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Targeted drug delivery system for ribonuclease A
Author(s) -
BarcelóBovea Vanessa Celeste,
Griebenow Kai,
CruzMontañez Alejandra
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.823.2
Subject(s) - plga , ethylene glycol , hela , in vivo , chemistry , folate receptor , drug delivery , ribonuclease , dynamic light scattering , peg ratio , nanoparticle , biophysics , cancer cell , in vitro , biochemistry , materials science , nanotechnology , cancer , organic chemistry , rna , gene , economics , biology , medicine , microbiology and biotechnology , finance
Ribonuclease A is a very accessible protein that has been tested as a therapeutic for cancer in vitro and in vivo due to its ability to hinder protein production and induce cell death. However, the results in vivo were only positive when high amounts of enzyme were injected directly in the tumors. To overcome this limitation we are testing the use of a drug delivery system consisting of nanoparticles made out of the protein itself coated with poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐folate conjugates (PLGA‐PEG‐FA), in which the folate moiety confers selectivity towards cells overexpressing folic acid receptors on their membrane. Using a solvent displacement nanoprecipitation method we obtained nanoparticles constituted of ribonuclease A. Nanoparticles obtained under different conditions were analyzed by scanning electron microscope and dynamic light scattering, confirming spherical shape and an average size of 600 nm. The FA‐PEG‐PLGA copolymer to coat the nanoparticles was synthesized by conjugating the free alcohol group in PLGA with the carboxyl group in the folate‐conjugated‐PEG. The structure of the product was confirmed by 1 H‐NMR. Experiments for coating optimization are in process and the efficacy of the system will be tested in HeLa cells as well as normal cells to confirm the selectivity. This drug delivery system does not have the limitation of a maximum loading capacity, and has been proven by us to efficiently deliver other proteins to cancer cells. Therefore, it is expected to selectively deliver higher amounts of ribonuclease A to cancer cells than previously reported systems. Support or Funding Information Supported by the MSRC (Molecular Science Research Center)