화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.102, 1-16, October, 2021
DOI10.1016/j.jiec.2021.06.004  Export Citation
In vitro intracellular studies of pH and thermo-triggered doxorubicin conjugated magnetic SBA-15 mesoporous nanocarriers for anticancer activity against hepatocellular carcinoma
Ndumiso Vukile Mdlovu, Kuen-Song Lin†, Meng-Tzu Weng1, †, Chi-Cheng Hsieh1, You-Sheng Lin, and Maria Janina Carrera Espinoza
  • Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung–Li District, Taoyuan City 32003, Taiwan
  • 1Department of Internal Medicine, National Taiwan University Hospital, Taipei 100233, Taiwan
E-mail:,
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, accounting for about 75% of all liver cancers. It is the third most common basis for cancer mortality worldwide, and unfortunately, its treatme nt is often limited by the shortage of appropriate therapeutic options and side effects causedby the current treatment methods. To overcome this, doxorubicin (DOX)-loaded pH-/thermoresponsive magnetic mesoporous nanocarriers were formulated and evaluated for their in vitro anticancer activity against HCC. These nanocarriers consist of iron oxide (IO) nanoparticles conjugated with SBA-15 (S15) and Pluronic F127 (PF) to form IOS15 nanocomposites and IOS15@PF nanocarriers. The prepared nanocarriers were superparamagnetic with saturation magnetizations of IOS15 and IOS15@PF being 76.3 and 72.1 emu/g, respectively. Small-angle neutron/X-ray scattering (SANS/SAXS) studies showed that the developed nanocarriers are temperature-sensitive and possess hexagonally arranged structures. Cell viability studies demonstrated that IOS15@PF@DOX nanocomplexes induced more apoptosis or necrosis. A temperature (69% release after 48 h)- and pH (70% release after 48 h)-dependent DOX release was observed, whereby more DOX was released at a high temperature of 42 C and pH value of 5.4. Thus, the developed nanocarriers possess great potential for use in the targeted delivery of conventional chemotherapeutic drugs with enhanced efficiency.
Keywords:Drug/targeted delivery;pH-/thermo-responsive;Magnetic mesoporous nanocarriers;Doxorubicin;Hepatocellular carcinoma
  1. Ryabchikova E, Adv. Nanomater. Biomed., 11, 118 (2021)
  2. Chiozzi V, Rossi F, Nanoscale Adv., 2, 5090 (2020).
  3. Foulkes R, Man E, Thind J, Yeung S, Joy A, Hoskins C, Biomater. Sci., 8, 4653 (2020)
  4. Seigneuric R, Markey L, Nuyten DSA, Dubernet C, Evelo CTA, Finot E, Garrido C, Curr. Mol. Med., 10, 640 (2010)
  5. Patra JK, Das G, Fraceto LF, Campos EVR, del Pilar Rodriguez-Torres M, et al., J. Nanobiotechnol., 16, 71 (2018)
  6. Mdlovu NV, Lin KS, Mavuso FA, Weng MT, J. Taiwan Inst. Chem. E, 117, 190 (2020)
  7. Mdlovu NV, Lin KS, Chen Y, Juang RS, Chang TW, Mdlovu NB, J. Taiwan Inst. Chem. E., 104, 260 (2019)
  8. Pardo A, Gomez-Florit M, Barbosa S, Taboada P, Domingues RM, Gomes RE, ACS Nano, 15, 175 (2021)
  9. Wu Y, Lu Z, Li Y, Yang J, Zhang X, Nanomaterials, 10, 1441 (2020)
  10. Dehvari K, Chen Y, Tsai YH, Tseng SH, Lin SK, J. Biomed. Nanotechnol., 12, 1734 (2016)
  11. Szczesniak B, Choma J, Jaroniec M, Chem. Commun. (2020).
  12. Rasmussen MK, Bordallo HN, Bordenalli MA, Akamatsu MA, Trezena AG, et al., Microporous Mesoporous Mater., 312, 110763 (2021)
  13. Khabazipour M, Shariati S, Safa F, Synth. React. Inorg. Met.-Org. Nano-Metal Chem., 46, 759 (2016).
  14. Yan J, Xu X, Zhou J, Liu C, Zhang L, Wang D, Yang F, Zhang H, ACS Appl. Bio Mater., 3, 1216 (2020)
  15. Mdlovu NV, Mavuso FA, Lin KS, Chang TW, Chen Y, Wang SSS, Wu CM, Mdlovu NB, Lin YS, Colloids Surf. A: Physicochem. Eng. Asp., 562, 361 (2019)
  16. Heggannavar GB, Hiremath CG, Achari DD, Pangarkar VG, Kariduraganavar MY, ACS Omega, 3, 8017 (2018)
  17. Abdelhameed RM, Alzahrani E, Shaltout AA, Emam HE, J. Ind. Eng. Chem., 94, 134 (2021)
  18. Wild CP, Weiderpass E, Stewart BW, International Agency for Research on Cancer, Lyon, pp.22 2020.
  19. World Health Organization, World health statistics 2019: monitoring health for the SDGs, sustainable development goals (2019).
  20. Lin L, Yan L, Liu Y, Qu C, Ni J, Li H, Liver Cancer, 9, 563 2020.
  21. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jema A, CA Cancer J. Clin., 68, 394 (2018)
  22. Daher S, Massarwa M, Benson AA, Khoury T, J. Clin. Transl. Hepatol., 6, 69 (2018)
  23. Jeong CU, Kim JH, Kim YC, J. Ind. Eng. Chem., 87, 187 (2020)
  24. Guo Y, Lee H, Jeong H, Prog. Mol. Biol. Transl. Sci., 171, 61 (2020)
  25. Luo D, Carter KA, Razi A, Geng J, Shao S, Giraldo D, Sunar U, Ortega J, Biomaterials, 75, 193 (2016)
  26. Rahman HS, Othman HH, Hammadi N, Yeap SK, Amin KM, Samad NA, Alitheen NB, Int. J. Nanomedicine, 15, 2439 (2020)
  27. Kanwal U, Irfan Bukhari N, Ovais M, Abass N, Hussain K, Raza A, J. Drug Target., 26, 296 (2018)
  28. Singh AP, Biswas A, Shukla A, Maiti P, Target. Ther., 4, 1 (2019)
  29. Jin MZ, Jin WL, Signal Transduct. Target. Ther., 5, 1 (2020)
  30. Schmidt CK, Medina-Sanchez M, Edmondson RJ, Schmidt OG, Nat. Commun., 11, 1 (2020)
  31. Fang CY, Wu CC, Fang CL, Chen WY, Chen CL, PLoS ONE, 12 (2017)
  32. Barnabas MJ, Parambadath S, Ha CS, J. Ind. Eng. Chem., 53, 392 (2017)
  33. Albayati TM, Abd Alkadir AJ, J. Drug Deliv Sci. Technol., 53 (2019)
  34. Kumar K, Siril KS, Javid B, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 69, 1335 (2016)
  35. Kumar R, Singh A, Garg N, Siril PF, Ultrason. Sonochem., 40, 686 (2018)
  36. Kumar R, Singh A, Garg N, J. Drug Deliv. Sci. Technol., 54, 101277 (2019)
  37. Takata S, Suzuki J, Shinohara T, Oku T, Tominaga T, Ohishi K, Iwase H, et al., JPS Conf. Proc., 8 (2015)
  38. Hoshyar N, Gray S, Han H, Bao G, Nanomedicine, 11, 673 (2016)
  39. Fritzen DL, Giordano L, Rodrigues L, Monteiro JH, Nanomaterials, 10, 2015 (2020)
  40. Vargas-Osorio Z, Gonzalez-Gomez MA, Pineiro Y, Vazquez-Vazquez C, et al., J. Mater. Chem. B, 5, 9395 (2017)
  41. Chander V, Gangenahalli G, Sci. Rep., 10, 1 (2020)
  42. Mdlovu NV, Chen Y, Lin KS, Hsu MW, Wang SSS, Wu CM, Lin YS, Ohishi K, J. Taiwan Inst. Chem. E., 96, 526 (2019)
  43. Lothenbach B, Durdzinski P, De Weerdt K, Thermogravimetric analysis. a practical guide to microstructural analysis of cementitious materials (1st ed.). 2016.
  44. Zid L, Zelenak V, Girman V, Bednarcik J, et al., RSC Adv., 10, 15825 (2020)
  45. Iacovita C, Stiufiuc GF, Dudric R, Vedeanu N, Tetean R, Stiufiuc RI, Lucaciu CM, Magnetochemistry, 6, 23 (2020)
  46. Kafrouni L, Savadogo O, Prog. Biomater., 5, 147 (2016)
  47. Mody VV, Singh A, Wesley B, Eur. J. Nanomed., 5, 11 (2013)
  48. Mdlovu NV, Lin KS, Chen Y, Wu CM, Colloids Surf. A: Physicochem. Eng. Asp., 615 (2021)
  49. Philippova O, Barabanova A, Molchanov V, Khokhlov A, Eur. Polym. J., 47, 542 (2011)
  50. Modak AK, Barui CR, Patra A, Bhaumik A, Chem. Commun., 49, 7644 (2013)
  51. Hrubovcak P, Kucerka N, Zelenakova A, Zelenak V, Acta Phys. Pol. A, 137, 730 (2020)
  52. Liu Y, Tan J, Thomas A, Ou-Yang D, Muzykantov VR, Ther. Deliv., 3, 181 (2012)
  53. Ki MR, Kim JK, Kim SH, Nguyen TKM, Kim KH, Pack SP, J. Ind. Eng. Chem., 81, 367 (2020)
  54. Tawfik SM, Sharipov M, Huy BT, Gerelkhuu Z, Biechele-Speziale D, Lee YI, J. Ind. Eng. Chem., 57, 424 (2018)
  55. Xu HL, Mao KL, Huang YP, Yang JJ, Xu J, Chen PP, Fan ZL, Zou S, Gao ZZ, Yin JY, Xiao J, Nanoscale, 8, 14222 (2016)
  56. Wang H, Ellipilli S, Lee WJ, Li X, Vieweger M, Ho YS, Guo P, J. Control. Release, 330, 173 (2020)
  57. Bandiera S, Pfeffer S, Baumert TF, Zeisel MB, J. Hepatol., 62, 448 (2015)
  58. Mishra S, Manna K, Kayal U, Saha M, Chatterjee S, Chandra D, et al., RSC Adv., 10, 23148 (2020)