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Merck

Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells.

International journal of molecular sciences (2020-05-30)
Anine Crous, Heidi Abrahamse
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Cancer stem cells (CSCs) are a leading contributor to lung cancer mortality rates. CSCs are responsible for tumor growth and recurrence through inhibition of drug-induced cell death, decreasing the effect of traditional cancer therapy and photodynamic therapy (PDT). PDT can be improved to successfully treat lung cancer by using gold nanoparticles (AuNPs), due to their size and shape, which have been shown to facilitate drug delivery and retention, along with the targeted antibody (Ab) mediated selection of CSCs. In this study, a nanobioconjugate (NBC) was constructed, using a photosensitizer (PS) (AlPcS4Cl), AuNPs and Abs. The NBC was characterized, using spectroscopy techniques. Photodynamic effects of the NBC on lung CSCs was evaluated, using biochemical assays 24 h post-irradiation, in order to establish its anticancer effect. Results showed successful conjugation of the nanocomposite. Localization of the NBC was seen to be in integral organelles involved in cell homeostasis. Biochemical responses of lung CSCs treated using AlPcS4Cl -AuNP and AlPcS4Cl-AuNP-Ab showed significant cell toxicity and cell death, compared to free AlPcS4Cl. The PDT effects were enhanced when using the NBC, showing significant lung CSC destruction to the point of eradication.

MATERIALS
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Sigma-Aldrich
N-Hydroxysulfosuccinimide sodium salt, โ‰ฅ98% (HPLC)
Sigma-Aldrich
Penicillin-Streptomycin, Solution stabilized, with 10,000 units penicillin and 10 mg streptomycin/mL, 0.1 μm filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, ≥96% (agarose gel electrophoresis)
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RPMI-1640 Medium, With L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
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Amphotericin B solution, 250 μg/mL in deionized water, 0.1 μm filtered, BioReagent, suitable for cell culture
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MES, low moisture content, ≥99% (titration)
Sigma-Aldrich
Phosphate buffered saline, powder, pH 7.4, for preparing 1 L solutions