Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited on cationic liposomesencapsulating doxorubicin. Various concentrations of GO and GO-PLL were examined and the optimal LBL Lipo-graph was found to have a particle size of 267.9 ± 13 nm, zeta potentialof +43.9 ± 6.9 mV and encapsulation efficiency of 86.4 ± 4.7%. The morphology of LBL Lipo-graph was examined by cryogenic-transmission electron microscopy (Cryo-TEM), atomic force microcopy (AFM) and scanning electron microscopy (SEM). The buildup of LBL Lipo-graph was confirmed via ultraviolet-visible (UV–Vis) spectrophotometry, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis. Infra-red (IR) response suggests that four layers are sufficient to induce a gel-to-liquid phase transition in response to near infra-red (NIR) laser irradiation. Light-matter interaction of LBL Lipo-graph was studied by calculating the absorption cross section in the frequency domain by utilizing Fourier analysis. Drug release assay indicates that the LBL Lipo-graph releases much faster in an acidic environment than a liposome control. A cytotoxicity assay was conducted to prove the efficacy of LBL Lipo-graph to destroy MD-MB-231 cells in response to NIR laser emission. Also, image stream flow cytometry and two photon microcopy provide supportive data for the potential application of LBL Lipo-graph for photothermal therapy. Study results suggest the novel dual-sensitive nanoparticles allow intracellular doxorubin delivery and respond to either acidic environments or NIR excitation.
Statement of Significance
Stimuli sensitive hybrid nanoparticles have been synthesized using a layer-by-layer technique and demonstrated for dual chemo-photothermal destruction of breast cancer cells. The hybrid nanoparticles are composed of alternating layers of graphene oxide and graphene oxide conjugated poly-l-lysine coating the surface of a thermosensitive cationic liposome containing doxorubicin as a core. Data suggests that the hybrid nanoparticles may offer many advantages for chemo-photothermal therapy. Advantages include a decrease of the initial burst release which may result in the reduction in systemic toxicity, increase in pH responsivity around the tumor environment and improved NIR light absorption.
Hashemi, Mohadeseh; Omidi, Meisam; Muralidharan, Bharadwaj; Tayebi, Lobat; Herpin, Matthew J.; Mohagheghi, Mohammad Ali; Mohammadi, Javad; Smyth, Hugh D.C.; and Milner, Thomas E., "Layer-By-Layer Assembly of Graphene Oxide on Thermosensitive Liposomes for Photo-Chemotherapy" (2018). School of Dentistry Faculty Research and Publications. 289.