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. 2020 Feb 24;59(9):3711-3717.
doi: 10.1002/anie.201914434. Epub 2020 Jan 30.

Self-Amplified Photodynamic Therapy through the 1 O2 -Mediated Internalization of Photosensitizers from a Ppa-Bearing Block Copolymer

Zhiyong Liu  1 , Tianye Cao  2   3 , Yudong Xue  1 , Mengting Li  2 , Mengsi Wu  1 , Jonathan W Engle  2 , Qianjun He  3 , Weibo Cai  2 , Minbo Lan  1 , Weian Zhang  1
Affiliations

Self-Amplified Photodynamic Therapy through the 1 O2 -Mediated Internalization of Photosensitizers from a Ppa-Bearing Block Copolymer

Zhiyong Liu et al. Angew Chem Int Ed Engl. .

Abstract

Nanocarriers are employed to deliver photosensitizers for photodynamic therapy (PDT) through the enhanced penetration and retention effect, but disadvantages including the premature leakage and non-selective release of photosensitizers still exist. Herein, we report a 1 O2 -responsive block copolymer (POEGMA-b-P(MAA-co-VSPpaMA) to enhance PDT via the controllable release of photosensitizers. Once nanoparticles formed by the block copolymer have accumulated in a tumor and have been taken up by cancer cells, pyropheophorbide a (Ppa) could be controllably released by singlet oxygen (1 O2 ) generated by light irradiation, enhancing the photosensitization. This was demonstrated by confocal laser scanning microscopy and in vivo fluorescence imaging. The 1 O2 -responsiveness of POEGMA-b-P(MAA-co-VSPpaMA) block copolymer enabled the realization of self-amplified photodynamic therapy by the regulation of Ppa release using NIR illumination. This may provide a new insight into the design of precise PDT.

Keywords: block copolymer; drug delivery; photodynamic therapy; reactive oxygen species; self-amplification.

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Figures

Figure 1.
Figure 1.
Properties of VSP nanoparticles. TEM images of VSP (a) and VSP + light (b). Size distribution of nanoparticles determined by DLS, VSP (c) and VSP + light (d). UV spectrum (e) and fluorescence emission (f) of VSP before and after light irradiation.
Figure 2.
Figure 2.
(a) Ppa release curves in buffer with NIR light irradiation at 24 h for the generation of 1O2. (b) 1O2 generation of nanoparticles determined by DPBF as a detector. (c) Confocal laser scanning microscopy images of cellular internalization of Ppa, VSP and OCP nanoparticles treated with or without 1 min light radiation.
Figure 3.
Figure 3.
In vitro cellular toxicity. (a) Without irradiation. (b) Irradiated with laser for 6 min. (c) Irradiated with laser for 1 min plus 5 min with an interval of 4 h. (d) Contrast of cell viability at 5 µg/mL under different irradiated conditions. (n = 3, mean ± s.d.).
Figure 4.
Figure 4.
(a) In vivo fluorescence imaging and (b) maximum intensity projections of PET imaging of B16F10 tumor-bearing mice after injection OCP and VSP nanoparticles with different time. Quantitative PET imaging-based accumulation kinetics of (c) 64Cu-OCP and (d) 64Cu-VSP nanoparticles in tumor/muscle uptake ratio. Biodistribution of (e) 64Cu-VSP and (f) 64Cu-OCP nanoparticles at 36 h (n = 3).
Figure 5.
Figure 5.
In vivo anti-tumor performance with NIR irradiation. (a) Tumor inhabitation efficiency. (b) Body weight variation. (c) Tumor weight. (d) Photograph of excised tumor. (e) H&E stain of tumor tissue (400 X, scale bar = 150 μm). (n = 4, mean ± s.d., **P < 0.01, ***P < 0.001).
Scheme 1.
Scheme 1.
Schematic illustration of self-amplified near-infrared photodynamic therapy and the mechanism of 1O2-stimuli cleavage.
See this image and copyright information in PMC

References

    1. Dolmans DE, Fukumura D, Jain RK, Nat. Rev. Cancer 2003, 3, 380–387. - PubMed
    1. Lucky SS, Soo KC, Zhang Y, Chem. Rev 2015, 115, 1990–2042. - PubMed
    1. Han Y, Chen Z, Zhao H, Zha Z, Ke W, Wang Y, Ge Z, J. Controlled Release 2018, 284, 15–25; - PubMed
    2. Zheng L, Zhang X, Wang Y, Liu F, Peng J, Zhao X, Yang H, Ma L, Wang B, Chang C, Wei H, Biomacromolecules 2018, 19, 3874–3882; - PubMed
    3. Seah GL, Yu JH, Yang MY, Kim WJ, Kim JH, Park K, Cho JW, Kim JS, Nam YS, J. Controlled Release 2018, 286, 240–253; - PubMed
    4. Saravanakumar G, Lee J, Kim J, Kim WJ, Chem. Commun 2015, 51, 9995–9998. - PubMed
    1. Jin CS, Lovell JF, Chen J, Zheng G, ACS Nano 2013, 7, 2541–2550; - PMC - PubMed
    2. Yu B, Goel S, Ni D, Ellison PA, Siamof CM, Jiang D, Cheng L, Kang L, Yu F, Liu Z, Barnhart TE, He Q, Zhang H, Cai W, Adv. Mater 2018, 30, 1704934; - PMC - PubMed
    3. Jia HR, Zhu YX, Xu KF, Liu X, Wu FG, J. Controlled Release 2018, 286, 103–113; - PubMed
    4. Rahman MM, Ueda M, Hirose T, Ito Y, J. Am. Chem. Soc 2018, 140, 17956–17961; - PubMed
    5. Zhang K, Zhang Y, Meng X, Lu H, Chang H, Dong H, Zhang X, Biomaterials 2018, 185, 301–309; - PubMed
    6. Lovell JF, Jin CS, Huynh E, Jin H, Kim C, Rubinstein JL, Chan WC, Cao W, Wang LV, Zheng G, Nat. Mater 2011, 10, 324–332. - PubMed
    1. Barnard A, Posocco P, Pricl S, Calderon M, Haag R, Hwang ME, Shum VW, Pack DW, Smith DK, J. Am. Chem. Soc 2011, 133, 20288–20300; - PubMed
    2. Lin TY, Li Y, Liu Q, Chen JL, Zhang H, Lac D, Zhang H, Ferrara KW, Wachsmann-Hogiu S, Li T, Airhart S, deVere White R, Lam KS, Pan CX, Biomaterials 2016, 104, 339–351; - PMC - PubMed
    3. Zhou Y, Huang W, Liu J, Zhu X, Yan D, Adv. Mater 2010, 22, 4567–4590; - PubMed
    4. Li Y, Lin TY, Luo Y, Liu Q, Xiao W, Guo W, Lac D, Zhang H, Feng C, Wachsmann-Hogiu S, Walton JH, Cherry SR, Rowland DJ, Kukis D, Pan C, Lam KS, Nat. Commun 2014, 5, 4712. - PMC - PubMed

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