On the cytotoxicity of a cationic tertiary amine PEGylated nanogel as nanocarrier for anticancer therapies
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Research Letter
On the cytotoxicity of a cationic tertiary amine PEGylated nanogel as nanocarrier for anticancer therapies Lizbeth A. Manzanares-Guevara, and Angel Licea-Claverie, Centro de Graduados e Investigación en Química, Instituto Tecnológico de Tijuana, Tijuana, Baja California, C.P. 22000, México Irasema Oroz-Parra, Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada, Baja California, México; Facultad de Ciencias Marinas, Universidad Autónoma de Baja California, Ensenada, Baja California, C.P. 22860, México Alexei F. Licea-Navarro, Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Ensenada, Baja California, México Address all correspondence to Prof. Dr. Angel Licea-Claverie at [email protected] (Received 31 January 2018; accepted 22 May 2018)
Abstract Cationic PEGylated nanogels based on poly(N,N-diethylaminoethyl methacrylate) (PDEAEM) were prepared varying the ratio of PDEAEM to polyethyleneglycol (PEG), the initiator, and the crosslinker; resulting in nanogels of different surface charge (zeta-potential) and hydrodynamic diameter. Nanogels without PEG (100% PDEAEM) and nanogels containing 45 wt.% of PDEAEM were cytotoxic to human colon cancer cell line (HCT-116). Nanogels containing 20 wt.% or less of PDEAEM provided with a PEG shell were non-cytotoxic even at a concentration of 1 mg/mL. These nanogels loaded with 5-fluorouracil turned to be cytotoxic provoking cell death by apoptosis. Nanogels were also studied loaded with gold nanoparticles.
Introduction In recent years, new smart drug delivery systems have been developed to improve cancer therapy. The “leitmotif” is to achieve more effective treatment and fewer side effects.[1–3] Chemotherapy and radiotherapy, the most common conventional treatments, have some side effects, such as killing normal cells and neighbor tissues. The goal of a smart drug delivery system is to diminish these side effects by targeting cancer cells specifically. Research on smart drug delivery systems aims to exploit one or more of the following characteristics that differ in the tumor microenvironment and in the normal tissues: (1) the difference between extra-cellular pH values in tumors between 6.4–7.0 and 7.4 in healthy tissues; (2) the difference between intra- and extra-cellular pH with values for cancer cells between 4.5 and 6.0 in endosomolytic compartments and 6.8 and 7.0 on the outside; (3) the temperature difference between cancer cells and their surrounding area due to increased metabolism; (4) the vulnerability of cancer cells at 42–43 °C in contrast to 45–46 °C for normal cells; and finally (5) the higher enzyme concentration creating reductive/oxidizing (redox) conditions. In the past, by taking advantage of these factors: a series of smart nanocarriers were engineered for specific targeting and drug release in a controlled manner.[4–9] The architecture of the nanocarriers embraces: liposomes, micelles, nanotubes, nano
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