Electrohydrodynamically Atomized pH-Responsive PLGA/ZnO Quantum Dots for Local Delivery in Lung Cancer

Hyeon Beom Kim; Nileshkumar Meghani; Miyoung Park; Sang Ho Lee; Sun Ryung Lee; Young-Jae Cho; Yang Hoi Doh; Kyung Hyun Choi

Macromolecular Research, Vol.28, No.4, 407-414, April, 2020

DOI10.1007/s13233-020-8053-9 Export Citation

Electrohydrodynamically Atomized pH-Responsive PLGA/ZnO Quantum Dots for Local Delivery in Lung Cancer

Hyeon Beom Kim¹, Nileshkumar Meghani², Miyoung Park³, Sang Ho Lee³, Sun Ryung Lee⁴, Young-Jae Cho^{2, 5}, Yang Hoi Doh^{6, †}, and Kyung Hyun Choi²

¹Korea Institute of Industrial Technology, 102 Jejudaehak-ro, Jeju 63243, Korea
²Department of Mechatronics Engineering, Jeju National University, Jeju 63243, Korea
³Korea Evaluation Institute of Industrial Technology, 32, Cheomdan-ro 8 Gil, Dong-gu, Daegu 41069, Korea
⁴Department of Biology, Jeju National University, Jeju 63243, Korea
⁵Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi 13620, Korea
⁶Department of Electronics Engineering, Jeju National University, Jeju 63243, Korea

E-mail:

Targeted drug delivery to cancerous tissues using nanomaterials is a challenging task that is fast gaining attention. Here, we report the fabrication of ZnO quantum dots (QDs) encapsulated in the biodegradable copolymer poly(DL-lactide-co-glycolide) (PLGA) nanoparticles using an electrohydrodynamic atomization process to enhance cytotoxicity against the metastatic cancer A549 cell line. The encapsulation and the small size increased the cellular uptake of the PLGA/ZnO QDs. Furthermore, the PLGA/ZnO QDs are pH-responsive and can therefore target cancerous cells based on the acidic tumor microenvironment, leaving healthy cells less affected. PLGA/ZnO QDs induced cell death and obstructed cell invasion and migration at low concentrations (7.5 μg/mL). We verified these activities through thiazolyl blue, tetrazolium blue (MTT), scratch assay, and clonogenic assays on metastatic A549 cells, with normal human lung cells, Human Small Airway Epithelia Cells (SAECs) as the controls. Thus, PLGA-encapsulated ZnO QDs, owing to their selective localization, ability to enter cells, cytotoxicity, and retention effect, could provide a potential platform for tumor-directed drug therapy.

Keywords:electrohydrodynamic atomization;PLGA/ZnO QDs;cytotoxicity;controlled drug delivery;pH responsive;lung cancer

[References]

Han Z, Wang X, Heng C, Han Q, Cai S, Li J, Qi C, Liang W, Yang R, Wang C, Phys. Chem. Chem. Phys., 17, 21576 (2015)
Danhier F, Feron O, Preat V, J. Control. Release, 148, 135 (2010)
Cruz CSD, Tanoue LT, Matthay RA, Clin. Chest Med., 32, 605 (2011)
Wong MCS, Lao XQ, Ho KF, Goggins WB, Tse SLA, Sci. Rep., 7, 14300 (2017)
Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC, Chest, 143, e278S (2013)
Menon JU, Kuriakose A, Iyer R, Hernandez E, Gandee L, Zhang S, Takahashi M, Zhang Z, Saha D, Nguyen KT, Sci. Rep., 7, 13249 (2017)
Al-Jamal WT, Kostarelos K, Accounts Chem. Res., 44, 1094 (2011)
Liang P, Liu CJ, Zhuo RX, Cheng SX, J. Mater. Chem. B, 1, 4243 (2013)
Amin HH, Meghani NM, Oh KT, Chio H, Lee BJ, J. Drug Deliv. Sci. Technol., 41, 222 (2017)
Gulzar A, Gai S, Yang P, Li C, Ansari MB, Lin J, J. Mater. Chem. B, 3, 8599 (2015)
Mura S, Nicolas J, Couvreur P, Nat. Mater., 12(11), 991 (2013)
Amin HH, Meghani NM, Park C, Nguyen VH, Tran TTD, Tran PHL, Lee BJ, Colloids Surf. B: Biointerfaces, 159, 571 (2017)
Gao W, Chan JM, Farokhzad OC, Mol. Pharm., 7, 1913 (2010)
Shin JY, Yang Y, Heo P, Lee JC, Kong B, Cho JY, Yoon K, Shin CS, Seo JH, Kim SG, Int. J. Nanomedicine, 7, 2805 (2012)
Zhao J, Yang H, Li J, Wang Y, Wang X, Sci. Rep., 7, 18014 (2017)
Hu G, Cai Y, Tu Z, Luo J, Qiao X, Chen Q, Zhang W, RSC Adv, 5, 82050 (2015)
Wang Z, Qiao R, Tang N, Lu Z, Wang H, Zhang Z, Xue X, Huang Z, Zhang X, Zhang G, Li Y, Biomaterials, 127, 25 (2017)
Xu P, Wang R, Ouyang J, Chen B, Nanoscale Res. Lett., 10, 94 (2015)
Roshini A, Jagadeesan S, Cho YJ, Lim JH, Choi KH, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 81, 551 (2017)
Krishna PG, Ananthaswamy PP, Yadavalli T, Mutta NB, Sannaiah A, Shivanna Y, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 62, 919 (2016)
Senapati S, Mahanta AK, Kumar S, Maiti P, Signal Transduct. Target. Ther., 3, 7 (2018)
Hanley C, Layne J, Punnoose A, Reddy K, Coombs I, Combs A, Feris K, Wingett D, Nanotechnology, 19, 295103 (2008)
Ostrovsky S, Kazimirsky G, Gedanken A, Brodie C, Nano Res., 2, 882 (2009)
Lipovsky A, Tzitrinovich Z, Friedmann H, Applerot G, Gedanken A, Lubart R, J. Phys. Chem. C, 113, 15997 (2009)
Fakhar-e-Alam M, Rahim S, Atif M, Aziz MH, Malick MI, Zaidi S, Suleman R, Majid A, Laser. Phys. Lett., 11, 025601 (2013)
Liu L, Zhang J, Su X, Mason RP, J. Biomed. Nanotechnol., 4, 524 (2008)
Shivaji K, Mani S, Ponmurugan P, De Castro CS, Davies ML, Balasubramanian MG, Pitchaimuthu S, ACS Appl. Nano Mater., 1, 1683 (2018)
Yong KT, Wang Y, Roy I, Rui H, Swihart MT, Law WC, Kwak SK, Ye L, Liu J, Mahajan SD, Reynolds JL, Theranostics, 2, 681 (2012)
Muhammad F, Guo M, Guo Y, Qi W, Qu F, Sun F, Zhao H, Zhu G, J. Mater. Chem., 21, 13406 (2011)
Prabhakaran MP, Zamani M, Felice B, Ramakrishna S, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 56, 66 (2015)
Meghani NM, Amin HH, Park C, Park JB, Cui JH, Cao QR, Lee BJ, Int. J. Pharm., 545, 101 (2018)
Parhizkark M, Reardon PJ, Knowles JC, Browning RJ, Stride E, Barbara PR, Harker AH, Edirisinghe M, Nanomedicine, 12, 1919 (2016)
Xie J, Marijnissen JC, Wang CH, Biomaterials, 27, 3321 (2006)
Naraharisetti PK, Ong BYS, Xie JW, Lee TKY, Wang CH, Sahinidis NV, Biomaterials, 28, 886 (2007)
Cavalli R, Bisazza A, Bussano R, Trotta M, Civra A, Lembo D, Ranucci E, Ferruti P, J. Drug Deliv., 2011 (2011).
Cai X, Luo Y, Zhang W, Du D, Lin Y, ACS Appl. Mater. Interfaces, 8, 22442 (2016)
Pan C, Liu Y, Zhou M, Wang W, Shi M, Xing M, Liao W, Int. J. Nanomedicine, 13, 1119 (2018)
Yilmaz G, Guler E, Geyik C, Demir B, Ozkan M, Demirkol DO, Ozcelik S, Timur S, Becer CR, Mol. Syst. Des. Eng., 3, 150 (2018)
Yao Y, Saw PE, Nie Y, Wong PP, Jiang L, Ye X, Chen J, Ding T, Xu L, Yao H, J. Mater. Chem. B, 7, 576 (2019)

[1] Han Z, Wang X, Heng C, Han Q, Cai S, Li J, Qi C, Liang W, Yang R, Wang C, Phys. Chem. Chem. Phys., 17, 21576 (2015)

[2] Danhier F, Feron O, Preat V, J. Control. Release, 148, 135 (2010)

[3] Cruz CSD, Tanoue LT, Matthay RA, Clin. Chest Med., 32, 605 (2011)

[4] Wong MCS, Lao XQ, Ho KF, Goggins WB, Tse SLA, Sci. Rep., 7, 14300 (2017)

[5] Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC, Chest, 143, e278S (2013)

[6] Menon JU, Kuriakose A, Iyer R, Hernandez E, Gandee L, Zhang S, Takahashi M, Zhang Z, Saha D, Nguyen KT, Sci. Rep., 7, 13249 (2017)

[7] Al-Jamal WT, Kostarelos K, Accounts Chem. Res., 44, 1094 (2011)

[8] Liang P, Liu CJ, Zhuo RX, Cheng SX, J. Mater. Chem. B, 1, 4243 (2013)

[9] Amin HH, Meghani NM, Oh KT, Chio H, Lee BJ, J. Drug Deliv. Sci. Technol., 41, 222 (2017)

[10] Gulzar A, Gai S, Yang P, Li C, Ansari MB, Lin J, J. Mater. Chem. B, 3, 8599 (2015)

[11] Mura S, Nicolas J, Couvreur P, Nat. Mater., 12(11), 991 (2013)

[12] Amin HH, Meghani NM, Park C, Nguyen VH, Tran TTD, Tran PHL, Lee BJ, Colloids Surf. B: Biointerfaces, 159, 571 (2017)

[13] Gao W, Chan JM, Farokhzad OC, Mol. Pharm., 7, 1913 (2010)

[14] Shin JY, Yang Y, Heo P, Lee JC, Kong B, Cho JY, Yoon K, Shin CS, Seo JH, Kim SG, Int. J. Nanomedicine, 7, 2805 (2012)

[15] Zhao J, Yang H, Li J, Wang Y, Wang X, Sci. Rep., 7, 18014 (2017)

[16] Hu G, Cai Y, Tu Z, Luo J, Qiao X, Chen Q, Zhang W, RSC Adv, 5, 82050 (2015)

[17] Wang Z, Qiao R, Tang N, Lu Z, Wang H, Zhang Z, Xue X, Huang Z, Zhang X, Zhang G, Li Y, Biomaterials, 127, 25 (2017)

[18] Xu P, Wang R, Ouyang J, Chen B, Nanoscale Res. Lett., 10, 94 (2015)

[19] Roshini A, Jagadeesan S, Cho YJ, Lim JH, Choi KH, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 81, 551 (2017)

[20] Krishna PG, Ananthaswamy PP, Yadavalli T, Mutta NB, Sannaiah A, Shivanna Y, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 62, 919 (2016)

[21] Senapati S, Mahanta AK, Kumar S, Maiti P, Signal Transduct. Target. Ther., 3, 7 (2018)

[22] Hanley C, Layne J, Punnoose A, Reddy K, Coombs I, Combs A, Feris K, Wingett D, Nanotechnology, 19, 295103 (2008)

[23] Ostrovsky S, Kazimirsky G, Gedanken A, Brodie C, Nano Res., 2, 882 (2009)

[24] Lipovsky A, Tzitrinovich Z, Friedmann H, Applerot G, Gedanken A, Lubart R, J. Phys. Chem. C, 113, 15997 (2009)

[25] Fakhar-e-Alam M, Rahim S, Atif M, Aziz MH, Malick MI, Zaidi S, Suleman R, Majid A, Laser. Phys. Lett., 11, 025601 (2013)

[26] Liu L, Zhang J, Su X, Mason RP, J. Biomed. Nanotechnol., 4, 524 (2008)

[27] Shivaji K, Mani S, Ponmurugan P, De Castro CS, Davies ML, Balasubramanian MG, Pitchaimuthu S, ACS Appl. Nano Mater., 1, 1683 (2018)

[28] Yong KT, Wang Y, Roy I, Rui H, Swihart MT, Law WC, Kwak SK, Ye L, Liu J, Mahajan SD, Reynolds JL, Theranostics, 2, 681 (2012)

[29] Muhammad F, Guo M, Guo Y, Qi W, Qu F, Sun F, Zhao H, Zhu G, J. Mater. Chem., 21, 13406 (2011)

[30] Prabhakaran MP, Zamani M, Felice B, Ramakrishna S, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 56, 66 (2015)

[31] Meghani NM, Amin HH, Park C, Park JB, Cui JH, Cao QR, Lee BJ, Int. J. Pharm., 545, 101 (2018)

[32] Parhizkark M, Reardon PJ, Knowles JC, Browning RJ, Stride E, Barbara PR, Harker AH, Edirisinghe M, Nanomedicine, 12, 1919 (2016)

[33] Xie J, Marijnissen JC, Wang CH, Biomaterials, 27, 3321 (2006)

[34] Naraharisetti PK, Ong BYS, Xie JW, Lee TKY, Wang CH, Sahinidis NV, Biomaterials, 28, 886 (2007)

[35] Cavalli R, Bisazza A, Bussano R, Trotta M, Civra A, Lembo D, Ranucci E, Ferruti P, J. Drug Deliv., 2011 (2011).

[36] Cai X, Luo Y, Zhang W, Du D, Lin Y, ACS Appl. Mater. Interfaces, 8, 22442 (2016)

[37] Pan C, Liu Y, Zhou M, Wang W, Shi M, Xing M, Liao W, Int. J. Nanomedicine, 13, 1119 (2018)

[38] Yilmaz G, Guler E, Geyik C, Demir B, Ozkan M, Demirkol DO, Ozcelik S, Timur S, Becer CR, Mol. Syst. Des. Eng., 3, 150 (2018)

[39] Yao Y, Saw PE, Nie Y, Wong PP, Jiang L, Ye X, Chen J, Ding T, Xu L, Yao H, J. Mater. Chem. B, 7, 576 (2019)