第一型自體顯性多囊基因（轉譯出第一型自體顯性多囊蛋白，簡稱PC1）的突變是造成自體顯性多囊疾病（ADPKD）的主要原因。然而，目前在微小核醣核酸對於第一型自體顯性多囊基因的調控以及如何透過胰島素樣生長因子接受器活化下游的訊息路徑造成第一型自體顯性多囊疾病仍然是不清楚的。因此我們利用多種生物資訊軟體預測在第一型自體顯性多囊疾病鼠及人類的腎臟中，存有會調控第一型自體顯性多囊基因的微小核醣核酸。在螢光原位雜交及反轉錄-聚合酶連鎖反應的實驗中，微小核醣核酸-200c在第一型自體顯性多囊疾病鼠及人類的腎臟中呈現有意義高度的表達。反之，第一型自體顯性多囊蛋白則呈現低表現的情形，這表示兩者存在著高度的相關性。在體外實驗中，冷光報導基因分析證實了微小核醣核酸-200c會標靶在第一型自體顯性多囊基因的三端非轉譯的區域，以及會活化第一型類胰島素生長因子接受器及下游的訊息路徑造成細胞增生和囊泡的形成。此外，在第一型自體顯性多囊疾病鼠中的微小核醣核酸-200c、第一型類胰島素生長因子接受器及胰島素接受器也呈現年紀的增長而有顯著增加情形。以上的結果證實在第一型自體顯性多囊疾病中，微小核醣核酸-200c的高度表達會抑制第一型自體顯性多囊基因的表現，以及活化第一型類胰島素生長因子接受器及胰島素接受器。基於以上的發現，我們進一步探討抑制微小核醣核酸-200c為策略在ADPKD中治療的可能性。吾人認為「在第一型自體顯性多囊疾病中，腎臟專一性標靶磁性氧化鐵奈米粒子所包覆的抗微小核醣核酸-200c可能得以抑制細胞增生和囊泡的形成」。所以我們利磁性氧化鐵奈米粒子包覆抗微小核醣核酸-200c和羅丹明6G細胞染劑的奈米粒子(NO AKSP NP)，並且磁性氧化鐵奈米粒子表面連接抗腎臟專一性蛋白(AKSP NP)。因此，此奈米粒子具有同時包覆多個抗微小核醣核酸200c與專一性標靶到組織上的特性，避免抗微小核醣核酸200c在體內被降解並且能專一性維持抗微小核醣核酸200c在腎臟組織中藥物濃度，並且可避免對其他組織或器官可能造成不良的副作用。我們首先在於體外細胞實驗中證實了這兩種奈米粒子的生物安全性與穩定性。在標靶的實驗中腎臟標靶磁性氧化鐵奈米粒子具有與腎臟細胞較高的結合力，並驗證了第一型自體顯性多囊細胞模式專一性標靶結合的可行性。此外我們也運用核磁共振攝影證明了腎臟專一性標靶磁性氧化鐵奈米粒子標靶腎臟的效果。最後在三维多囊腎細胞培養模式中，包覆著磁性氧化鐵奈米粒子中的微小核醣核酸200c對於細胞增生和囊泡形成有顯著的抑制效果。總和以上結果，吾人將對未來有關第一型自體多囊腎疾病的治療提供了以磁性氧化鐵奈米粒子包覆抗微小核醣核酸200c並於表面連接抗腎臟專一性蛋白為策略的創新治療方法。

Mutations in PKD1, which encodes polycystin-1 (PC1), are a major cause of autosomal dominant polycystic kidney disease (ADPKD). The role of microRNAs (miRNAs) in modulating PKD1 dosage and in inducing IGF-1R/INS-R/PI3K/AKT and MAPK pathways in ADPKD is unclear. We used cross-validation procedures, predicted candidate miRNAs by using bioinformatics tools, and assessed the roles of these predicted miRNAs in modulating PKD1 expression in the kidneys of Pkd1L3/L3 mice and patients with ADPKD. We observed a significant correlation between miRNA-200c overexpression with PC1 low expression in Pkd1L3/L3 mice and patients with ADPKD by the FISH and RT-qPCR experiment. Moreover, we confirmed that miRNA-200c directly targeted the Pkd1 3’-untranslated region (UTR) and thereby promoted cell proliferation and cyst formation through the IGF-1R/INS-R/PI3K/AKT and MAPK pathways in vitro. Pretreatment with IGF-1R, PI3K, and ERK inhibitors significantly inhibited the IGF-1R/INS-R/PI3K/AKT and MAPK pathways in and thus the proliferation of and cyst formation by miRNA-200c-overexpressing cells, which showed low PC1 expression. Furthermore, we found that miRNA-200c, IGF-1R, and INS-R expression increased with age and was correlated with disease severity in Pkd1L3/L3 mice. Based on these findings and the therapeutic role of miRNA-200c in ADPKD, we hypothesized that kidney-specific systemic anti-miRNA-200c treatment could inhibit the proliferation of and cyst formation by the cellular model of ADPKD. For this, we synthesized magnetic nanoparticles (MNPs) as drug carriers containing rhodamine 6G dye (R6G; a cell-tracking marker) and anti-miRNA200c and ligated these MNPs with or without anti-kidney-specific protein (AKSP and NO AKSP NPs, respectively). The use of this nanocarrier system prevented anti-miRNA-200c degradation in the blood, induced low side effects, and maintained high local concentration of anti-miRNA-200c in kidney cells. AKSP NPs and NO AKSP NPs were found to be safe and stable both in vitro and in vivo. We also found that AKSP NPs showed high targeting efficiency and increased binding ability toward the cellular model of ADPKD. Results of MRI showed that AKSP NPs showed higher targeting efficiency than NO AKSP NPs in vivo. Finally, we found that anti-miRNA-200c of AKSP NP and NO AKSP NP has a significant inhibitory effect on cell proliferation and cyst formation in ADPKD cellular model. Thus, this extensive study provides a novel approach of using anti-miRNA-200c encapsulated in AKSP-conjugated MNPs to inhibit miRNA-200c function for treating ADPKD.

1. Jiang ST, Chiou YY, Wang E, Lin HK, Lin YT, Chi YC, Wang CK, Tang MJ, Li H: Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am J Pathol 2006, 168:205-220.
2. Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, Rossetti S, Torres VE, Harris PC: Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest 2012, 122:4257-4273.
3. Wang E, Hsieh-Li HM, Chiou YY, Chien YL, Ho HH, Chin HJ, Wang CK, Liang SC, Jiang ST: Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1. J Pathol 2010, 222:238-248.
4. Dweep H, Sticht C, Kharkar A, Pandey P, Gretz N: Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: using PKD/Mhm rat model. PLoS One 2013, 8:e53780.
5. Pandey P, Brors B, Srivastava PK, Bott A, Boehn SN, Groene HJ, Gretz N: Microarray-based approach identifies microRNAs and their target functional patterns in polycystic kidney disease. BMC Genomics 2008, 9:624.
6. Pandey P, Qin S, Ho J, Zhou J, Kreidberg JA: Systems biology approach to identify transcriptome reprogramming and candidate microRNA targets during the progression of polycystic kidney disease. BMC Syst Biol 2011, 5:56.
7. Grantham JJ: The etiology, pathogenesis, and treatment of autosomal dominant polycystic kidney disease: recent advances. Am J Kidney Dis 1996, 28:788-803.
8. Torres VE, Harris PC: Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009, 76:149-168.
9. Chapin HC, Caplan MJ: The cell biology of polycystic kidney disease. J Cell Biol 2010, 191:701-710.
10. Leuenroth SJ, Crews CM: Targeting cyst initiation in ADPKD. J Am Soc Nephrol 2009, 20:1-3.
11. Tahvanainen E, Tahvanainen P, Kaariainen H, Hockerstedt K: Polycystic liver and kidney diseases. Ann Med 2005, 37:546-555.
12. Grantham JJ, Torres VE, Chapman AB, Guay-Woodford LM, Bae KT, King BF, Jr., Wetzel LH, Baumgarten DA, Kenney PJ, Harris PC, et al: Volume progression in polycystic kidney disease. N Engl J Med 2006, 354:2122-2130.
13. Guay-Woodford LM, Galliani CA, Musulman-Mroczek E, Spear GS, Guillot AP, Bernstein J: Diffuse renal cystic disease in children: morphologic and genetic correlations. Pediatr Nephrol 1998, 12:173-182.
14. Kaariainen H, Koskimies O, Norio R: Dominant and recessive polycystic kidney disease in children: evaluation of clinical features and laboratory data. Pediatr Nephrol 1988, 2:296-302.
15. Ong AC, Devuyst O, Knebelmann B, Walz G: Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet 2015, 385:1993-2002.
16. Boucher C, Sandford R: Autosomal dominant polycystic kidney disease (ADPKD, MIM 173900, PKD1 and PKD2 genes, protein products known as polycystin-1 and polycystin-2). Eur J Hum Genet 2004, 12:347-354.
17. Harris PC, Rossetti S: Molecular diagnostics for autosomal dominant polycystic kidney disease. Nat Rev Nephrol 2010, 6:197-206.
18. Polycystic kidney disease: the complete structure of the PKD1 gene and its protein. The International Polycystic Kidney Disease Consortium. Cell 1995, 81:289-298.
19. Wilson PD: Polycystic kidney disease. N Engl J Med 2004, 350:151-164.
20. Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, et al: PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 1996, 272:1339-1342.
21. Koulen P, Cai Y, Geng L, Maeda Y, Nishimura S, Witzgall R, Ehrlich BE, Somlo S: Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol 2002, 4:191-197.
22. Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, Sukhatme VP, Guggino WB, Germino GG: Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature 2000, 408:990-994.
23. Rossetti S, Burton S, Strmecki L, Pond GR, San Millan JL, Zerres K, Barratt TM, Ozen S, Torres VE, Bergstralh EJ, et al: The position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease. J Am Soc Nephrol 2002, 13:1230-1237.
24. Hateboer N, v Dijk MA, Bogdanova N, Coto E, Saggar-Malik AK, San Millan JL, Torra R, Breuning M, Ravine D: Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group. Lancet 1999, 353:103-107.
25. Audrezet MP, Cornec-Le Gall E, Chen JM, Redon S, Quere I, Creff J, Benech C, Maestri S, Le Meur Y, Ferec C: Autosomal dominant polycystic kidney disease: comprehensive mutation analysis of PKD1 and PKD2 in 700 unrelated patients. Hum Mutat 2012, 33:1239-1250.
26. Rossetti S, Consugar MB, Chapman AB, Torres VE, Guay-Woodford LM, Grantham JJ, Bennett WM, Meyers CM, Walker DL, Bae K, et al: Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2007, 18:2143-2160.
27. Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
28. Esquela-Kerscher A, Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer 2006, 6:259-269.
29. Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, et al: Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 2000, 408:86-89.
30. Cao Y, Semanchik N, Lee SH, Somlo S, Barbano PE, Coifman R, Sun Z: Chemical modifier screen identifies HDAC inhibitors as suppressors of PKD models. Proc Natl Acad Sci U S A 2009, 106:21819-21824.
31. Pastorelli LM, Wells S, Fray M, Smith A, Hough T, Harfe BD, McManus MT, Smith L, Woolf AS, Cheeseman M, Greenfield A: Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome 2009, 20:140-151.
32. Patel V, Hajarnis S, Williams D, Hunter R, Huynh D, Igarashi P: MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol 2012, 23:1941-1948.
33. Park EY, Woo YM, Park JH: Polycystic kidney disease and therapeutic approaches. BMB Rep 2011, 44:359-368.
34. Tan YC, Blumenfeld J, Rennert H: Autosomal dominant polycystic kidney disease: genetics, mutations and microRNAs. Biochim Biophys Acta 2011, 1812:1202-1212.
35. Sun H, Li QW, Lv XY, Ai JZ, Yang QT, Duan JJ, Bian GH, Xiao Y, Wang YD, Zhang Z, et al: MicroRNA-17 post-transcriptionally regulates polycystic kidney disease-2 gene and promotes cell proliferation. Mol Biol Rep 2010, 37:2951-2958.
36. Tran U, Zakin L, Schweickert A, Agrawal R, Doger R, Blum M, De Robertis EM, Wessely O: The RNA-binding protein bicaudal C regulates polycystin 2 in the kidney by antagonizing miR-17 activity. Development 2010, 137:1107-1116.
37. Patel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P: miR-17~92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proc Natl Acad Sci U S A 2013, 110:10765-10770.
38. Attanasio M, Uhlenhaut NH, Sousa VH, O'Toole JF, Otto E, Anlag K, Klugmann C, Treier AC, Helou J, Sayer JA, et al: Loss of GLIS2 causes nephronophthisis in humans and mice by increased apoptosis and fibrosis. Nat Genet 2007, 39:1018-1024.
39. Gretz N, Kranzlin B, Pey R, Schieren G, Bach J, Obermuller N, Ceccherini I, Kloting I, Rohmeiss P, Bachmann S, Hafner M: Rat models of autosomal dominant polycystic kidney disease. Nephrol Dial Transplant 1996, 11 Suppl 6:46-51.
40. Dweep H, Sticht C, Pandey P, Gretz N: miRWalk--database: prediction of possible miRNA binding sites by "walking" the genes of three genomes. J Biomed Inform 2011, 44:839-847.
41. Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, Ratcliffe PJ, Gattner K, Harris PC: Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci U S A 1996, 93:1524-1528.
42. Thivierge C, Kurbegovic A, Couillard M, Guillaume R, Cote O, Trudel M: Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol 2006, 26:1538-1548.
43. Burtey S, Riera M, Ribe E, Pennekamp P, Passage E, Rance R, Dworniczak B, Fontes M: Overexpression of PKD2 in the mouse is associated with renal tubulopathy. Nephrol Dial Transplant 2008, 23:1157-1165.
44. Vujic M, Heyer CM, Ars E, Hopp K, Markoff A, Orndal C, Rudenhed B, Nasr SH, Torres VE, Torra R, et al: Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD. J Am Soc Nephrol 2010, 21:1097-1102.
45. Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, Verbeek S, Deruiter MC, Breuning MH, de Heer E, Peters DJ: Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet 2004, 13:3069-3077.
46. Rossetti S, Kubly VJ, Consugar MB, Hopp K, Roy S, Horsley SW, Chauveau D, Rees L, Barratt TM, van't Hoff WG, et al: Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int 2009, 75:848-855.
47. Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008, 8:915-928.
48. Moschos SJ, Mantzoros CS: The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology 2002, 63:317-332.
49. Song X, Di Giovanni V, He N, Wang K, Ingram A, Rosenblum ND, Pei Y: Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks. Hum Mol Genet 2009, 18:2328-2343.
50. Parker E, Newby LJ, Sharpe CC, Rossetti S, Streets AJ, Harris PC, O'Hare MJ, Ong AC: Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int 2007, 72:157-165.
51. Liu C, Zhang Y, Yuan L, Fu L, Mei C: Rosiglitazone inhibits insulin-like growth factor1-induced polycystic kidney disease cell growth and p70S6 kinase activation. Mol Med Rep 2013, 8:861-864.
52. Nakamura T, Ebihara I, Nagaoka I, Tomino Y, Nagao S, Takahashi H, Koide H: Growth factor gene expression in kidney of murine polycystic kidney disease. J Am Soc Nephrol 1993, 3:1378-1386.
53. Aukema HM, Housini I: Dietary soy protein effects on disease and IGF-I in male and female Han:SPRD-cy rats. Kidney Int 2001, 59:52-61.
54. Mehls O, Irzynjec T, Ritz E, Eden S, Kovacs G, Klaus G, Floege J, Mall G: Effects of rhGH and rhIGF-1 on renal growth and morphology. Kidney Int 1993, 44:1251-1258.
55. Du J, Wilson PD: Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol 1995, 269:C487-495.
56. Matsell DG, Bennett T, Armstrong RA, Goodyer P, Goodyer C, Han VK: Insulin-like growth factor (IGF) and IGF binding protein gene expression in multicystic renal dysplasia. J Am Soc Nephrol 1997, 8:85-94.
57. Bach LA, Hale LJ: Insulin-like growth factors and kidney disease. Am J Kidney Dis 2015, 65:327-336.
58. Oh Y: The insulin-like growth factor system in chronic kidney disease: Pathophysiology and therapeutic opportunities. Kidney Res Clin Pract 2012, 31:26-37.
59. Wang V, Wu W: MicroRNA-based therapeutics for cancer. BioDrugs 2009, 23:15-23.
60. Wichadakul D, Mhuantong W, Jongkaewwattana A, Ingsriswang S: A computational tool for the design of live attenuated virus vaccine based on microRNA-mediated gene silencing. BMC Genomics 2012, 13 Suppl 7:S15.
61. Hansen TF, Christensen R, Andersen RF, Sorensen FB, Johnsson A, Jakobsen A: MicroRNA-126 and epidermal growth factor-like domain 7-an angiogenic couple of importance in metastatic colorectal cancer. Results from the Nordic ACT trial. Br J Cancer 2013, 109:1243-1251.
62. Liu Y, Zhou Y, Feng X, An P, Quan X, Wang H, Ye S, Yu C, He Y, Luo H: MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways. Int J Oncol 2014, 44:203-210.
63. Wu M, Meng Q, Chen Y, Du Y, Zhang L, Li Y, Zhang L, Shi J: Large-pore ultrasmall mesoporous organosilica nanoparticles: micelle/precursor co-templating assembly and nuclear-targeted gene delivery. Adv Mater 2015, 27:215-222.
64. Kotterman MA, Chalberg TW, Schaffer DV: Viral Vectors for Gene Therapy: Translational and Clinical Outlook. Annu Rev Biomed Eng 2015, 17:63-89.
65. Boulaiz H, Marchal JA, Prados J, Melguizo C, Aranega A: Non-viral and viral vectors for gene therapy. Cell Mol Biol (Noisy-le-grand) 2005, 51:3-22.
66. Pang Y, Wang C, Wang J, Sun Z, Xiao R, Wang S: Fe(3)O(4)@Ag magnetic nanoparticles for microRNA capture and duplex-specific nuclease signal amplification based SERS detection in cancer cells. Biosens Bioelectron 2016, 79:574-580.
67. Yin PT, Shah BP, Lee KB: Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells. Small 2014, 10:4106-4112.
68. Rapti K, Chaanine AH, Hajjar RJ: Targeted gene therapy for the treatment of heart failure. Can J Cardiol 2011, 27:265-283.
69. Pouton CW, Seymour LW: Key issues in non-viral gene delivery. Adv Drug Deliv Rev 2001, 46:187-203.
70. Robbins PD, Ghivizzani SC: Viral vectors for gene therapy. Pharmacol Ther 1998, 80:35-47.
71. McNamara JO, 2nd, Andrechek ER, Wang Y, Viles KD, Rempel RE, Gilboa E, Sullenger BA, Giangrande PH: Cell type-specific delivery of siRNAs with aptamer-siRNA chimeras. Nat Biotechnol 2006, 24:1005-1015.
72. Hayashi Y, Yamauchi J, Khalil IA, Kajimoto K, Akita H, Harashima H: Cell penetrating peptide-mediated systemic siRNA delivery to the liver. Int J Pharm 2011, 419:308-313.
73. Song E, Zhu P, Lee SK, Chowdhury D, Kussman S, Dykxhoorn DM, Feng Y, Palliser D, Weiner DB, Shankar P, et al: Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nat Biotechnol 2005, 23:709-717.
74. Kortylewski M, Swiderski P, Herrmann A, Wang L, Kowolik C, Kujawski M, Lee H, Scuto A, Liu Y, Yang C, et al: In vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responses. Nat Biotechnol 2009, 27:925-932.
75. Shu D, Li H, Shu Y, Xiong G, Carson WE, 3rd, Haque F, Xu R, Guo P: Systemic Delivery of Anti-miRNA for Suppression of Triple Negative Breast Cancer Utilizing RNA Nanotechnology. ACS Nano 2015, 9:9731-9740.
76. Kheirolomoom A, Kim CW, Seo JW, Kumar S, Son DJ, Gagnon MK, Ingham ES, Ferrara KW, Jo H: Multifunctional Nanoparticles Facilitate Molecular Targeting and miRNA Delivery to Inhibit Atherosclerosis in ApoE(-/-) Mice. ACS Nano 2015, 9:8885-8897.
77. Campani V, De Rosa G, Misso G, Zarone MR, Grimaldi A: Lipid Nanoparticles to Deliver miRNA in Cancer. Curr Pharm Biotechnol 2016, 17:741-749.
78. Ananta JS, Paulmurugan R, Massoud TF: Nanoparticle-Delivered Antisense MicroRNA-21 Enhances the Effects of Temozolomide on Glioblastoma Cells. Mol Pharm 2015, 12:4509-4517.
79. Liu J, Meng T, Yuan M, Wen L, Cheng B, Liu N, Huang X, Hong Y, Yuan H, Hu F: MicroRNA-200c delivered by solid lipid nanoparticles enhances the effect of paclitaxel on breast cancer stem cell. Int J Nanomedicine 2016, 11:6713-6725.
80. Kim JH, Yeom JH, Ko JJ, Han MS, Lee K, Na SY, Bae J: Effective delivery of anti-miRNA DNA oligonucleotides by functionalized gold nanoparticles. J Biotechnol 2011, 155:287-292.
81. Kim JK, Choi KJ, Lee M, Jo MH, Kim S: Molecular imaging of a cancer-targeting theragnostics probe using a nucleolin aptamer- and microRNA-221 molecular beacon-conjugated nanoparticle. Biomaterials 2012, 33:207-217.
82. Hasebroock KM, Serkova NJ: Toxicity of MRI and CT contrast agents. Expert Opin Drug Metab Toxicol 2009, 5:403-416.
83. Revia RA, Zhang M: Magnetite nanoparticles for cancer diagnosis, treatment, and treatment monitoring: recent advances. Mater Today (Kidlington) 2016, 19:157-168.
84. Tangri N, Hougen I, Alam A, Perrone R, McFarlane P, Pei Y: Total Kidney Volume as a Biomarker of Disease Progression in Autosomal Dominant Polycystic Kidney Disease. Can J Kidney Health Dis 2017, 4:2054358117693355.
85. Bartram MP, Hohne M, Dafinger C, Volker LA, Albersmeyer M, Heiss J, Gobel H, Bronneke H, Burst V, Liebau MC, et al: Conditional loss of kidney microRNAs results in congenital anomalies of the kidney and urinary tract (CAKUT). J Mol Med (Berl) 2013, 91:739-748.
86. Peterson SM, Thompson JA, Ufkin ML, Sathyanarayana P, Liaw L, Congdon CB: Common features of microRNA target prediction tools. Front Genet 2014, 5:23.
87. Han CL, Chien CW, Chen WC, Chen YR, Wu CP, Li H, Chen YJ: A multiplexed quantitative strategy for membrane proteomics: opportunities for mining therapeutic targets for autosomal dominant polycystic kidney disease. Mol Cell Proteomics 2008, 7:1983-1997.
88. Hartig SM: Basic image analysis and manipulation in ImageJ. Curr Protoc Mol Biol 2013, Chapter 14:Unit14.15.
89. Gabow PA: Autosomal dominant polycystic kidney disease. N Engl J Med 1993, 329:332-342.
90. Bao Q, Hughes RC: Galectin-3 expression and effects on cyst enlargement and tubulogenesis in kidney epithelial MDCK cells cultured in three-dimensional matrices in vitro. J Cell Sci 1995, 108 ( Pt 8):2791-2800.
91. Liu B, Li C, Liu Z, Dai Z, Tao Y: Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease. BMC Nephrol 2012, 13:109.
92. Chacon-Heszele MF, Zuo X, Hellman NE, McKenna S, Choi SY, Huang L, Tobias JW, Park KM, Lipschutz JH: Novel MAPK-dependent and -independent tubulogenes identified via microarray analysis of 3D-cultured Madin-Darby canine kidney cells. Am J Physiol Renal Physiol 2014, 306:F1047-1058.
93. Wells EK, Yarborough O, 3rd, Lifton RP, Cantley LG, Caplan MJ: Epithelial morphogenesis of MDCK cells in three-dimensional collagen culture is modulated by interleukin-8. Am J Physiol Cell Physiol 2013, 304:C966-975.
94. Norman J: Fibrosis and progression of autosomal dominant polycystic kidney disease (ADPKD). Biochim Biophys Acta 2011, 1812:1327-1336.
95. Alvaro D, Onori P, Alpini G, Franchitto A, Jefferson DM, Torrice A, Cardinale V, Stefanelli F, Mancino MG, Strazzabosco M, et al: Morphological and functional features of hepatic cyst epithelium in autosomal dominant polycystic kidney disease. Am J Pathol 2008, 172:321-332.
96. Qian F, Watnick TJ, Onuchic LF, Germino GG: The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 1996, 87:979-987.
97. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, Larson C, Brent G, Zhou J: Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet 1997, 17:179-181.
98. Pei Y, Paterson AD, Wang KR, He N, Hefferton D, Watnick T, Germino GG, Parfrey P, Somlo S, St George-Hyslop P: Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease. Am J Hum Genet 2001, 68:355-363.
99. Lu W, Shen X, Pavlova A, Lakkis M, Ward CJ, Pritchard L, Harris PC, Genest DR, Perez-Atayde AR, Zhou J: Comparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects. Hum Mol Genet 2001, 10:2385-2396.
100. Takakura A, Contrino L, Beck AW, Zhou J: Pkd1 inactivation induced in adulthood produces focal cystic disease. J Am Soc Nephrol 2008, 19:2351-2363.
101. Ahrabi AK, Terryn S, Valenti G, Caron N, Serradeil-Le Gal C, Raufaste D, Nielsen S, Horie S, Verbavatz JM, Devuyst O: PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol 2007, 18:1740-1753.
102. Brasier JL, Henske EP: Loss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis. J Clin Invest 1997, 99:194-199.
103. Geng L, Segal Y, Pavlova A, Barros EJ, Lohning C, Lu W, Nigam SK, Frischauf AM, Reeders ST, Zhou J: Distribution and developmentally regulated expression of murine polycystin. Am J Physiol 1997, 272:F451-459.
104. Pritchard L, Sloane-Stanley JA, Sharpe JA, Aspinwall R, Lu W, Buckle V, Strmecki L, Walker D, Ward CJ, Alpers CE, et al: A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype. Hum Mol Genet 2000, 9:2617-2627.
105. Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ: Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 2007, 16:3188-3196.
106. Shibazaki S, Yu Z, Nishio S, Tian X, Thomson RB, Mitobe M, Louvi A, Velazquez H, Ishibe S, Cantley LG, et al: Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1. Hum Mol Genet 2008, 17:1505-1516.
107. Kurbegovic A, Trudel M: Progressive development of polycystic kidney disease in the mouse model expressing Pkd1 extracellular domain. Hum Mol Genet 2013, 22:2361-2375.
108. Kruger J, Rehmsmeier M: RNAhybrid: microRNA target prediction easy, fast and flexible. Nucleic Acids Res 2006, 34:W451-454.
109. Serpico D, Molino L, Di Cosimo S: microRNAs in breast cancer development and treatment. Cancer Treat Rev 2014, 40:595-604.
110. Song C, Liu LZ, Pei XQ, Liu X, Yang L, Ye F, Xie X, Chen J, Tang H, Xie X: miR-200c inhibits breast cancer proliferation by targeting KRAS. Oncotarget 2015, 6:34968-34978.
111. Alvaro D, Metalli VD, Alpini G, Onori P, Franchitto A, Barbaro B, Glaser SS, Francis H, Cantafora A, Blotta I, et al: The intrahepatic biliary epithelium is a target of the growth hormone/insulin-like growth factor 1 axis. J Hepatol 2005, 43:875-883.
112. Leonhard WN, Zandbergen M, Veraar K, van den Berg S, van der Weerd L, Breuning M, de Heer E, Peters DJ: Scattered Deletion of PKD1 in Kidneys Causes a Cystic Snowball Effect and Recapitulates Polycystic Kidney Disease. J Am Soc Nephrol 2015, 26:1322-1333.
113. Tyagi N, Arora S, Deshmukh SK, Singh S, Marimuthu S, Singh AP: Exploiting Nanotechnology for the Development of MicroRNA-Based Cancer Therapeutics. J Biomed Nanotechnol 2016, 12:28-42.
114. Shen J, Attar M: Antibody-Drug Conjugate (ADC) Research in Ophthalmology--a Review. Pharm Res 2015, 32:3572-3576.
115. Parakh S, Parslow AC, Gan HK, Scott AM: Antibody-mediated delivery of therapeutics for cancer therapy. Expert Opin Drug Deliv 2016, 13:401-419.
116. McBain SC, Yiu HH, Dobson J: Magnetic nanoparticles for gene and drug delivery. Int J Nanomedicine 2008, 3:169-180.
117. Yiu HH, McBain SC, Lethbridge ZA, Lees MR, Dobson J: Preparation and characterization of polyethylenimine-coated Fe3O4-MCM-48 nanocomposite particles as a novel agent for magnet-assisted transfection. J Biomed Mater Res A 2010, 92:386-392.
118. Veiseh O, Sun C, Fang C, Bhattarai N, Gunn J, Kievit F, Du K, Pullar B, Lee D, Ellenbogen RG, et al: Specific targeting of brain tumors with an optical/magnetic resonance imaging nanoprobe across the blood-brain barrier. Cancer Res 2009, 69:6200-6207.
119. Hyeon T: Chemical synthesis of magnetic nanoparticles. Chem Commun (Camb) 2003:927-934.
120. Huang C, Zhou Y, Tang Z, Guo X, Qian Z, Zhou S: Synthesis of multifunctional Fe3O4 core/hydroxyapatite shell nanocomposites by biomineralization. Dalton Trans 2011, 40:5026-5031.
121. Barile L, Vassalli G: Exosomes: Therapy delivery tools and biomarkers of diseases. Pharmacol Ther 2017.
122. Huse JT, Holland EC: Targeting brain cancer: advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer 2010, 10:319-331.
123. Park HH, Lee KY, Kim SH, Lee YJ, Koh SH: L-DOPA-induced neurotoxicity is reduced by the activation of the PI3K signaling pathway. Toxicology 2009, 265:80-86.
124. Adams BD, Parsons C, Walker L, Zhang WC, Slack FJ: Targeting noncoding RNAs in disease. J Clin Invest 2017, 127:761-771.
125. Desai MP, Labhasetwar V, Walter E, Levy RJ, Amidon GL: The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent. Pharm Res 1997, 14:1568-1573.
126. Marin T, Montoya P, Arnache O, Calderon J: Influence of Surface Treatment on Magnetic Properties of Fe3O4 Nanoparticles Synthesized by Electrochemical Method. J Phys Chem B 2016, 120:6634-6645.
127. He C, Hu Y, Yin L, Tang C, Yin C: Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 2010, 31:3657-3666.
128. Zhang S, Li J, Lykotrafitis G, Bao G, Suresh S: Size-Dependent Endocytosis of Nanoparticles. Adv Mater 2009, 21:419-424.
129. Lu F, Wu SH, Hung Y, Mou CY: Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles. Small 2009, 5:1408-1413.
130. Calatayud MP, Sanz B, Raffa V, Riggio C, Ibarra MR, Goya GF: The effect of surface charge of functionalized Fe3O4 nanoparticles on protein adsorption and cell uptake. Biomaterials 2014, 35:6389-6399.
131. Zhao Y, Sun X, Zhang G, Trewyn BG, Slowing, II, Lin VS: Interaction of mesoporous silica nanoparticles with human red blood cell membranes: size and surface effects. ACS Nano 2011, 5:1366-1375.
132. Ambros V: The functions of animal microRNAs. Nature 2004, 431:350-355.
133. Erson AE, Petty EM: MicroRNAs in development and disease. Clin Genet 2008, 74:296-306.
134. Stefani G, Slack FJ: Small non-coding RNAs in animal development. Nat Rev Mol Cell Biol 2008, 9:219-230.
135. Lee SO, Masyuk T, Splinter P, Banales JM, Masyuk A, Stroope A, Larusso N: MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease. J Clin Invest 2008, 118:3714-3724.
136. Chow TF, Youssef YM, Lianidou E, Romaschin AD, Honey RJ, Stewart R, Pace KT, Yousef GM: Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. Clin Biochem 2010, 43:150-158.
137. Nakada C, Matsuura K, Tsukamoto Y, Tanigawa M, Yoshimoto T, Narimatsu T, Nguyen LT, Hijiya N, Uchida T, Sato F, et al: Genome-wide microRNA expression profiling in renal cell carcinoma: significant down-regulation of miR-141 and miR-200c. J Pathol 2008, 216:418-427.
138. Siu KW, DeSouza LV, Scorilas A, Romaschin AD, Honey RJ, Stewart R, Pace K, Youssef Y, Chow TF, Yousef GM: Differential protein expressions in renal cell carcinoma: new biomarker discovery by mass spectrometry. J Proteome Res 2009, 8:3797-3807.
139. Lorenzen JM, Martino F, Thum T: Detection and transport mechanisms of circulating microRNAs in neurological, cardiac and kidney diseases. Curr Med Chem 2013, 20:3623-3628.
140. Magenta A, Cencioni C, Fasanaro P, Zaccagnini G, Greco S, Sarra-Ferraris G, Antonini A, Martelli F, Capogrossi MC: miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition. Cell Death Differ 2011, 18:1628-1639.
141. Vasa-Nicotera M, Chen H, Tucci P, Yang AL, Saintigny G, Menghini R, Mahe C, Agostini M, Knight RA, Melino G, Federici M: miR-146a is modulated in human endothelial cell with aging. Atherosclerosis 2011, 217:326-330.
142. Andreassen M, Raymond I, Kistorp C, Hildebrandt P, Faber J, Kristensen LO: IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population. Eur J Endocrinol 2009, 160:25-31.
143. Zha J, Lackner MR: Targeting the insulin-like growth factor receptor-1R pathway for cancer therapy. Clin Cancer Res 2010, 16:2512-2517.
144. Zemva J, Schubert M: Central insulin and insulin-like growth factor-1 signaling: implications for diabetes associated dementia. Curr Diabetes Rev 2011, 7:356-366.
145. O'Neill C, Kiely AP, Coakley MF, Manning S, Long-Smith CM: Insulin and IGF-1 signalling: longevity, protein homoeostasis and Alzheimer's disease. Biochem Soc Trans 2012, 40:721-727.
146. Piccirillo R, Demontis F, Perrimon N, Goldberg AL: Mechanisms of muscle growth and atrophy in mammals and Drosophila. Dev Dyn 2014, 243:201-215.
147. Nagao S, Yamaguchi T, Kusaka M, Maser RL, Takahashi H, Cowley BD, Grantham JJ: Renal activation of extracellular signal-regulated kinase in rats with autosomal-dominant polycystic kidney disease. Kidney Int 2003, 63:427-437.
148. Omori S, Hida M, Fujita H, Takahashi H, Tanimura S, Kohno M, Awazu M: Extracellular signal-regulated kinase inhibition slows disease progression in mice with polycystic kidney disease. J Am Soc Nephrol 2006, 17:1604-1614.
149. Yamaguchi T, Nagao S, Wallace DP, Belibi FA, Cowley BD, Pelling JC, Grantham JJ: Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys. Kidney Int 2003, 63:1983-1994.
150. Rivas DA, Lessard SJ, Rice NP, Lustgarten MS, So K, Goodyear LJ, Parnell LD, Fielding RA: Diminished skeletal muscle microRNA expression with aging is associated with attenuated muscle plasticity and inhibition of IGF-1 signaling. Faseb j 2014, 28:4133-4147.
151. Kim K, Drummond I, Ibraghimov-Beskrovnaya O, Klinger K, Arnaout MA: Polycystin 1 is required for the structural integrity of blood vessels. Proc Natl Acad Sci U S A 2000, 97:1731-1736.
152. Boulter C, Mulroy S, Webb S, Fleming S, Brindle K, Sandford R: Cardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene. Proc Natl Acad Sci U S A 2001, 98:12174-12179.
153. Griffin MD, Torres VE, Grande JP, Kumar R: Vascular expression of polycystin. J Am Soc Nephrol 1997, 8:616-626.
154. Qian Q, Li M, Cai Y, Ward CJ, Somlo S, Harris PC, Torres VE: Analysis of the polycystins in aortic vascular smooth muscle cells. J Am Soc Nephrol 2003, 14:2280-2287.
155. Chapman AB, Stepniakowski K, Rahbari-Oskoui F: Hypertension in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 2010, 17:153-163.
156. Hassane S, Claij N, Lantinga-van Leeuwen IS, Van Munsteren JC, Van Lent N, Hanemaaijer R, Breuning MH, Peters DJ, DeRuiter MC: Pathogenic sequence for dissecting aneurysm formation in a hypomorphic polycystic kidney disease 1 mouse model. Arterioscler Thromb Vasc Biol 2007, 27:2177-2183.
157. Ruster C, Wolf G: Angiotensin II as a morphogenic cytokine stimulating renal fibrogenesis. J Am Soc Nephrol 2011, 22:1189-1199.
158. Weigert C, Brodbeck K, Klopfer K, Haring HU, Schleicher ED: Angiotensin II induces human TGF-beta 1 promoter activation: similarity to hyperglycaemia. Diabetologia 2002, 45:890-898.
159. Kato M, Arce L, Wang M, Putta S, Lanting L, Natarajan R: A microRNA circuit mediates transforming growth factor-beta1 autoregulation in renal glomerular mesangial cells. Kidney Int 2011, 80:358-368.
160. Chea SW, Lee KB: TGF-beta mediated epithelial-mesenchymal transition in autosomal dominant polycystic kidney disease. Yonsei Med J 2009, 50:105-111.
161. Hassane S, Leonhard WN, van der Wal A, Hawinkels LJ, Lantinga-van Leeuwen IS, ten Dijke P, Breuning MH, de Heer E, Peters DJ: Elevated TGFbeta-Smad signalling in experimental Pkd1 models and human patients with polycystic kidney disease. J Pathol 2010, 222:21-31.
162. Farokhzad OC, Langer R: Impact of nanotechnology on drug delivery. ACS Nano 2009, 3:16-20.
163. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R: Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007, 2:751-760.
164. Wang AZ, Langer R, Farokhzad OC: Nanoparticle delivery of cancer drugs. Annu Rev Med 2012, 63:185-198.
165. Heath JR, Davis ME: Nanotechnology and cancer. Annu Rev Med 2008, 59:251-265.
166. Davis ME, Chen ZG, Shin DM: Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 2008, 7:771-782.
167. Choi HS, Liu W, Liu F, Nasr K, Misra P, Bawendi MG, Frangioni JV: Design considerations for tumour-targeted nanoparticles. Nat Nanotechnol 2010, 5:42-47.
168. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV: Renal clearance of quantum dots. Nat Biotechnol 2007, 25:1165-1170.
169. Choi CH, Zuckerman JE, Webster P, Davis ME: Targeting kidney mesangium by nanoparticles of defined size. Proc Natl Acad Sci U S A 2011, 108:6656-6661.
170. Kannan RM, Nance E, Kannan S, Tomalia DA: Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med 2014, 276:579-617.
171. Roy U, Rodriguez J, Barber P, das Neves J, Sarmento B, Nair M: The potential of HIV-1 nanotherapeutics: from in vitro studies to clinical trials. Nanomedicine (Lond) 2015, 10:3597-3609.
172. Mignani S, El Kazzouli S, Bousmina M, Majoral JP: Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview. Adv Drug Deliv Rev 2013, 65:1316-1330.
173. Dreaden EC, Mackey MA, Huang X, Kang B, El-Sayed MA: Beating cancer in multiple ways using nanogold. Chem Soc Rev 2011, 40:3391-3404.
174. Anselmo AC, Mitragotri S: A Review of Clinical Translation of Inorganic Nanoparticles. Aaps j 2015, 17:1041-1054.
175. Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA: Gold nanoparticles for biology and medicine. Angew Chem Int Ed Engl 2010, 49:3280-3294.
176. Paithankar D, Hwang BH, Munavalli G, Kauvar A, Lloyd J, Blomgren R, Faupel L, Meyer T, Mitragotri S: Ultrasonic delivery of silica-gold nanoshells for photothermolysis of sebaceous glands in humans: Nanotechnology from the bench to clinic. J Control Release 2015, 206:30-36.
177. Yang Y, Yu C: Advances in silica based nanoparticles for targeted cancer therapy. Nanomedicine 2016, 12:317-332.
178. Meng H, Wang M, Liu H, Liu X, Situ A, Wu B, Ji Z, Chang CH, Nel AE: Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano 2015, 9:3540-3557.
179. Laurent S, Forge D, Port M, Roch A, Robic C, Vander Elst L, Muller RN: Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem Rev 2008, 108:2064-2110.
180. Maier-Hauff K, Ulrich F, Nestler D, Niehoff H, Wust P, Thiesen B, Orawa H, Budach V, Jordan A: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J Neurooncol 2011, 103:317-324.
181. Maggiorella L, Barouch G, Devaux C, Pottier A, Deutsch E, Bourhis J, Borghi E, Levy L: Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol 2012, 8:1167-1181.
182. Field JA, Luna-Velasco A, Boitano SA, Shadman F, Ratner BD, Barnes C, Sierra-Alvarez R: Cytotoxicity and physicochemical properties of hafnium oxide nanoparticles. Chemosphere 2011, 84:1401-1407.
183. Xu X, Ho W, Zhang X, Bertrand N, Farokhzad O: Cancer nanomedicine: from targeted delivery to combination therapy. Trends Mol Med 2015, 21:223-232.
184. Song W, Luo Y, Zhao Y, Liu X, Zhao J, Luo J, Zhang Q, Ran H, Wang Z, Guo D: Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study. Nanomedicine (Lond) 2017.
185. Valencia PM, Pridgen EM, Perea B, Gadde S, Sweeney C, Kantoff PW, Bander NH, Lippard SJ, Langer R, Karnik R, Farokhzad OC: Synergistic cytotoxicity of irinotecan and cisplatin in dual-drug targeted polymeric nanoparticles. Nanomedicine (Lond) 2013, 8:687-698.
186. Kim J, Kim J, Jeong C, Kim WJ: Synergistic nanomedicine by combined gene and photothermal therapy. Adv Drug Deliv Rev 2016, 98:99-112.
187. Yang C, Xiong F, Dou J, Xue J, Zhan X, Shi F, Li M, Wu S, Luo S, Zhang T, et al: Target therapy of multiple myeloma by PTX-NPs and ABCG2 antibody in a mouse xenograft model. Oncotarget 2015, 6:27714-27724.
188. Son A, Dhirapong A, Dosev DK, Kennedy IM, Weiss RH, Hristova KR: Rapid and quantitative DNA analysis of genetic mutations for polycystic kidney disease (PKD) using magnetic/luminescent nanoparticles. Anal Bioanal Chem 2008, 390:1829-1835.
189. Zhou X, Bao H, Takakura A, Zhou J, Albert M, Sun Y: Polycystic kidney disease evaluation by magnetic resonance imaging in ischemia-reperfusion injured PKD1 knockout mouse model: comparison of T2-weighted FSE and true-FISP. Invest Radiol 2010, 45:24-28.
190. Bae KT, Zhu F, Chapman AB, Torres VE, Grantham JJ, Guay-Woodford LM, Baumgarten DA, King BF, Jr., Wetzel LH, Kenney PJ, et al: Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol 2006, 1:64-69.
191. Wischnjow A, Sarko D, Janzer M, Kaufman C, Beijer B, Brings S, Haberkorn U, Larbig G, Kubelbeck A, Mier W: Renal Targeting: Peptide-Based Drug Delivery to Proximal Tubule Cells. Bioconjug Chem 2016, 27:1050-1057.
192. Zou J, Glinsky VV, Landon LA, Matthews L, Deutscher SL: Peptides specific to the galectin-3 carbohydrate recognition domain inhibit metastasis-associated cancer cell adhesion. Carcinogenesis 2005, 26:309-318.
193. Deutscher SL, Figueroa SD, Kumar SR: Tumor targeting and SPECT imaging properties of an (111)In-labeled galectin-3 binding peptide in prostate carcinoma. Nucl Med Biol 2009, 36:137-146.
194. Geng Q, Sun X, Gong T, Zhang ZR: Peptide-drug conjugate linked via a disulfide bond for kidney targeted drug delivery. Bioconjug Chem 2012, 23:1200-1210.
195. Shao X, Johnson JE, Richardson JA, Hiesberger T, Igarashi P: A minimal Ksp-cadherin promoter linked to a green fluorescent protein reporter gene exhibits tissue-specific expression in the developing kidney and genitourinary tract. J Am Soc Nephrol 2002, 13:1824-1836.