Verteporfin-Loaded Poly(ethylene glycol)-Poly(beta-amino ester)-Poly(ethylene glycol) Triblock Micelles for Cancer Therapy
Year: 2018
Type: article
Abstract: Amphiphilic polymers can be used to form micelles to deliver water-insoluble drugs. A biodegradable poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)-PEG triblock copolymer was developed that is useful for drug delivery. It was shown to successfully encapsulate and pH-dependently release a water-insoluble, small molecule anticancer drug, verteporfin. PEG-PBAE-PEG micelle morphology was also controlled through variations to the hydrophobicity of the central PBAE block of the copolymer in order to evade macrophage uptake. Spherical micelles were 50 nm in diameter, while filamentous micelles were 31 nm in width with an average aspect ratio of 20. When delivered to RAW 264.7 mouse macrophages, filamentous micelles exhibited a 89% drop in cellular uptake percentage and a 5.6-fold drop in normalized geometric mean cellular uptake compared to spherical micelles. This demonstrates the potential of high-aspect-ratio, anisotropically shaped PEG-PBAE-PEG micelles to evade macrophage-mediated clearance. Both spherical and filamentous micelles also showed therapeutic efficacy in human triple-negative breast cancer and small cell lung cancer cells without requiring photodynamic therapy to achieve an anticancer effect. Both spherical and filamentous micelles were more effective in killing lung cancer cells than breast cancer cells at equivalent verteporfin concentrations, while spherical micelles were shown to be more effective than filamentous micelles against both cancer cells. Spherical and filamentous micelles at 5 and 10 μM respective verteporfin concentration resulted in 100% cell killing of lung cancer cells, but both micelles required a higher verteporfin concentration of 20 μM to kill breast cancer cells at the levels of 80% and 50% respectively. This work demonstrates the potential of PEG-PBAE-PEG as a biodegradable, anisotropic drug delivery system as well as the in vitro use of verteporfin-loaded micelles for cancer therapy.
Source: Biomacromolecules
Authors: Jayoung Kim, James G. Shamul, Sagar R. Shah, Alyssa Shin, Ben J. Lee, Alfredo Quinones-Hinojosa, Jordan J. Green
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
Funders: Mayo Clinic, United States Pharmacopeia, Mayo Foundation for Medical Education and Research, National Institutes of Health, Samsung, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, State of Florida
Awards: G1691785618, G1770458650, G2687943803, G2895917680, G3273814005, Nanoparticle Modified Human Fat Derived Mesenchymal Stem Cells for Brain Cancer (Change of Organization Application), BMP4 Engineered Mesenchymal Stem Cell Therapy for Glioblastoma, G4400497369, G4447472125, A novel microfluidic device to predict brain cancer prognosis and response to therapy, G5932050230, Gene Delivery Nanoparticles to Treat Glioblastoma, G8332239442, G922751558
OpenAlex ID: W2810967230