanism of sonopiezoelectric therapy. Reproduced with permission from Ref. [176]. Copyright 2021, American Chemical Society. b) Piezoelectric catalysis for enhanced immunotherapy. Schematic depiction of M@BTO mediated iSPT. Reproduced with permission from Ref. [183]. Copyright 2023, Wiley-VCH.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Wang Ping, Sun Suhui, Ma Huide, Sun Sujuan, Zhao Duo, Wang Shumin, Liang Xiaolong. Treating tumors with minimally invasive therapy: a review. Mater Sci Eng C Mater Biol Appl. 2022;108 https://doi:10.1016/j.msec.2019.110198 - DOI - PubMed
    1. Jiang Ouyang, Xie Angel, Zhou Jun, Liu Runcong, Wang Liqiang, Liu Haijun, Kong Na, Tao Wei. Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging. Chem. Soc. Rev. 2022;51(12):4996–5041. https://doi:10.1039/d1cs01148k - DOI - PubMed
    1. Zhang Lin, Zhou Wei, Velculescu Victor E., Scott E., Kern Ralph H. Hruban, Hamilton Stanley R., Kinzler Kenneth W. Gene expression profiles in normal and cancer cells. Science. 1997;276(5316):1268–1272. https://doi:10.1126/science.276.5316.1268 - DOI - PubMed
    1. Yang Bo, Wang Hua. Biomaterial-based in situ cancer vaccines. Adv. Mater. 2023;17 https://doi:10.1002/adma.202210452 - DOI - PMC - PubMed
    1. Darvin Pramod, Toor Salman M., Nair Varun Sasidharan, Elkord Eyad. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp. Mol. Med. 2018;50(12):1–11. https://doi:10.1038/s12276-018-0191-1 - DOI - PMC - PubMed

LinkOut - more resources

-