1. Glucose-Targeted Hydroxyapatite/Indocyanine Green Hybrid Nanoparticles for Collaborative Tumor Therapy.
- Author
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Cheng X, Xu Y, Zhang Y, Jia C, Wei B, Hu T, Tang R, and Li C
- Subjects
- Acrylic Resins chemistry, Acrylic Resins toxicity, Animals, Antineoplastic Agents chemistry, Antineoplastic Agents toxicity, Apoptosis drug effects, Calcium metabolism, Drug Carriers chemistry, Drug Carriers therapeutic use, Drug Carriers toxicity, Durapatite chemistry, Durapatite toxicity, Glucose chemistry, Glucose toxicity, Hep G2 Cells, Humans, Indocyanine Green chemistry, Indocyanine Green radiation effects, Indocyanine Green toxicity, Infrared Rays, Male, Mice, Inbred ICR, Nanoparticles chemistry, Nanoparticles radiation effects, Nanoparticles toxicity, Photochemotherapy, Photosensitizing Agents chemistry, Photosensitizing Agents radiation effects, Photosensitizing Agents toxicity, Photothermal Therapy, Mice, Antineoplastic Agents therapeutic use, Durapatite therapeutic use, Indocyanine Green therapeutic use, Nanoparticles therapeutic use, Neoplasms drug therapy, Photosensitizing Agents therapeutic use
- Abstract
Nanoscale hydroxyapatite (nHA) is considered as a promising drug carrier or therapeutic agent against malignant tumors. But the strong agglomeration tendency and lack of active groups seriously hamper their usage in vivo . To address these issues, we fabricated an organic-inorganic hybrid nanosystem composed of poly(acrylic acid) (PAA), nHA, and indocyanine green (ICG), and further modified with glucose to give a targeting nanosystem (GA@HAP/ICG-NPs). These hybrid nanoparticles (∼90 nm) showed excellent storage and physiological stability assisted by PAA and had a sustained drug release in an acidic tumor environment. In vitro cell experiments confirmed that glucose-attached particles significantly promoted cellular uptake and increased intracellular ICG and Ca
2+ concentrations by glucose transporter 1 (GLUT1)-mediated endocytosis. Subsequently, the excessive Ca2+ induced cell or organelle damage and ICG triggered photothermal and photodynamic effects (PTT/PDT) under laser irradiation, resulting in enhanced cell toxicity and apoptosis. In vivo tests revealed that the hybrid nanosystem possessed good hemocompatibility and biosafety, facilitating in vivo circulation and usage. NIR imaging further showed that tumor tissues had more drug accumulation, resulting in the highest tumor growth inhibition (87.89%). Overall, the glucose-targeted hybrid nanosystem was an effective platform for collaborative therapy and expected to be further used in clinical trials.- Published
- 2021
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