Ovarian Cancer (OC) is one of the most lethal female malignancies worldwide, primarily due to its late-stage diagnosis and high recurrence rate. Nanotherapy in OC may provide significant and unique benefits for drug efficacy as well as for reducing the therapeutically limiting adverse effects associated with current treatment regimens. Herein, we report a nanoparticle (NP) formulation of poly(lactic-co-glycolic acid) (PLGA) stabilized with short peptides. PLGA is biodegradable and FDA-approved and amino acids of the peptide have Generally Regarded as Safe (GRAS) status.<br/><br/>The NP presented in this study is coated with a short hexapeptide of glutamic acid-lysine-histidine-phenylalanine x3 (EKHFFF). The EKHFFF peptide is designed to modulate the NP’s surface charge in different pH based on its isoelectric point (pI). This phenomenon can be used to target cancer cells, as circulatory-delivered NPs are expected to be negatively charged at physiological pH but switch to more positive charge values in the tumor’s lower pH microenvironment. This charge switch can potentially increase NP-cell interactions and contribute to higher cancer cell uptake. The NPs surface charge, as determined by Zeta Potential (ZP) measurements, is more negative in basic pH and more positive in acidic pH, as expected. The ZP range for the NPs is between -61 mV / pH 12 and -11 mV / pH 3. These surface charge changes are in agreement with the pI of the EKHFFF peptide, which is 6.85. Moreover, the NPs are spherical in morphology, as confirmed by transmission electron microscopy (TEM), with a diameter of 70 nm. This size is suitable for in vivo applications, as small-sized NPs can reach tumors through enhanced permeability and retention (EPR) effect. The tested NPs are stable in PBS and in serum for at least 72 hours. Finally, we present high resolution live cell imaging studies of the NPs uptake by OC cells, as well their distribution within cellular organelles.<br/><br/>In summary, the preliminary results demonstrate that pH-responsive peptide-coated NP platform can potentially be applied in OC therapy, which will be further explored in future studies.

Development of pH-responsive peptide-coated nanoparticles for targeting and drug delivery to ovarian cancer cells

ACS Spring 2022

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