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Multi-target responsive nanoprobe with cellular-level accuracy for spatiotemporally selective photodynamic therapy

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Abstract

Photodynamic therapy is known for its non-invasiveness to significantly reduce undesired side effects on patients. However, the infiltration and invasiveness of tumor growth are still beyond the specificity of traditional light-controlled photodynamic therapy (PDT), which lacks cellular-level accuracy to tumor cells, possibly leading to “off-target” damage to healthy tissues such as the skin or immune cells infiltrated. Here, upconversion nanoparticles (UCNPs) were co-encapsulated with manganese dioxide (MnO2) by amphiphilic polymers poly(styrene-co-methyl acrylate) (PSMA) and further coated with photosensitizer (riboflavin)-loaded mesoporous silica (C@S/V). The C@S/V nanoprobes exhibited shielded upconversion luminescence in normal conditions (pH 7.4, no hydroperoxide (H2O2)) under 980-nm irradiation and thus minimal reactive oxygen production from riboflavin. However, the excess H2O2 (1 mM) and acidic environment (pH 5.5) could decompose the MnO2 within the C@S/V, resulting in remarkable enhancement of upconversion luminescence and a favorable hypoxia-relieving condition for PDT, providing a spatiotemporal signal for therapy initiation. The C@S/V nanoprobes were applied to the co-culture of normal cells (HEK293) and pancreatic cancer cells (Panc02) and performed a selective killing on Panc02 under the 980-nm irradiation. By using the “double-safety” strategy, a responsive C@S/V nanoprobe was designed by the selective activation of acidic and H2O2-rich conditions and 980-nm irradiation for spatiotemporally selective photodynamic therapy with cellular-level accuracy.

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Data Availability

The data in this work are available from the corresponding author upon reasonable request.

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Funding

The work was supported by the grants from National Natural Science Foundation of China (22074028), Guangdong Basic and Applied Basic Research Foundation (2023B1515020056, 2022A1515111012), Guangzhou Science and Technology Project (2023B03J1228), the Fundamental Research Funds for the Central Universities of China (21622106), and China Postdoctoral Science Foundation (2023M731314).

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Author notes

  1. Huimin Fu and Qi Lu contributed equally.

Authors and Affiliations

  1. School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230009, People’s Republic of China

    Huimin Fu, Pingping Wan & Huajian Xu

  2. Department of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China

    Huimin Fu, Qi Lu, Yi Zhang, Cheng Liao, Yaru Sun & Qingsong Mei

  3. Department of Stomatology, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China

    Yun Deng & Wangxiang Yan

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  1. Huimin Fu
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  3. Yi Zhang
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Contributions

H. F. and Q. L. contributed equally.

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Correspondence to Yi Zhang, Huajian Xu, Wangxiang Yan or Qingsong Mei.

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Supplementary Information

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604_2023_6022_MOESM1_ESM.docx

Supplementary file1 (DOCX 1100 KB) The Supporting Information is available free of charge on the ACS Publications website. Detailed experiment section; TEM figures of C@S with different ratio of PSMA and TEOS (Figure S1); TEM figures of C@S/V (Figure S2); The FTIR spectra of C@S and C@S/V (Figure S3); The UV-Vis absorbance of riboflavin solutions with different concentrations (Figure S4); The linear fitting curve of riboflavin concentration and UV-Vis absorbance (Figure S5); The upconversion luminescence spectra of C@S and C@S/V under the 980 nm excitation (Figure S6); The luminescence recovery in different timepoints of C@S/V (Figure S7 and Figure S8); TEM figures of UCNP/MnO2 nanoclusters after reaction in acidic H2O2 solutions (Figure S9); The singlet oxygen production of C@S/V under different conditions (Figure S10 and Figure S11) (PDF).

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Fu, H., Lu, Q., Zhang, Y. et al. Multi-target responsive nanoprobe with cellular-level accuracy for spatiotemporally selective photodynamic therapy. Microchim Acta 190, 448 (2023). https://doi.org/10.1007/s00604-023-06022-4

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