Redox/photo dual-responsive, self-targeted, and photosensitizer-laden bismuth sulfide nanourchins for combination therapy in cancer
- 15 December 2020
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Nanoscale
- Vol. 13 (2), 1231-1247
- https://doi.org/10.1039/d0nr07736d
Abstract
Targeted and stimuli-sensitive nanobombs for the release of therapeutic agents after laser irradiation of the tumor site are gaining widespread attention as personalized anticancer regimens. In this study, redox and photo dual-responsive, folate receptor-targeted nanourchin carriers for chemo-, photodynamic, and photothermal therapy were constructed by the amalgamation of an outer layer of polyethylene glycol (PEG)-S-S-methotrexate (MTX) and an inner core of indocyanine green (ICG)-loaded bismuth sulfide (Bi2S3) nanoparticles for cancer treatment. MTX introduces the carrier to folate receptors resulting in the internalization of nanoparticles into cancer cells, specifically and increasingly. In the reducing environment inside cancer cells, MTX was cleaved, resulting in a burst release that effectively inhibited tumor growth. Simultaneously, the fusion of Bi2S3 and ICG in the inner core absorbed energy from a near-infrared radiation (NIR) laser to generate heat and reactive oxygen species, which further ablated the tumors and synergistically enhanced the anticancer activity of MTX. These results indicate the successful preparation of combined nanourchins (NUs) showing GSH-induced and laser-responsive release of MTX and ICG, accompanied by hyperthermia via Bi2S3 and ICG. Effective in vitro cellular internalization, cellular cytotoxicity, and pro-apoptotic behavior of the nanosystem were achieved through a targeting, redox, and NIR-responsive combination strategy. In vivo biodistribution and photothermal imaging also revealed tumor-selective and -retentive, as well as thermally responsive attributes. Ultimately, this in vivo antitumor study shows an effective tumor ablation by these nanourchins without affecting the vital organs. Our findings indicate that this targeted redox- and laser-responsive combination therapeutic carriers can be a promising strategy in folate receptor-expressing tumors.Keywords
Funding Information
- Ministry of Science, ICT and Future Planning (2018R1A2A2A05021143, 2015R1A5A2009124)
This publication has 57 references indexed in Scilit:
- Covalent conjugation of graphene oxide with methotrexate and its antitumor activityChemical Physics Letters, 2013
- Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in ratBMC Gastroenterology, 2012
- Engineered Redox‐Responsive PEG Detachment Mechanism in PEGylated Nano‐Graphene Oxide for Intracellular Drug DeliverySmall, 2012
- X‐Ray Computed Tomography Imaging of Breast Cancer by using Targeted Peptide‐Labeled Bismuth Sulfide NanoparticlesAngewandte Chemie, 2011
- Large‐Scale Synthesis of Bi2S3 Nanodots as a Contrast Agent for In Vivo X‐ray Computed Tomography ImagingAdvanced Materials, 2011
- Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene deliveryJournal of Controlled Release, 2011
- Hetero-Epitaxial Anion Exchange Yields Single-Crystalline Hollow NanoparticlesJournal of the American Chemical Society, 2009
- Delivery of Nucleic Acids via Disulfide‐Based Carrier SystemsAdvanced Materials, 2009
- Cytotoxic drug-induced, p53-mediated upregulation of caspase-8 in tumor cellsOncogene, 2007
- Formation of Hollow Nanocrystals Through the Nanoscale Kirkendall EffectScience, 2004