Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide†

doi:10.7503/cjcu20180181

Abstract

Abstract:

Partially reduced grphene oxide(pRGO) is synthesized using a mild reduction method by incubating GO suspension under alkaline condition at room tempeature. Aptamer(AS1411) non-covalent binding with cardiogreen(ICG), a photosensitizer and photothermal effect molecule, to the surface of pRGO, was used to target cancer cells for photodynamic therapy(PDT) and photothermal therapy(PTT). Structure and morphology of the as-synthesized pRGO and pRGO-AS1411-ICG(pRAI) nanocomposites were confirmed by menas of FTIR, Raman, XPS, UV-Vis, transmission electron microscopy(TEM) and energy dispersive spectrometer(EDS). pRAI targets cancer cells with AS1411 to produce singlet oxygen for PDT and photothermal effect for PTT upon near-infrared(NIR) light irradiation. Since pRGO is decorated with several AS1411-ICG molecules, the pRGO-AS1411-ICG conjugate yields enhanced binding and therapeutic effect by the added ability to carry multiple photosensitizers. Consequently, pRAI offers a remarkably improved and synergistic therapeutic effect on cells.

Key words: Partially reduced graphene oxide, Nanocomposite, Photothermal therapy, Photodynamic therapy, Tumor cell

CLC Number:

TrendMD:

WANG Xueli,WANG Zhenxin. Preparation of a Targeted Tumor Nanocomposites for Combined Photodynamic-photothermal Therapy Based on Partially Reduced Graphene Oxide^†[J]. Chem. J. Chinese Universities, 2018, 39(10): 2185.

Figures/Tables 7

Scheme 1 Schematic illustration of the synthesis of pRAI

Scheme 2 Schematic presentation of pRAI targeted to HeLa for combined photothermal and photodynamic therapy

Fig.1 UV-Vis absorption spectra of GO(0.02 mg/mL) and pRGO(0.02 mg/mL)(A), TEM images of GO(B1) and pRGO(B2), the curves of pRGO(0.02 mg/mL) in water for 0—14 d(C) and UV-Vis absorption spectra of pRGO(0.02 mg/mL) and pRAI(0.02 mg/mL pRGO)(D)Inset of (A) shows 500—900 nm spectrum and the suspensions of GO(1 mg/mL ) and pRGO(1 mg/mL ); inset of (D) shows UV-Vis absorption spectrum of ICG(40 μmol/L).

Table 1 EDS results of GO and pRGO

Element	Mass(%)		Atomic(%)
Element	GO	pRGO	GO	pRGO
C	61.27	64.09	67.82	71.40
O	38.73	31.95	32.18	26.72
P	—	0.22	—	0.10
S	—	1.60	—	0.67

Fig.2 C1s XPS spectra of GO(A), pRGO(B), full XPS spectra of pRGO and pRAI(C), ATR-FTIR spectra of GO, pRGO and pRAI(D), Raman spectra of GO, pRGO and pRAI(E) and photothermal heating curves of ICG(40 μmol/L), pRGO(200 μg/mL) and pRAI(200 μg/mL), as a function of the irradiation time under continuous laser irradiation at a power intensity of 1.65 W/cm2(F)

Fig.3 Cytotoxicity evaluation test of HeLa cells with different concentrations of pRGO, AS1411, ICG and pRAI(A), calcein AM/PI staining to visualize Hela cell viability treated by pRGO, AS1411, ICG and pRAI(B), cell viability studies with pRGO, AS1411, ICG and pRGO with laser irradiation(808 nm, 1.65 W/cm2 for 10 min)(C) and fluorescence microscope images of cell treated pRGO, AS1411, ICG and pRAI with laser irradiation(808 nm, 1.65 W/cm2 for 10 min)(D)

Fig.4 Cell viability studies with different concentrations of pRAI with and wihout laser irradiation(808 nm,1.65 W/cm2 for 10 min)(A) and fluorescence microscope cell images of SOSG with laser irradiation(808 nm,1.65 W/cm2 for 10 min)(B)

References 24

[1]	Lucky S.S., Soo K. C., Zhang Y., Chem. Rev., 2015, 115, 1990—2042
[2]	Cai Y., Liang P.P., Tang Q. Y., Yang X. Y., Si W. L., Huang W., Zhang Q., Dong X. C., ACS Nano, 2017, 11, 1054—1063
[3]	Yang K., Wan J., Zhang S., Tian B., Zhang Y., Liu Z., Biomaterials, 2012, 33, 2206—2214
[4]	Wang Y.H., Deng H. H., Liu Y. H., Shi X. Q., Liu A. L., Peng H. P., Hong G. L., Chen W., Biosensors and Bioelectronics, 2016, 80, 140—145
[5]	Akiyama Y., Mori T., Katayama Y., Niidome T., J. Control Release, 2009, 139, 81—84
[6]	Chen R., Wang X, Yao X.K., Zheng X. C., Wang J., Jiang X. Q., Biomaterials, 2013, 34, 8314—8322
[7]	Shiao Y.S., Chiu H. H., Wu P. H., Huang Y. F., ACS Appl. Mater.Interfaces, 2014, 6, 21832—21841
[8]	González-Delgado José A., Kennedy P.J., Ferreira M., ToméJoao P. C., Sarmento B., J. Med. Chem., 2016, 59, 4428—4442
[9]	Barth B.M., Altinoglu E. I., Shanmugavelandy S. S., Kaiser J. M., Crespo-Gonzalez D., DiVittore N. A., McGovern C., Goff T. M., Keasey N. R., Adair J. H., Loughran T. P. Jr., Claxton D. F., Kester M., ACS Nano, 2011, 5, 5325—5337
[10]	Yoon H.K., Ray A., Lee Y. E., Kim G., Wang X., Kopelman R., J. Mater. Chem., 2013, 1, 5611—5619
[11]	De la Zerda A., Zavaleta C., Keren S., Vaithilingam S., Bodapati S., Liu Z., Levi J., Smith B. R., Ma T. J., Oralkan O., Cheng Z., Chen X., Dai H., Khuri-Yakub B. T., Gambhir S. S., Nat. Nanotechnol., 2008, 3, 557—562
[12]	Huang Y.F., Chang H. T., Tan W., Anal. Chem., 2008, 80, 567—572
[13]	Tang Z., Zhu Z., Mallikaratchy P., Yang R., Sefah K., Tan W., Chem. Asian J., 2010, 5, 783—786
[14]	Shieh Y.A., Yang S. J., Wei M. F., Shieh M. J., ACS Nano, 2010, 4, 1433—1442
[15]	Liu J.B., Li Y. L., Li Y. M., Li J. H., Deng Z. X., J. Mater. Chem., 2010, 20, 900—906
[16]	Lin Z.Y., Yao Y. G., Li Z., Liu Y., Li Z., Wong C. P., J. Phys. Chem.C, 2010, 114, 14819—14825
[17]	Zhang W., Zhang Y.X., Tian Y., Yang Z. Y., Xiao Q. Q., Guo X., Jing L., Zhao Y. F., Yan Y. M., Feng J. S., Sun K. N., ACS Appl. Mater.Interfaces, 2014, 6, 2248—2254
[18]	Stathi P., Gournis D., Deligiannakis Y., Rudolf P., Langmuir, 2015, 31, 10508—10516
[19]	Padilha M., Siqueira E Jesus M., Ceragiol H., Batista Â., Nyúl-Tóth Á Molnár J., Wilhelm I., Maróstica M.Jr., Krizbai I., Cruz-Höfling M., Mol.Pharmaceutics, 2016, 13, 3913—3924
[20]	Zhang Y.T., Liu S., Li Y., Deng D. M., Si X. J., Ding Y. P., He H. B., Luo L. Q., Wang Z. X., Biosensors and Bioelectronics, 2015, 66, 308—315
[21]	Ambros A., Chua C.K., Bonanni A., Pumera M., Chem. Mater., 2012, 24, 2292—2298
[22]	Lepock J.R., Int. J. Hyperthermia, 2003, 19, 252—266
[23]	Xu Y.X., Bai H., Lu G. W., Li C., Shi G. Q., J. Am. Chem. Soc., 2008, 130, 5856—5857
[24]	Xu Y.X., Zhao L., Bai H., Hong W. J., Li C., Shi G. Q., J. Am. Chem. Soc., 2009, 131, 13490—13497