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  • br Minami D Takigawa N Takeda H Takata

    2020-08-30


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    Contents lists available at ScienceDirect
    Colloids and Surfaces B: Biointerfaces
    journal homepage: www.elsevier.com/locate/colsurfb
    Cationic versus anionic core-shell nanogels for transport of cisplatin to lung T cancer cells
    Alejandra Gonzalez-Uriasa, Ivan Zapata-Gonzalezb, , Angel Licea-Claveriea, , Alexei F. Licea-Navarroc, Johanna Bernaldez-Sarabiac, Karla Cervantes-Luevanoc
    a Tecnológico Nacional de México/I.T. de Tijuana, Centro de Graduados e Investigación en Química, A.P. 1166, C.P. 22000 Tijuana, B.C., Mexico
    b Cátedras CONACYT-Tecnológico Nacional de México/I.T. de Tijuana, Centro de Graduados e Investigación en Química, A.P. 1166, C.P. 22000, Tijuana, B.C., Mexico
    c Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Departamento de Innovación Biomédica, C.P. 22860, Ensenada, B.C., Mexico
    Keywords:
    Core-shell nanoparticles
    Nanogels
    Cisplatin
    Drug delivery
    pH-sensitive polymers
    Lung cancer 
    Stimuli-responsive polymeric nanogels have been proposed as nanocarriers of cisplatin to maximize its effect for cancer treatment. In this work, a comparative study between anionic core nanogels (ACN) and cationic core nanogels (CCN), both with PEGylated shells, has been performed. The nanogels were synthesized with different cross-linked cores: CCN with poly(N,N-diethylaminoethyl methacrylate) (PDEAEMA) and ACN with poly(2-methacryloyloxi benzoic acid) (P2MBA). Cisplatin chelate formation with carboxylic acids (ACN) or metal co-ordination with the amine groups (CCN) leads to a high loading of cisplatin into the nanocarriers. The nano-carriers ability to contain and modulate the supply of cisplatin was tested according to the pH of the medium, in which ACN efficiently released the drug at a typical pH value of a tumor tissue (pH = 6.8) while CCN only releases the drug at more acidic, endosome like, conditions (pH = 5). The effect of drug-free nanogels on cell lines NCI-H1437 (non-small cell lung carcinoma) was evaluated, showing biocompatibility at all concentrations studied (30–400 μg/mL) for both ACN and CCN. However, the survival percentage of the cells in contact with cisplatin-loaded nanogels were dependent on the dose, the time of contact and the type of nanogel. Cisplatin loaded CCN induced lower cell viability after 48 h of contact. Fluorescence microscopy showed a viable inter-nalization of the CCN nanogels, this was confirmed by flow cytometry in which 37.8% of cells contained drug loaded CCNs after 30 min of contact, representing a more effective nanocarrier for cisplatin to this cell-line.