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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Chloroquine Assisted Delivery of microRNA Mimic Let-7b to NSCLC Cell Line by PAMAM (G5) - HA Nano-Carrier

Author(s): Niloufar Maghsoudnia, Reza Baradaran Eftekhari, Alireza Naderi Sohi and Farid Abedin Dorkoosh*

Volume 18, Issue 1, 2021

Published on: 04 August, 2020

Page: [31 - 43] Pages: 13

DOI: 10.2174/1567201817666200804105017

Price: $65

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Abstract

Aim: Polyamidoamine (PAMAM) dendrimers are attracting interest of the scientists as vehicles for nucleic acid delivery due to their suitable properties. The highly positive surface charged of PAMAM enables an adequate interaction with negatively charged microRNAs.

Purpose: The purpose of this study is to investigate the anti-tumor effect of microRNA Mimic let-7b loaded in PAMAM dendrimers (G5) on Non-Small Cell Lung Cancer (NSCLC) cells.

Objective: In order to increase the anti-tumor effect, chloroquine is employed to enhance the endosomal escape which is counted as a limitation in the advancement of gene delivery. Nanoparticles (NPs) were coated with natural polysaccharide "Hyaluronic Acid (HA)" to develop biodegradable carriers with targeting moiety for over-expressed CD44 receptors on NSCLC cells. The size and zeta potential measurements, gel retardation, cellular uptake, cell viability and gene expression studies were investigated for the designed delivery system.

Results: DLS analysis showed monodispersed small nanoparticles, which was in agreement with TEM results. Remarkably, NPs in the cells pretreated with chloroquine exhibited the highest cytotoxicity and were capable of inducing apoptosis. In cellular uptake study, NPs labeled with Fluorescein Isothiocyanate (FITC), were successfully taken up in cancer cells. Moreover, the expression study of three genes linked with cancer initiation and development in NSCLC, including KRAS, p-21, and BCL-2 indicated a decrease in KRAS and BCL-2 (oncogenic and anti-apoptotic genes) and increase in p-21 (apoptotic gene).

Conclusion: All factors considered, the results declare that application of let-7b-loaded PAMAM-HA NPs in combination with chloroquine can be a promising therapeutic option in cancer cells inhibition. This fact has frequently been highlighted by many researchers upon the potentials of micro RNA delivery in cancer cells.

Keywords: Gene-delivery, NSCLC, PAMAM dendrimers, microRNA let-7b, chloroquine, cancer cells.

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[1]
Eftekhari, R.B.; Maghsoudnia, N.; Samimi, S.; Zamzami, A.; Dorkoosh, F.A. Co-delivery nanosystems for cancer treatment: a review. Pharm. Nanotechnol., 2019, 7(2), 90-112.
[http://dx.doi.org/10.2174/2211738507666190321112237] [PMID: 30907329]
[2]
Johnson, S.M.; Grosshans, H.; Shingara, J.; Byrom, M.; Jarvis, R.; Cheng, A.; Labourier, E.; Reinert, K.L.; Brown, D.; Slack, F.J. RAS is regulated by the let-7 microRNA family. Cell, 2005, 120(5), 635-647.
[http://dx.doi.org/10.1016/j.cell.2005.01.014] [PMID: 15766527]
[3]
Yu, F.; Yao, H.; Zhu, P.; Zhang, X.; Pan, Q.; Gong, C.; Huang, Y.; Hu, X.; Su, F.; Lieberman, J.; Song, E. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell, 2007, 131(6), 1109-1123.
[http://dx.doi.org/10.1016/j.cell.2007.10.054] [PMID: 18083101]
[4]
Zhao, Y.; Deng, C.; Wang, J.; Xiao, J.; Gatalica, Z.; Recker, R.R.; Xiao, G.G. Let-7 family miRNAs regulate estrogen receptor alpha signaling in estrogen receptor positive breast cancer. Breast Cancer Res. Treat., 2011, 127(1), 69-80.
[http://dx.doi.org/10.1007/s10549-010-0972-2] [PMID: 20535543]
[5]
(a)Akao, Y.; Nakagawa, Y.; Naoe, T. let-7 microRNA functions as a potential growth suppressor in human colon cancer cells. Biol. Pharm. Bull., 2006, 29(5), 903-906.
[http://dx.doi.org/10.1248/bpb.29.903] [PMID: 16651716]
(b)Kumar, M.S.; Erkeland, S.J.; Pester, R.E.; Chen, C.Y.; Ebert, M.S.; Sharp, P.A.; Jacks, T. Suppression of non-small cell lung tumor development by the let-7 microRNA family. Proc. Natl. Acad. Sci. USA, 2008, 105(10), 3903-3908.
[http://dx.doi.org/10.1073/pnas.0712321105] [PMID: 18308936]
[6]
Trang, P.; Medina, P.P.; Wiggins, J.F.; Ruffino, L.; Kelnar, K.; Omotola, M.; Homer, R.; Brown, D.; Bader, A.G.; Weidhaas, J.B.; Slack, F.J. Regression of murine lung tumors by the let-7 microRNA. Oncogene, 2010, 29(11), 1580-1587.
[http://dx.doi.org/10.1038/onc.2009.445] [PMID: 19966857]
[7]
Johnson, C.D.; Esquela-Kerscher, A.; Stefani, G.; Byrom, M.; Kelnar, K.; Ovcharenko, D.; Wilson, M.; Wang, X.; Shelton, J.; Shingara, J.; Chin, L.; Brown, D.; Slack, F.J. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res., 2007, 67(16), 7713-7722.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1083] [PMID: 17699775]
[8]
Esquela-Kerscher, A.; Trang, P.; Wiggins, J.F.; Patrawala, L.; Cheng, A.; Ford, L.; Weidhaas, J.B.; Brown, D.; Bader, A.G.; Slack, F.J. The let-7 microRNA reduces tumor growth in mouse models of lung cancer. Cell Cycle, 2008, 7(6), 759-764.
[http://dx.doi.org/10.4161/cc.7.6.5834] [PMID: 18344688]
[9]
Chen, Y.; Gao, D-Y.; Huang, L. In vivo delivery of miRNAs for cancer therapy: challenges and strategies. Adv. Drug Deliv. Rev., 2015, 81, 128-141.
[http://dx.doi.org/10.1016/j.addr.2014.05.009] [PMID: 24859533]
[10]
Zhang, Y.; Wang, Z.; Gemeinhart, R.A. Progress in microRNA delivery. J. Control. Release, 2013, 172(3), 962-974.
[http://dx.doi.org/10.1016/j.jconrel.2013.09.015] [PMID: 24075926]
[11]
Baradaran Eftekhari, R.; Maghsoudnia, N.; Dorkoosh, F.A. Chloroquine: a brand-new scenario for an old drug. Expert Opin. Drug Deliv., 2020, 17(3), 275-277.
[http://dx.doi.org/10.1080/17425247.2020.1716729] [PMID: 31951752]
[12]
Janku, F.; McConkey, D.J.; Hong, D.S.; Kurzrock, R. Autophagy as a target for anticancer therapy. Nat. Rev. Clin. Oncol., 2011, 8(9), 528-539.
[http://dx.doi.org/10.1038/nrclinonc.2011.71] [PMID: 21587219]
[13]
King, M.A.; Ganley, I.G.; Flemington, V. Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene, 2016, 35(34), 4518-4528.
[http://dx.doi.org/10.1038/onc.2015.511] [PMID: 26853465]
[14]
Balic, A.; Sørensen, M.D.; Trabulo, S.M.; Sainz, B., Jr; Cioffi, M.; Vieira, C.R.; Miranda-Lorenzo, I.; Hidalgo, M.; Kleeff, J.; Erkan, M.; Heeschen, C. Chloroquine targets pancreatic cancer stem cells via inhibition of CXCR4 and hedgehog signaling. Mol. Cancer Ther., 2014, 13(7), 1758-1771.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0948] [PMID: 24785258]
[15]
Pathways, M. Targeting the CXCR4-CXCL12 axis-untapped potential in the tumor microenvironment Scala, Stefania. Clin. Cancer Res., 2015, 21(19), 4278-4285.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0914] [PMID: 26199389]
[16]
(a)Öztuna, A.; Nazır, H. In vitro transfection potential of fluorinated G5 PAMAM dendrimers for miRNA delivery to MRC-5 cells. Eur. Respir. J., 2018, 4(2), 92-100.
(b)Chen, W.; Liu, Y.; Liang, X.; Huang, Y.; Li, Q. Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.Acta Biomater, 2017.57, 238-250.
[http://dx.doi.org/10.1016/j.actbio.2017.05.030] [PMID: 28511876]
(c)Song, Z.; Liang, X.; Wang, Y.; Han, H.; Yang, J.; Fang, X.; Li, Q. Phenylboronic acid-functionalized polyamidoamine-mediated miR-34a delivery for the treatment of gastric cancer.Biomater. Sci., 2019,7(4), 1632-1642.
[http://dx.doi.org/10.1039/C8BM01385C] [PMID: 30720809]
(d)Han, H.; Yang, J.; Wang, Y.; Chen, W.; Chen, J.; Yang, Y.; Li, Q. Nucleobase-modified polyamidoamine-mediated miR-23b delivery to inhibit the proliferation and migration of lung cancer. Biomater. Sci., 2017, 5(11), 2268-2275.
[http://dx.doi.org/10.1039/C7BM00599G] [PMID: 28976503]
[17]
(a)Han, M.; Lv, Q.; Tang, X-J.; Hu, Y.L.; Xu, D.H.; Li, F.Z.; Liang, W.Q.; Gao, J.Q. Overcoming drug resistance of MCF-7/ADR cells by altering intracellular distribution of doxorubicin via MVP knockdown with a novel siRNA polyamidoamine-hyaluronic acid complex. J. Control. Release, 2012, 163(2), 136-144..
[http://dx.doi.org/10.1016/j.jconrel.2012.08.020] [PMID: 22940126]
(b)Urbiola, K.; Sanmartín, C.; Blanco-Fernández, L.; Tros de Ilarduya, C. Efficient targeted gene delivery by a novel PAMAM/DNA dendriplex coated with hyaluronic acid. Nanomedicine, 2014, 9(18), 2787-2801.
[http://dx.doi.org/10.2217/nnm.14.45] [PMID: 24959932]
[18]
(a)Wu, J.; Deng, C.; Meng, F.; Zhang, J.; Sun, H.; Zhong, Z. Hyaluronic acid coated PLGA nanoparticulate docetaxel effectively targets and suppresses orthotopic human lung cancer. J. Control. Release, 2017, 259, 76-82.
[http://dx.doi.org/10.1016/j.jconrel.2016.12.024] [PMID: 28027947]
(b)Ravar, F.; Saadat, E.; Gholami, M.; Dehghankelishadi, P.; Mahdavi, M.; Azami, S.; Dorkoosh, F.A. Hyaluronic acid-coated liposomes for targeted delivery of paclitaxel, in-vitro characterization and in-vivo evaluation. J. Control. Release, 2016, 229, 10-22.
[http://dx.doi.org/10.1016/j.jconrel.2016.03.012] [PMID: 26968799]
[19]
Qi, X.; Fan, Y.; He, H.; Wu, Z. Hyaluronic acid-grafted polyamidoamine dendrimers enable long circulation and active tumor targeting simultaneously. Carbohydr. Polym., 2015, 126, 231-239.
[http://dx.doi.org/10.1016/j.carbpol.2015.03.019] [PMID: 25933544]
[20]
Jevprasesphant, R.; Penny, J.; Jalal, R.; Attwood, D.; McKeown, N.B.; D’Emanuele, A. The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int. J. Pharm., 2003, 252(1-2), 263-266.
[http://dx.doi.org/10.1016/S0378-5173(02)00623-3] [PMID: 12550802]
[21]
(a)Yang, W.; Cheng, Y.; Xu, T.; Wang, X.; Wen, L.P. Targeting cancer cells with biotin-dendrimer conjugates., Eur. J. Med. Chem., 2009, 44(2), 862-868.
[http://dx.doi.org/10.1016/j.ejmech.2008.04.021] [PMID: 18550227]
(b)Denora, N.; Laquintana, V.; Lopalco, A.; Iacobazzi, R.M.; Lopedota, A.; Cutrignelli, A.; Iacobellis, G.; Annese, C.; Cascione, M.; Leporatti, S.; Franco, M. In vitro targeting and imaging the translocator protein TSPO 18-kDa through G(4)-PAMAM-FITC labeled dendrimer. J. Control. Release, 2013, 172(3), 1111-1125.
[http://dx.doi.org/10.1016/j.jconrel.2013.09.024] [PMID: 24096015]
[22]
(a)Shadrack, D.M.; Mubofu, E.B.; Nyandoro, S.S. Synthesis of polyamidoamine dendrimer for encapsulating tetramethylscutellarein for potential bioactivity enhancement., Int. J. Mol. Sci., 2015, 16(11), 26363-26377..
[http://dx.doi.org/10.3390/ijms161125956] [PMID: 26556337]
(b)Ma, P.; Zhang, X.; Ni, L.; Li, J.; Zhang, F.; Wang, Z.; Lian, S.; Sun, K. Targeted delivery of polyamidoamine-paclitaxel conjugate functionalized with anti-human epidermal growth factor receptor 2 trastuzumab. Int. J. Nanomedicine, 2015, 10, 2173-2190.
[http://dx.doi.org/10.2147/IJN.S77152] [PMID: 25834432]
[23]
Oddone, N.; Zambrana, A.I.; Tassano, M.; Porcal, W.; Cabral, P.; Benech, J.C. Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells. J. Nanopart. Res., 2013, 15(7), 1776.
[http://dx.doi.org/10.1007/s11051-013-1776-1]
[24]
Ciftci, K.; Levy, R.J. Enhanced plasmid DNA transfection with lysosomotropic agents in cultured fibroblasts. Int. J. Pharm., 2001, 218(1-2), 81-92.
[http://dx.doi.org/10.1016/S0378-5173(01)00623-8] [PMID: 11337152]
[25]
(a)Sherr, C.J. Acquired palbociclib resistance in KRAS-mutant lung cancer. Oncotarget, 2018, 9(67), 32734-32735..
[http://dx.doi.org/10.18632/oncotarget.26027] [PMID: 30214680]
(b)Bahcall, M.; Awad, M.M.; Sholl, L.M.; Wilson, F.H.; Xu, M.; Wang, S.; Palakurthi, S.; Choi, J.; Ivanova, E.V.; Leonardi, G.C.; Ulrich, B.C.; Paweletz, C.P.; Kirschmeier, P.T.; Watanabe, M.; Baba, H.; Nishino, M.; Nagy, R.J.; Lanman, R.B.; Capelletti, M.; Chambers, E.S.; Redig, A.J.; VanderLaan, P.A.; Costa, D.B.; Imamura, Y.; Jänne, P.A. Amplification of wild-type KRAS imparts resistance to crizotinib in MET exon 14 mutant non-small cell lung cancer., Clin. Cancer Res.,2018, 24(23), 5963-5976..
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0876] [PMID: 30072474]
(c)Suzawa, K.; Offin, M.; Lu, D.; Kurzatkowski, C.; Vojnic, M.; Smith, R.S.; Sabari, J.K.; Tai, H.; Mattar, M.; Khodos, I.; de Stanchina, E.; Rudin, C.M.; Kris, M.G.; Arcila, M.E.; Lockwood, W.W.; Drilon, A.; Ladanyi, M.; Somwar, R. Activation of KRAS mediates resistance to targeted therapy in MET exon 14-mutant non-small cell lung cancer. Clin. Cancer Res., 2019, 25(4), 1248-1260..
[http://dx.doi.org/10.1158/1078-0432.CCR-18-1640] [PMID: 30352902]
(d)Braicu, C.; Gulei, D.; Cojocneanu, R.; Raduly, L.; Jurj, A.; Knutsen, E.; Calin, G.A.; Berindan-Neagoe, I. miR-181a/b therapy in lung cancer: reality or myth? Mol. Oncol., 2019, 13(1), 9-25..
[http://dx.doi.org/10.1002/1878-0261.12420] [PMID: 30548184]
(e)Zhang, M.L.; Nie, F.Q.; Sun, M.; Xia, R.; Xie, M.; Lu, K.H.; Li, W. HOXA5 indicates poor prognosis and suppresses cell proliferation by regulating p21 expression in non-small cell lung cancer., Tumour Biol., 2015, 36(5), 3521-3531.
[http://dx.doi.org/10.1007/s13277-014-2988-4] [PMID: 25549794]
(f)Pezzella, F.; Turley, H.; Kuzu, I.; Tungekar, M.F.; Dunnill, M.S.; Pierce, C.B.; Harris, A.; Gatter, K.C.; Mason, D.Y. bcl-2 protein in non-small-cell lung carcinoma. N. Engl. J. Med., 1993, 329(10), 690-694..
[http://dx.doi.org/10.1056/NEJM199309023291003] [PMID: 8393963]
(g)Gandhi, L.; Camidge, D.R.; Ribeiro de Oliveira, M.; Bonomi, P.; Gandara, D.; Khaira, D.; Hann, C.L.; McKeegan, E.M.; Litvinovich, E.; Hemken, P.M.; Dive, C.; Enschede, S.H.; Nolan, C.; Chiu, Y.L.; Busman, T.; Xiong, H.; Krivoshik, A.P.; Humerickhouse, R.; Shapiro, G.I.; Rudin, C.M. Phase I study of navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J. Clin. Oncol., 2011, 29(7), 909-916.
[http://dx.doi.org/10.1200/JCO.2010.31.6208] [PMID: 21282543]
[26]
Abedi-Gaballu, F.; Dehghan, G.; Ghaffari, M.; Yekta, R.; Abbaspour-Ravasjani, S.; Baradaran, B.; Dolatabadi, J.E.N.; Hamblin, M.R. PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy. Applied Mat. Today, 2018, 12, 177-190.
[http://dx.doi.org/10.1016/j.apmt.2018.05.002]
[27]
Hu, B.; Ma, Y.; Yang, Y.; Zhang, L.; Han, H.; Chen, J. CD44 promotes cell proliferation in non-small cell lung cancer. Oncol. Lett., 2018, 15(4), 5627-5633.
[http://dx.doi.org/10.3892/ol.2018.8051] [PMID: 29552200]
[28]
Vaidyanathan, S.; Anderson, K.B.; Merzel, R.L.; Jacobovitz, B.; Kaushik, M.P.; Kelly, C.N.; van Dongen, M.A.; Dougherty, C.A.; Orr, B.G.; Banaszak Holl, M.M. Quantitative measurement of cationic polymer vector and polymer-pDNA polyplex intercalation into the cell plasma membrane. ACS Nano, 2015, 9(6), 6097-6109.
[http://dx.doi.org/10.1021/acsnano.5b01263] [PMID: 25952271]
[29]
Kitchens, K.M.; Foraker, A.B.; Kolhatkar, R.B.; Swaan, P.W.; Ghandehari, H. Endocytosis and interaction of poly (amidoamine) dendrimers with Caco-2 cells. Pharm. Res., 2007, 24(11), 2138-2145.
[http://dx.doi.org/10.1007/s11095-007-9415-0] [PMID: 17701324]
[30]
Fox, L.J.; Richardson, R.M.; Briscoe, W.H. PAMAM dendrimer - cell membrane interactions. Adv. Colloid Interface Sci., 2018, 257, 1-18.
[http://dx.doi.org/10.1016/j.cis.2018.06.005] [PMID: 30008347]
[31]
Jeong, G-W.; Jeong, Y-I.; Nah, J-W. Triggered doxorubicin release using redox-sensitive hyaluronic acid-g-stearic acid micelles for targeted cancer therapy. Carbohydr. Polym., 2019, 209, 161-171.
[http://dx.doi.org/10.1016/j.carbpol.2019.01.018] [PMID: 30732795]
[32]
(a)Li, Y-F.; Zhang, H-T.; Xin, L. Hyaluronic acid-modified polyamidoamine dendrimer G5-entrapped gold nanoparticles delivering METase gene inhibits gastric tumor growth via targeting CD44+ gastric cancer cells. J. Cancer Res. Clin. Oncol., 2018, 144(8), 1463-1473.
[http://dx.doi.org/10.1007/s00432-018-2678-5] [PMID: 29858680]
(b)Kesharwani, P.; Xie, L.; Banerjee, S.; Mao, G.; Padhye, S.; Sarkar, F.H.; Iyer, A.K. Hyaluronic acid-conjugated polyamidoamine dendrimers for targeted delivery of 3,4-difluorobenzylidene curcumin to CD44 overexpressing pancreatic cancer cells. Colloids Surf. B Biointerfaces, 2015, 136, 413-423..
[http://dx.doi.org/10.1016/j.colsurfb.2015.09.043] [PMID: 26440757]
(c)Du, X.; Yin, S.; Wang, Y.; Gu, X.; Wang, G.; Li, J. Hyaluronic acid-functionalized half-generation of sectorial dendrimers for anticancer drug delivery and enhanced biocompatibility. Carbohydr. Polym., 2018, 202, 513-522.
[http://dx.doi.org/10.1016/j.carbpol.2018.09.015] [PMID: 30287030]
[33]
Paidikondala, M.; Rangasami, V.K.; Nawale, G.N.; Casalini, T.; Perale, G.; Kadekar, S.; Mohanty, G.; Salminen, T.; Oommen, O.P.; Varghese, O.P. Unexpected role of hyaluronic acid in trafficking siRNA across cellular barrier: first biomimetic, anionic, non‐viral transfection method. Angew. Chem. Int. Ed. Engl., 2019, 58(9), 2815-2819.
[http://dx.doi.org/10.1002/anie.201900099] [PMID: 30644615]
[34]
Yang, G.; Zhang, W.; Yu, C.; Ren, J.; An, Z. MicroRNA let-7: regulation, single nucleotide polymorphism, and therapy in lung cancer. J. Cancer Res. Ther., 2015, 11(Suppl. 1), C1-C6.
[http://dx.doi.org/10.4103/0973-1482.163830] [PMID: 26323902]
[35]
Castro, D.; Moreira, M.; Gouveia, A.M.; Pozza, D.H.; De Mello, R.A. MicroRNAs in lung cancer. Oncotarget, 2017, 8(46), 81679-81685.
[http://dx.doi.org/10.18632/oncotarget.20955] [PMID: 29113423]
[36]
(a)Dai, X.; Fan, W.; Wang, Y.; Huang, L.; Jiang, Y.; Shi, L.; Mckinley, D.; Tan, W.; Tan, C. Combined delivery of let-7b microRNA and paclitaxel via biodegradable nanoassemblies for the treatment of KRAS mutant cancer., Mol. Pharm., 2016, 13(2), 520-533.
[http://dx.doi.org/10.1021/acs.molpharmaceut.5b00756] [PMID: 26636714]
(b)Wu, M.; Wang, G.; Tian, W.; Deng, Y.; Xu, Y. MiRNA-based therapeutics for lung cancer. Curr. Pharm. Des., 2018, 23(39), 5989-5996.
[http://dx.doi.org/10.2174/1381612823666170714151715] [PMID: 28714413]
[37]
(a)Heiden, T.C.K.; Dengler, E.; Kao, W.J.; Heideman, W.; Peterson, R.E. Developmental toxicity of low generation PAMAM dendrimers in zebrafish., Toxicol. Appl. Pharmacol., 2007, 225(1), 70-79.
[http://dx.doi.org/10.1016/j.taap.2007.07.009] [PMID: 17764713]
(b)Fuchs, S.; Kapp, T.; Otto, H.; Schöneberg, T.; Franke, P.; Gust, R.; Schlüter, A.D. A surface-modified dendrimer set for potential application as drug delivery vehicles: synthesis, in vitro toxicity, and intracellular localization., Chemistry, 2004, 10(5), 1167-1192.
[http://dx.doi.org/10.1002/chem.200305386] [PMID: 15007808]
(c)Prieto, M.J.; Temprana, C.F.; del Río Zabala, N.E.; Marotta, C.H. Alonso, Sdel, V. Optimization and in vitro toxicity evaluation of G4 PAMAM dendrimer-risperidone complexes. Eur. J. Med. Chem., 2011, 46(3), 845-850.
[http://dx.doi.org/10.1016/j.ejmech.2010.12.021] [PMID: 21251731]
[38]
Baradaran Eftekhari, R.; Maghsoudnia, N.; Dorkoosh, F.A. Chloroquine: a brand-new scenario for an old drug; Taylor & Francis, 2020, pp. 275-277.
[39]
Sun, Y.; Liu, H.; Yang, T.; Lang, L.; Cheng, L.; Xing, H.; Yang, L.; Ding, P. Amphoteric poly(amido amine)s with adjustable balance between transfection efficiency and cytotoxicity for gene delivery. Colloids Surf. B Biointerfaces, 2019, 175, 10-17.
[http://dx.doi.org/10.1016/j.colsurfb.2018.11.045] [PMID: 30513469]
[40]
Verbaanderd, C.; Maes, H.; Schaaf, M.B.; Sukhatme, V.P.; Pantziarka, P.; Sukhatme, V.; Agostinis, P.; Bouche, G. Repurposing Drugs in Oncology (ReDO)—chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 2017, 11, 781.
[41]
(a)Kužnik, A.; Benčina, M.; Švajger, U.; Jeras, M.; Rozman, B.; Jerala, R. Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J. Immunol., 2011, 186(8), 4794-4804.
[http://dx.doi.org/10.4049/jimmunol.1000702] [PMID: 21398612]
(b)Zhang, Y.; Wang, Q.; Ma, A.; Li, Y.; Li, R.; Wang, Y. Functional expression of TLR9 in esophageal cancer. Oncol. Rep., 2014, 31(5), 2298-2304.
[http://dx.doi.org/10.3892/or.2014.3095] [PMID: 24647486]
[42]
Kim, E.L.; Wüstenberg, R.; Rübsam, A.; Schmitz-Salue, C.; Warnecke, G.; Bücker, E-M.; Pettkus, N.; Speidel, D.; Rohde, V.; Schulz-Schaeffer, W.; Deppert, W.; Giese, A. Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells. Neuro-oncol., 2010, 12(4), 389-400.
[http://dx.doi.org/10.1093/neuonc/nop046] [PMID: 20308316]
[43]
(a)Tojo, A.; Hatakeyama, S.; Nangaku, M.; Ishimitsu, T. H +-ATPase blockade reduced renal gluconeogenesis and plasma glucose in a diabetic rat model. Med. Mol. Morphol., 2018, 51(2), 89-95..
[http://dx.doi.org/10.1007/s00795-017-0175-6] [PMID: 29318388]
(b)Jin, L.; Alesi, G.N.; Kang, S. Glutaminolysis as a target for cancer therapy. Oncogene, 2016, 35(28), 3619-3625.
[http://dx.doi.org/10.1038/onc.2015.447] [PMID: 26592449]
[44]
Vinod Prabhu, V.; Elangovan, P.; Niranjali Devaraj, S.; Sakthivel, K.M. Targeting apoptosis by 1,2-diazole through regulation of EGFR, Bcl-2 and CDK-2 mediated signaling pathway in human non-small cell lung carcinoma A549 cells. Gene, 2018, 679, 352-359.
[http://dx.doi.org/10.1016/j.gene.2018.09.014] [PMID: 30218747]
[45]
Shi, L.; Middleton, J.; Jeon, Y-J.; Magee, P.; Veneziano, D.; Laganà, A.; Leong, H.S.; Sahoo, S.; Fassan, M.; Booton, R.; Shah, R.; Crosbie, P.A.J.; Garofalo, M. KRAS induces lung tumorigenesis through microRNAs modulation. Cell Death Dis., 2018, 9(2), 219.
[http://dx.doi.org/10.1038/s41419-017-0243-9] [PMID: 29440633]
[46]
Román, M.; Baraibar, I.; López, I.; Nadal, E.; Rolfo, C.; Vicent, S.; Gil-Bazo, I. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Mol. Cancer, 2018, 17(1), 33.
[http://dx.doi.org/10.1186/s12943-018-0789-x] [PMID: 29455666]
[47]
Mortenson, M.M.; Schlieman, M.G.; Virudachalam, S.; Bold, R.J. Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line. Cancer Chemother. Pharmacol., 2004, 54(4), 343-353.
[http://dx.doi.org/10.1007/s00280-004-0811-4] [PMID: 15197486]
[48]
Wei, J.; Zhao, J.; Long, M.; Han, Y.; Wang, X.; Lin, F.; Ren, J.; He, T.; Zhang, H. p21WAF1/CIP1 gene transcriptional activation exerts cell growth inhibition and enhances chemosensitivity to cisplatin in lung carcinoma cell. BMC Cancer, 2010, 10(1), 632.
[http://dx.doi.org/10.1186/1471-2407-10-632] [PMID: 21087528]
[49]
Wolfram, J.; Nizzero, S.; Liu, H.; Li, F.; Zhang, G.; Li, Z.; Shen, H.; Blanco, E.; Ferrari, M. A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery. Sci. Rep., 2017, 7(1), 13738.
[http://dx.doi.org/10.1038/s41598-017-14221-2] [PMID: 29062065]

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