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Targeted Delivery of Cytochrome c‐based Nanoparticles Coated with a Poly(lactic‐co‐glycolic acid) ‐Poly(ethylene glycol)‐Folate Conjugate to HeLa Cells
Author(s) -
MoralesCruz Moraima,
Cruz Alejandra,
GonzálezRobles Tania,
Figueroa Cindy,
Muñoz Laura,
Molina Anna,
Griebenow Kai
Publication year - 2015
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.29.1_supplement.897.10
Subject(s) - hela , cytochrome c , plga , chemistry , apoptosis , cancer cell , ethylene glycol , glycolic acid , endosome , biophysics , cell culture , cytotoxicity , cytoplasm , cell , biochemistry , in vitro , biology , lactic acid , cancer , genetics , organic chemistry , bacteria
The inactivation of the upstream components of the signaling pathways (such as the p53 pathway) that activate the release of Cytochrome c (Cyt c) from the mitochondria to the cytoplasm in response to DNA damage avoid the apoptosis mechanism in many cancer cells. To overcome this, we aim at delivering Cyt c to the cytoplasm of cancer cells. Indeed, recently, we demonstrated that Cyt c nanoparticles were able to induce programmed cell death in an in vitro cell culture study. These nanoparticles consisted of a Cyt c core stabilized by a cover consisting of PLGA, a FDA approved polymer. Herein we extend this study by transforming the system into an active delivery system. The ligand chosen, FA, was linked to poly(ethylene glycol) (FA‐PEG) and that to PLGA in order to target folate over‐expressing cells. The construct should also avoid RES uptake and facilitate cellular uptake. In comparison to the initial system, the improved one shows enhanced stimulus release properties and higher cell cytotoxicity under the same conditions. The FA‐PEG‐PLGA‐Cyt c NPs was able to reduce the cell viability to 20% whereas the same complex without FA (i.e. PEG‐PLGA‐Cyt c NPs) only reduced it to 80% in HeLa cells which is a folate positive cell line. In addition, confocal microscopy shows that the FA‐PEG‐PLGA‐Cyt c NPs was internalized by HeLa cells and that the bioconjugate was capable of endosomal escape. The results clearly demonstrate that the new complex is able to improve the Cyt c stabilization upon formulation of a smart drug delivery system and to increase the tumor specificity of the Cyt c‐based NPs.