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Open AccessOpen Access JUSTC Chemistry; Life Sciences 05 July 2023

Polymerized small molecular dyes providing nanoparticles with stable photosensitivity for eradicating cancer cells

  • Hefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Soft Matter Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China

Cite this:
https://doi.org/10.52396/JUSTC-2023-0056
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  • Author Bio:

    Xu Chen is currently pursuing a master’s degree at the University of Science and Technology of China. His research focuses on the application of nanomaterials in the biological field

    Feng Gao received his Ph.D. degree in Materials Science and Engineering from the University of Science and Technology of China (USTC) in 2021. Currently, he is a postdoctoral fellow at USTC. His research focuses on the preparation of biomaterials and their applications in antibacterial and artificial carbon cycling

    Lihua Yang received her Ph.D. degree from the University of Illinois at Urbana Champaign in 2008. She is currently an Associate Professor at the University of Science and Technology of China. Her research mainly focuses on the application of nanomaterials in the biological field

  • Corresponding author: E-mail: gf199203@mail.ustc.edu.cn; E-mail: lhyang@ustc.edu.cn
  • Received Date: 03 April 2023
  • Accepted Date: 30 May 2023
    • Available Online: 05 July 2023
    Abstract

  • Abstract

    To make small molecular photosensitizer-based nanoparticles photostable, we polymerized such photosensitizers via emulsion polymerization, and the resulting nanoparticles exhibited sustained absorption of the excitation wavelength in the near-infrared region, generated stable photothermal and photodynamic effects upon repeated irradiation with an near-infrared laser, and efficiently eradicated cancerous cells even after prior irradiation exposure.

    Graphical abstract

    Synthesis route of CSNP and characterization of its photothermal properties.

    Abstract

    To make small molecular photosensitizer-based nanoparticles photostable, we polymerized such photosensitizers via emulsion polymerization, and the resulting nanoparticles exhibited sustained absorption of the excitation wavelength in the near-infrared region, generated stable photothermal and photodynamic effects upon repeated irradiation with an near-infrared laser, and efficiently eradicated cancerous cells even after prior irradiation exposure.

    • Public Summary

    • In order to improve the loading rate of photosensitizer, small molecular dyes were polymerized into nanoparticles by emulsion polymerization, and their photostability was improved by ensuring high loading efficiency of photosensitizer.
    • The experimental results show that Cypate nanosphere (CyNS) shows good colloidal stability in PBS and continuous absorption of excitation light.
    • After repeated light irradiation, CyNS significantly enhances the stability of photothermal and photodynamic effects, which can lead to a significant improvement in the efficacy of cancer phototherapy with repeated light irradiation.

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    • References(25)
  • [1]
    Yuwen L H, Zhou J J, Zhang Y Q, et al. Aqueous phase preparation of ultrasmall MoSe2 nanodots for efficient photothermal therapy of cancer cells. Nanoscale, 2016, 8 (5): 2720–2726. doi: 10.1039/C5NR08166A
    [2]
    Huang P, Lin J, Li W W, et al. Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy. Angew. Chem. Int. Edit., 2013, 52 (52): 13958–13964. doi: 10.1002/anie.201308986
    [3]
    Tian B, Wang C, Zhang S, et al. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano, 2011, 5 (9): 7000–7009. doi: 10.1021/nn201560b
    [4]
    Shi S G, Zhu X L, Zhao Z X, et al. Photothermally enhanced photodynamic therapy based on mesoporous Pd@Ag@mSiO2 nanocarriers. J. Mater. Chem. B., 2013, 1 (8): 1133–1141. doi: 10.1039/c2tb00376g
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    Huang X H, El-Sayed I H, Qian W, et al. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc., 2006, 128 (6): 2115–2120. doi: 10.1021/ja057254a
    [6]
    Nolsøe C P, S. Torp-Pedersen S, Burcharth F, et al. Interstitial hyperthermia of colorectal liver metastases with a US-guided Nd-YAG laser with a diffuser tip: A pilot clinical study. Radiology, 1993, 187 (2): 333–337. doi: 10.1148/radiology.187.2.8475269
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    Dolmans D E J G J, Fukumura D, Jain R K. Photodynamic therapy for cancer. Nat. Rev. Cancer, 2003, 3 (5): 380–387. doi: 10.1038/nrc1071
    [8]
    Piao J G, Wang L M, Gao F, et al. Erythrocyte membrane is an alternative coating to polyethylene glycol for prolonging the circulation lifetime of gold nanocages for photothermal therapy. ACS Nano, 2014, 8 (10): 10414–10425. doi: 10.1021/nn503779d
    [9]
    Chen H C, Tian J W, He W J, et al. H2O2-activatable and O2-evolving nanoparticles for highly efficient and selective photodynamic therapy against hypoxic tumor cells. J. Am. Chem. Soc., 2015, 137 (4): 1539–1547. doi: 10.1021/ja511420n
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    Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat. Med., 2003, 9 (1): 123–128. doi: 10.1038/nm0103-123
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    Ma Z Y, Yang M K, Foda M F, et al. Polarization of tumor-associated macrophages promoted by vitamin C-loaded liposomes for cancer immunotherapy. ACS Nano, 2022, 26 (10): 17389–17401. doi: 10.1021/acsnano.2c08446
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    Zheng M B, Yue C X, Ma Y F, et al. Single-step assembly of DOX/ICG loaded lipid–polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano, 2013, 7 (3): 2056–2067. doi: 10.1021/nn400334y
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    Li Y L, Deng Y B, Tian X, et al. Multipronged design of light-triggered nanoparticles to overcome cisplatin resistance for efficient ablation of resistant tumor. ACS Nano, 2015, 9 (10): 9626–9637. doi: 10.1021/acsnano.5b05097
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    1.  Schematic illustration of the preparation of Cypate nanospheres (CyNSs), which are obtained by polymerizing the Cypate-HEA monomer, in which one carboxyl group of a Cypate molecule is esterified with 2-hydroxyethyl acrylate (HEA) via an emulsion polymerization process.

    Figure  1.  (a) Transmission electron microscopy image of CyNS. Scale bar = 500 nm. (b) The average zeta potential of CyNS in aqueous solution. (c) The average hydrodynamic diameters of CyNS in 1×PBS over a span of 5 d. Data points are reported as the mean ± standard deviation. (d) Normalized absorbance ratios of CyNS (PS content of 10.0 μg/mL, 0.5 mL) at different time points during irradiation with an 808-nm laser at 1.0 W/cm2 for 15 min in total, with those of free Cypate included for comparison.

    Figure  2.  (a) Cumulative heat generated by the dispersion of CyNS in PBS (PS content of 10 μg/mL, 400 μL) at different time points during the 1st, 2nd, 3rd, 4th, 5th, and 6th irradiation treatments (with an 808-nm laser at 1.0 W/cm2 for 10 min), with those of free Cypate in DMF included for comparison. \\: indicates natural cooling for 12 h. (b) Thermographs of mice injected with CyNS, free Cypate, or PBS during a 10-min irradiation (with an 808-nm laser at 1.0 W/cm2) immediately after injection. Mice assayed similarly but injected with PBS only are included as a reference. (c) Plots of temperature change at the tumor site as a function of irradiation time based on thermographs. Data points are reported as the mean ± standard deviation (n=3). ** indicates p< 0.01. (d) Fluorescence emission spectra of dichlorofluorescein hydrolysate (DCFH) in dispersions of CyNS in PBS and Cypate in methanol after the 1st, 2nd, 3rd, and 4th treatments. \\: natural cooling for 2 min.

    Figure  3.  In vitro cell viability assays using free Cy/pretreated Cy and CyNS/pretreated CyNS incubated with HeLa cells for 24 h with 10 min of irradiation (808 nm, 1.0 W/cm2). Controls are culture medium irradiated similarly with an 808-nm laser at 1.0 W/cm2. Data points are reported as the mean ± standard deviation. ** indicates p < 0.01.

    [1]
    Yuwen L H, Zhou J J, Zhang Y Q, et al. Aqueous phase preparation of ultrasmall MoSe2 nanodots for efficient photothermal therapy of cancer cells. Nanoscale, 2016, 8 (5): 2720–2726. doi: 10.1039/C5NR08166A
    [2]
    Huang P, Lin J, Li W W, et al. Biodegradable gold nanovesicles with an ultrastrong plasmonic coupling effect for photoacoustic imaging and photothermal therapy. Angew. Chem. Int. Edit., 2013, 52 (52): 13958–13964. doi: 10.1002/anie.201308986
    [3]
    Tian B, Wang C, Zhang S, et al. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano, 2011, 5 (9): 7000–7009. doi: 10.1021/nn201560b
    [4]
    Shi S G, Zhu X L, Zhao Z X, et al. Photothermally enhanced photodynamic therapy based on mesoporous Pd@Ag@mSiO2 nanocarriers. J. Mater. Chem. B., 2013, 1 (8): 1133–1141. doi: 10.1039/c2tb00376g
    [5]
    Huang X H, El-Sayed I H, Qian W, et al. Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J. Am. Chem. Soc., 2006, 128 (6): 2115–2120. doi: 10.1021/ja057254a
    [6]
    Nolsøe C P, S. Torp-Pedersen S, Burcharth F, et al. Interstitial hyperthermia of colorectal liver metastases with a US-guided Nd-YAG laser with a diffuser tip: A pilot clinical study. Radiology, 1993, 187 (2): 333–337. doi: 10.1148/radiology.187.2.8475269
    [7]
    Dolmans D E J G J, Fukumura D, Jain R K. Photodynamic therapy for cancer. Nat. Rev. Cancer, 2003, 3 (5): 380–387. doi: 10.1038/nrc1071
    [8]
    Piao J G, Wang L M, Gao F, et al. Erythrocyte membrane is an alternative coating to polyethylene glycol for prolonging the circulation lifetime of gold nanocages for photothermal therapy. ACS Nano, 2014, 8 (10): 10414–10425. doi: 10.1021/nn503779d
    [9]
    Chen H C, Tian J W, He W J, et al. H2O2-activatable and O2-evolving nanoparticles for highly efficient and selective photodynamic therapy against hypoxic tumor cells. J. Am. Chem. Soc., 2015, 137 (4): 1539–1547. doi: 10.1021/ja511420n
    [10]
    Weissleder R. A clearer vision for in vivo imaging. Nat. Biotechnol., 2001, 19 (4): 316–317. doi: 10.1038/86684
    [11]
    Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat. Med., 2003, 9 (1): 123–128. doi: 10.1038/nm0103-123
    [12]
    Ma Z Y, Yang M K, Foda M F, et al. Polarization of tumor-associated macrophages promoted by vitamin C-loaded liposomes for cancer immunotherapy. ACS Nano, 2022, 26 (10): 17389–17401. doi: 10.1021/acsnano.2c08446
    [13]
    Wu L, Fang S T, Shi S, et al. Hybrid polypeptide micelles loading indocyanine green for tumor imaging and photothermal effect study. Biomacromolecules, 2013, 14 (9): 3027–3033. doi: 10.1021/bm400839b
    [14]
    Zheng X H, Xing D, Zhou F F, et al. Indocyanine green-containing nanostructure as near infrared dual-functional targeting probes for optical imaging and photothermal therapy. Mol. Pharmaceut., 2011, 8 (2): 447–456. doi: 10.1021/mp100301t
    [15]
    Yu J, Javier D, Yaseen M A, et al. Self-assembly synthesis, tumor cell targeting, and photothermal capabilities of antibody-coated indocyanine green nanocapsules. J. Am. Chem. Soc., 2010, 132 (6): 1929–1938. doi: 10.1021/ja908139y
    [16]
    Yang H, Mao H J, Wan Z H, et al. Micelles assembled with carbocyanine dyes for theranostic near-infrared fluorescent cancer imaging and photothermal therapy. Biomaterials, 2013, 34 (36): 9124–9133. doi: 10.1016/j.biomaterials.2013.08.022
    [17]
    Wang Y, Yang T, Ke H T, et al. Smart albumin-biomineralized nanocomposites for multimodal imaging and photothermal tumor ablation. Adv. Mater., 2015, 27 (26): 3874–3882. doi: 10.1002/adma.201500229
    [18]
    Han Y, Li J J, Zan M H, et al. Redox-responsive core cross-linked micelles based on cypate and cisplatin prodrugs-conjugated block copolymers for synergistic photothermal–chemotherapy of cancer. Polym. Chem., 2014, 5 (11): 3707–3718. doi: 10.1039/C4PY00064A
    [19]
    Zheng M B, Yue C X, Ma Y F, et al. Single-step assembly of DOX/ICG loaded lipid–polymer nanoparticles for highly effective chemo-photothermal combination therapy. ACS Nano, 2013, 7 (3): 2056–2067. doi: 10.1021/nn400334y
    [20]
    Li Y L, Deng Y B, Tian X, et al. Multipronged design of light-triggered nanoparticles to overcome cisplatin resistance for efficient ablation of resistant tumor. ACS Nano, 2015, 9 (10): 9626–9637. doi: 10.1021/acsnano.5b05097
    [21]
    Bugaj J E, Achilefu S I, Dorshow R B, et al. Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. J. Biomed. Opt., 2001, 6 (2): 122–133. doi: 10.1117/1.1352748
    [22]
    Ye Y P, Bloch S, Kao J, et al. Multivalent carbocyanine molecular probes: Synthesis and applications. Bioconjugate Chem., 2005, 16 (1): 51–61. doi: 10.1021/bc049790i
    [23]
    Bourré L, Thibaut S, Briffaud A, et al. Indirect detection of photosensitizer ex vivo. J. Photochem. Photobiol. B, 2002, 67 (1): 23–31. doi: 10.1016/S1011-1344(02)00279-8
    [24]
    Yuan Y, Min Y, Hu Q, et al. NIR photoregulated chemo- and photodynamic cancer therapy based on conjugated polyelectrolyte–drug conjugate encapsulated upconversion nanoparticles. Nanoscale, 2014, 6 (19): 11259–11272. doi: 10.1039/C4NR03302G
    [25]
    Knop K, Hoogenboom R, Fischer D, et al. Poly(ethylene glycol) in drug delivery: Pros and cons as well as potential alternatives. Angew. Chem. Int. Ed., 2010, 49 (36): 6288–6308. doi: 10.1002/anie.200902672
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