Carla Arnau del Valle, Payal Srivastava, Kathryn McNaughton, Huang‐Chiao Huang
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Self‐assembly of verteporfin dimers into folate receptor‐targeted lipid nanoparticles for photodynamic therapy of ovarian cancer
Photodynamic therapy (PDT) is a minimally invasive treatment that involves the administration of a light‐activatable drug followed by light activation of the lesion to produce reactive oxygen species that kill cancer cells. Visudyne®, a liposomal formulation of benzoporphyrin derivative (BPD) photosensitizer, is clinically approved for PDT of ocular diseases and is now being tested for PDT and imaging of pancreatic, brain, and other cancers. While Visudyne® improves the pharmacokinetics of BPD, it lacks treatment selectivity. To reduce PDT‐associated side effects such as skin and bowel toxicity while enhancing therapeutic outcomes, developing cancer‐targeted BPD nanotechnology is essential. Many cancers are characterized by overexpression of folate receptor (FR) and present high levels of glutathione (GSH). Here, we report the synthesis of a dimeric‐BPD (dBPD) activatable by red light for PDT and imaging of cancer cells. Self‐assembled lipid nanoparticles (NPs) are developed by the aggregation of dBPD and further functionalized with FA (FA‐dBPD‐NPs) and with drug release capability via cleavage of the disulfide linkers through GSH. The FA‐dBPD‐NPs present high drug payload, GSH‐triggered release effect, FRs overexpressing cell targeting, endoplasmic reticulum accumulation, and effective PDT in ovarian cancer cells.
期刊介绍:
Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.