International Journal of Nanomedicine (Jan 2023)

Multifunctional Nanoparticles Codelivering Doxorubicin and Amorphous Calcium Carbonate Preloaded with Indocyanine Green for Enhanced Chemo-Photothermal Cancer Therapy

  • Yu J,
  • Wang L,
  • Xie X,
  • Zhu W,
  • Lei Z,
  • Lv L,
  • Yu H,
  • Xu J,
  • Ren J

Journal volume & issue
Vol. Volume 18
pp. 323 – 337

Abstract

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Jingmou Yu,1– 3 Liangliang Wang,4 Xin Xie,2 Wenjing Zhu,3 Zhineng Lei,3 Linghui Lv,3 Hongling Yu,3 Jing Xu,4 Jin Ren2,3 1Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, People’s Republic of China; 2Jiangxi Provincial Laboratory Laboratory of System Biomedicine, Jiujiang University, Jiujiang, People’s Republic of China; 3School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, People’s Republic of China; 4Affiliated Hospital of Jiujiang University, Jiujiang, People’s Republic of ChinaCorrespondence: Jingmou Yu; Jin Ren, Email [email protected]; [email protected]: Multifunctional stimuli-responsive nanoparticles with photothermal-chemotherapy provided a powerful tool for improving the accuracy and efficiency in the treatment of malignant tumors.Methods: Herein, photosensitizer indocyanine green (ICG)-loaded amorphous calcium-carbonate (ICG@) nanoparticle was prepared by a gas diffusion reaction. Doxorubicin (DOX) and ICG@ were simultaneously encapsulated into poly(lactic-co-glycolic acid)-ss-chondroitin sulfate A (PSC) nanoparticles by a film hydration method. The obtained PSC/ICG@+DOX hybrid nanoparticles were characterized and evaluated by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC). The cellular uptake and cytotoxicity of PSC/ICG@+DOX nanoparticles were analyzed by confocal laser scanning microscopy (CLSM) and MTT assay in 4T1 cells. In vivo antitumor activity of the nanoparticles was evaluated in 4T1-bearing Balb/c mice.Results: PSC/ICG@+DOX nanoparticles were nearly spherical in shape by TEM observation, and the diameter was 407 nm determined by DLS. Owing to calcium carbonate and disulfide bond linked copolymer, PSC/ICG@+DOX nanoparticles exhibited pH and reduction-sensitive drug release. Further, PSC/ICG@+DOX nanoparticles showed an effective photothermal effect under near-infrared (NIR) laser irradiation, and improved cellular uptake and cytotoxicity in breast cancer 4T1 cells. Importantly, PSC/ICG@+DOX nanoparticles demonstrated the most effective suppression of tumor growth in orthotopic 4T1-bearing mice among the treatment groups. In contrast with single chemotherapy or photothermal therapy, chemo-photothermal treatment by PSC/ICG@+DOX nanoparticles synergistically inhibited the growth of 4T1 cells.Conclusion: This study demonstrated that PSC/ICG@+DOX nanoparticles with active targeting and stimuli-sensitivity would be a promising strategy to enhance chemo-photothermal cancer therapy.Graphical Abstract: Keywords: chemo-photothermal treatment, amorphous calcium carbonate, nanoparticles, stimuli-sensitivity, drug delivery, cancer therapy

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