Macromolecular Research, Vol.23, No.5, 474-484, May, 2015
Hybrid photoactive nanomaterial composed of gold nanoparticles, pheophorbide-A and hyaluronic acid as a targeted bimodal phototherapy
E-mail:,
Modern cancer research is largely focused on the design and development of multifunctional nanomaterials for cancer therapy and diagnosis. In this study, we fabricated a theranostic nanomaterial known as a photomedicine that combines a photothermal therapy (PTT), gold nanoparticles (AuNPs), a photodynamic therapy (PDT), pheophorbide-A (PheoA), and a cancer-targeting agent, hyaluronic acid (HA); this photomedicine also acts as a bimodal phototherapy. The combination of AuNPs and PheoA exerts a synergistic effect on PTT and PDT when irradiated by a laser source with a specific excitation wavelength. When excited by an external laser source, the hybrid nanomedicine generates singlet oxygen from PheoA while simultaneously generating heat from the AuNP, thus demonstrating a higher efficacy than any of the individual agents. The presence of HA on the outer surface of the Au accelerates the cellular uptake of the nanomedicine through CD44 receptors and prevents nonspecific accumulation of the drug in non-cancerous cells. The multifunctional nanoparticles have a diameter of ∼70 nm and show constant stability in different conditions for up to a week of observation. In vitro and in vivo studies have demonstrated that multifunctional nanomaterials selectively target cells overexpressing CD44 receptor. In vitro photo-activity assays in the lung cancer cell line (A549) show that over 95% of the cells were dead upon laser irradiation. In brief, this newly developed nanomaterial rapidly accumulates in the tumor within 3 h of IV administration and inhibits tumor growth by 95% upon laser irradiation compared with a saline-treated tumor model observed for 24 days.
- Celli JP, Spring BQ, Rizvi I, Evans CL, Samkoe KS, Verma S, Pogue BW, Hasan T, Chem. Rev., 110(5), 2795 (2010)
- Lovell JF, Liu TWB, Chen J, Zheng G, Chem. Rev., 110(5), 2839 (2010)
- Hamblin MR, Mroz P, Advances in Photodynamic Therapy, Artec House, Boston, 2008.
- Macdonald IJ, Dougherty TJ, J. Porphyr. Phthalocyanines, 5, 105 (2001)
- Huang P, Lin J, Wang XS, Wang Z, Zhang CL, He M, Wang K, Chen F, Li ZM, Shen GX, Cui DX, Chen XY, Adv. Mater., 24(37), 5104 (2012)
- Jang B, Choi Y, Theranostics, 2, 190 (2012)
- Lovell JF, Jin CS, Huynh E, Jin HL, Kim C, Rubinstein JL, Chan WCW, Cao WG, Wang LV, Zheng G, Nat. Mater., 10(4), 324 (2011)
- Jang B, Park JY, Tung CH, Kim IH, Choi Y, ACS Nano, 5, 1086 (2011)
- Duncan B, Kim C, Rotello VM, J. Control. Release, 148, 122 (2010)
- Nguyen DT, Kim DJ, Kim KS, Micron, 42, 207 (2011)
- Hong R, Han G, Fernandez JM, Kim BJ, Forbes NS, Rotello VM, J. Am. Chem. Soc., 128(4), 1078 (2006)
- Wang J, Zhu G, You M, Song E, Shukoor MI, Zhang K, Altman MB, Chen Y, Zhu Z, Huang CZ, ACS Nano, 6, 5070 (2012)
- Gao L, Fei J, Zhao J, Li H, Cui Y, Li J, ACS Nano, 6, 8030 (2012)
- Cheng Y, Samia AC, Meyers JD, Panagopoulos I, Fei BW, Burda C, J. Am. Chem. Soc., 130(32), 10643 (2008)
- Lee H, Mok H, Lee S, Oh YK, Park TG, J. Control. Release, 119, 245 (2007)
- Park W, Kim KS, Bae BC, Kim YH, Na K, Eur. J. Pharm. Sci., 40, 367 (2010)
- He M, Zhao Z, Yin L, Tang C, Yin C, Int. J. Pharm., 373, 165 (2009)
- Yu MK, Park J, Jon S, Theranostics, 2, 3 (2012)
- Platt VM, Szoka FC Jr., Mol. Pharm., 5, 474 (2008)
- Ibrahim EM, Stewart RL, Corke K, Blackett AD, Tidy JA, Wells M, Int. J. Gynecol. Cancer., 16, 1631 (2006)
- Smith SM, Cai L, PLoS One, 7, e50867 (2012).
- Tabrizil TA, Ayhan F, Ayhan H, Hacettepe, J. Biol. Chem., 37, 217 (2009)
- Li L, Nurunnabi M, Nafiujjaman M, Lee YK, Huh KM, J. Control. Release, 171, 241 (2013)
- Li F, Bae BC, Na K, Bioconjugate Chem., 21, 1312 (2010)
- Lee MY, Yang JA, Jung HS, Beack SG, Choi JE, Hur WH, Koo HB, Kim K, Yoon SK, Hahn SK, ACS Nano, 6, 9522 (2012)
- Li L, Nurunnabi M, Nafiujjaman M, Jeong YY, Lee YK, Huh KM, J. Mater. Chem. B, 2, 2929 (2014)
- Nurunnabi M, Khatun Z, Nafiujjaman M, Lee DG, Lee YK, ACS Appl. Mater. Interfaces, 5, 8246 (2013)
- Lin J, Wang S, Huang P, Wang Z, Chen S, Niu G, Li W, He J, Cui D, Lu G, Chen X, Nie Z, ACS Nano, 7, 5320 (2013)
- Li L, Bae B, Tran TH, Yoon KH, Na K, Huh KM, Carbohydr. Polym., 86, 708 (2011)
- Zhou J, Lu Z, Zhu X, Wang X, Liao Y, Ma Z, Li F, Biomaterials, 34, 9584 (2013)
- Nurunnabi M, Khatun Z, Huh KM, Park SY, Lee DY, Cho KJ, Lee YK, ACS Nano, 7, 6858 (2013)
- Nurunnabi M, Cho KJ, Choi JS, Huh KM, Lee YK, Biomaterials, 31, 5436 (2010)
- Nurunnabi M, Khatun Z, Reeck GR, Lee DY, Lee YK, Chem. Commun., 49, 5079 (2013)
- Chan JY, Tang PM, Hon PM, Au SW, Tsui SK, Waye MM, Kong SK, Mak TC, Fung KP, Planta Med., 72, 28 (2006)
- Lee H, Lee K, Park TG, Bioconjugate Chem., 19, 1319 (2008)
- Vijayakumar S, Int. J. Curr. Sci., 11, E84 (2014)
- Lin J, Wang S, Huang P, Wang Z, Chen S, Niu G, Li W, He J, Cui D, Lu G, Chen X, Nie Z, ACS Nano, 7, 5320 (2013)