Article

Layer-by-layer assembly of graphene oxide on thermosensitive liposomes for photo-chemotherapy

Mohadeseh HashemiDepartment of Biomedical Engineering, Faculty of New Sciences and Technologies, The University of Tehran, Tehran, Iran; Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA; Division of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, USAMeisam OmidiProtein Research Center, Shahid Beheshti University, GC, Velenjak, Tehran, IranBharadwaj MuralidharanDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, USA; Department of Electrical and Computer Engineering, The University of Texas at Austin, Austin, USALobat TayebiDepartment of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, USAMatthew J. HerpinDivision of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, USAMohammad Ali MohagheghiCancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, IranJavad MohammadiDepartment of Biomedical Engineering, Faculty of New Sciences and Technologies, The University of Tehran, Tehran, Iran. Electronic address: [email protected]Hugh D. C. SmythDivision of Pharmaceutics, College of Pharmacy, The University of Texas at Austin, Austin, USA. Electronic address: [email protected]Thomas E. MilnerDepartment of Biomedical Engineering, The University of Texas at Austin, Austin, USA. Electronic address: [email protected]

2017en

ABI

Abstract

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 liposomes encapsulating 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 potential of +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.

Identifiers

DOI: 10.1016/j.actbio.2017.10.040

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