Targeted breast cancer nanotherapeutics: Options and opportunities with estrogen receptors

Critical Reviews in Therapeutic Drug Carrier Systems

Volumn 29, Issue 5, 2012, Pages 421-446

  Paliwal, Shivani Rai ^a   Paliwa, Rishi ^b   Agrawa, Govind P ^b   Vyas, Suresh P ^b  

^a GURU GHASIDAS UNIVERSITY   (India)

^b DR H S GOUR UNIVERSITY   (India)

Author keywords

Breast cancer; Endogenous bioligand; Estrogens; Liposome; Tamoxifen; Targeting

Indexed keywords

BESTRABUCIL; CHLORAMBUCIL; CHLORMETHINE; DENDRIMER; DOXORUBICIN; ELLIPTICINE; ESTRADIOL; ESTRIOL; ESTROGEN; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; ESTRONE; GELDANAMYCIN; LIPOSOME; MITOGEN ACTIVATED PROTEIN KINASE; MITOMYCIN C; NANOCARRIER; NANOPARTICLE; NITROSOUREA; ORAL CONTRACEPTIVE AGENT; PACLITAXEL; POLYAMIDOAMINE; PORPHYRIN; TAMOXIFEN;

ARTICLE; BINDING AFFINITY; BREAST CANCER; CANCER CELL; CANCER GENE THERAPY; CANCER RISK; CANCER SIZE; CELL COMMUNICATION; CELL DIFFERENTIATION; CELL PROLIFERATION; CHEMICAL STRUCTURE; CONJUGATION; DNA BINDING; DRUG DELIVERY SYSTEM; DRUG RECEPTOR BINDING; DRUG TARGETING; ESTROGEN BINDING; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; ESTROGEN RESPONSIVE ELEMENT; FAMILY HISTORY; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC DAMAGE; HUMAN; LIGAND BINDING; MENARCHE; NANOENCAPSULATION; NUCLEAR LOCALIZATION SIGNAL; PHOSPHOLIPID BILAYER; PHOTODYNAMIC THERAPY; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; RETICULOENDOTHELIAL SYSTEM; RISK FACTOR; TRANSCRIPTION INITIATION; TUMOR MICROENVIRONMENT;

ANTINEOPLASTIC AGENTS, HORMONAL; BREAST NEOPLASMS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; FEMALE; HUMANS; NANOPARTICLES; RECEPTORS, ESTROGEN;

EID: 84864581398     PISSN: 07434863     EISSN: None     Source Type: Journal    
DOI: 10.1615/CritRevTherDrugCarrierSyst.v29.i5.20     Document Type: Article

References (124)

1. Vyas SP, Sihorkar V. Endogenous carriers and ligands in non-immunogenic site-specific drug delivery. Adv Drug Deliv Rev. 2000;43:101-64.
2. Vyas SP, Singh A, Sihorkar V. Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting. Crit Rev Ther Drug Carr Sys. 2001;18:1-76.
3. Hager GL, Smith CL, Fragoso G, Wolford R, Walker D, Barsony J, Htun H. Intranuclear trafficking and gene targeting by members of the steroid/nuclear receptor super-family. J Steroid Biochem Mol Biol. 1998;65:125-32.
4. Wasan H, Waxman J. In: Cell proliferation cancer. Puszta LL, Lewis CE, Yap E, Eds. Oxford: Oxford University Press; 1996, pp. 260-81.
5. Henderson BE, Ross R, Bernstein L. Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res. 1998;48:246-53.
6. Rai S, Paliwal R, Vaidya B, Gupta PN, Mahor S, Khatri K, Goyal AK, Rawat A, Vyas SP. Estrogen(s) and analogs as a non-immunogenic endogenous ligand in targeted drug/DNA delivery. Curr Med Chem. 2007;14:2095-2109.
7. Goldhirsch A, Colleoni M, Domenighetti G, Gelber RD. Systemic treatments for women with breast cancer: outcome with relation to screening for the disease. Ann Oncol. 2003;14:1212-14.
8. Sillero-Arenas M, Delgado-Rodriguez M, Rodigues-Canteras R, Bueno-Cavanillas A, Galvez-Vargas R. Menopausal hormone replacement therapy and breast cancer: a metaanalysis. Obstet Gynecol. 1992;79:286-94.
9. Kelsey JL. A review of the epidemiology of human breast cancer. Epidemiol Rev. 1979;1:74-109.
10. Preston-Martin S, Pike MC, Ross RK, Jones PA, Henderson BE. Increased cell division as a cause of human cancer. Cancer Res. 1990;50:7415-21.
11. Yang X, Lippman ME. BRCA1 and BRCA2 in breast cancer. Breast Cancer Res Treat. 1999;54:1-10.
12. de Jong MM, Nolte IM, te Meerman te Meerman GJ, van der Graaf WTA, Oosterwijk JC, Kleibeuker JH, Schaapveld M, de Vries EGE. Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. J Med Genet. 2002;39:225-42.
13. Malkin D, Li FP, Strong LC, Fraumeni Jr JF, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990;250:1233-38.
14. Allred DC, Mohsin SK, Fuqua SA. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer. 2001;8:47-61.
15. MacGillivray MH, Morishima A, Conte F, Grumbach M, Smith EP. Pediatric endocrinology update: an overview. The essential roles of estrogens in pubertal growth, epiphyseal fusion and bone turnover: lessons from mutations in the genes for aromatase and the estrogens receptor. Horm Res. 1998;49:2-8.
16. Norman AW, Litwach G. Estrogens and progestins. London: Academic Press; 1987.
17. Nilsson S, Mäkelä S, Treuter E, Tujague M, Thomsen J, Andersson G, Enmark E, Pettersson K, Gustafsson JA. Mechanisms of estrogen action. Physiol Rev. 2001;81:1535-65.
18. Buchanan DL, Setiawan T, Lubahn DB, Taylor JA, Kurita T, Cunha GR, Cooke PS. Tissue compartment-specific estrogen receptor-alpha participation in the mouse uterine epithelial secretory response. Endocrinology. 1999;140:484-491.
19. Delbes G, Levacher C, Duquenne C, Racine C, Pakarinen P, Habert R. Endogenous estrogens inhibit mouse fetal Leydig cell development via estrogen receptor alpha. Endocrinology. 2005;146:2454-61.
20. Daroo BJ, Korasch KS. Estrogen receptors and human disease. J Clin Invest. 2006;116: 561-70.
21. Morale MC, Serra PA, Lepiscopo F, Tirolo C, Caniglia S, Testa N, Gennuso F, Giaquinta G, Desokle MS, Miele E, Marchetti B. Estrogens, neuroinflammation and neuroprotection in Parkinson's disease: glia dictates resistance versus vulnerability to neurodegeneration. Neuroscience. 2006;138:869-78.
22. Jensen EV, Jacobson HI. Basic guides to the mechanism of estrogen action. Recent Prog Horm Res. 1962;18:387-414.
23. Carson-Jurica MA, Schrader W, O'Malley B. Steroid receptor family: structure and functions. Endocr Rev. 1990;11:201-20.
24. Greene GL, Gilna P, Waterfield M, Baker A, Hort Y, Shine J. Sequence and expression of human estrogen receptor complementary DNA. Science. 1986;231:1150-54.
25. Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA. Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci U S A. 1996;93:5925-30.
26. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA. Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab. 1997;82:4258-65.
27. Penot G, Le Péron C, Mérot Y, Grimaud-Fanouillére E, Ferriere F, Boujrad N, Kah O, Saliqaut C, Ducouret B, Métivier R, Flouriot G. The human estrogen receptor-α isoform hERα46 antagonizes the proliferative influence of hERα66 in MCF7 breast cancer cells. Endocrinology. 2005;146:5474-84.
28. Petersen DN, Tkalcevic GT, Koza-Taylor PH, Turi TG, Brown TA. Identification of estrogen receptor beta2, a functional variant of estrogen receptor beta expressed in normal rat tissues. Endocrinology. 1998;139:1082-92.
29. Li X, Huang J, Yi P, Bambara RA, Hilf R, Muyan M. Single-chain estrogen receptors (ERs) reveal that the ERalpha/β heterodimer emulates functions of the ERalpha dimer in genomic estrogen signaling pathways. Mol Cell Biol. 2004;24:7681-94.
30. Hanstein B, Liu H, Yancisin MC, Brown M. Functional analysis of a novel estrogen receptor- beta isoform. Mol Endocrinol. 1999;13:129-37.
31. O'Malley BW, Tsai MJ. Molecular pathways of steroid receptor action. Biol Reprod. 1992;46:163-67.
32. McInerney EM, Weis KE, Sun J, Mosselman S, Katzenellenbogen BS. Transcription activation by the human estrogen receptor subtype beta (ER beta) studied with ER beta and ER alpha receptor chimeras. Endocrinology. 1998;139:4513-22.
33. Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: structure and function. Curr Opin Cell Biol. 1998;10:384-91.
34. Evans RM. The steroid and thyroid hormone receptor superfamily. Science. 1988;240: 889-95.
35. Murdoch FE, Gorski J. The role of ligand in estrogen receptor regulation of gene expression. Mol Cell Endocrinol. 1991;78:C103-8.
36. McKenna NJ, O'Malley BW. An issue of tissues: divining the split personalities of selective estrogen receptor modulators. Nat Med. 2000;6:960-62.
37. Aronica S, Kraus W, Katzenellenbogen B. Estrogen action via the cAMP signaling pathway: stimulation of adenylate cyclase and cAMP-regulated gene transcription. Proc Natl Acad Sci U S A. 1994;91:8517-21.
38. Levin ER. Cellular functions of the plasma membrane estrogen receptor. Trends Endocrinol Metab. 1999;10:374-77.
39. Szego CM, Pietras RJ. Lysosomal functions in cellular activation: propagation of the actions of hormones and other effectors. Int Rev Cytol. 1984;88:1-302.
40. Ramirez VD, Zheng J. Membrane sex-steroid receptors in the brain. Front Neuroendocrinol. 1996;17:402-39.
41. Mendelsohn ME, Karas RH. The protective effects of estrogens on the cardiovascular system. New Engl J Med. 1999;340:1801-11.
42. Pietras RJ, Szego CM. Specific binding sites for oestrogens at the outer surfaces of isolated endometrial cells. Nature. 1977;265:69-72.
43. Watson CS, Gametchu B. Membrane-initiated steroid actions and the proteins that mediate them. Proc Soc Exp Biol Med. 1999;220:9-19.
44. Migliaccio A, Di Domenico M, Castoria G, de Falco A, Bontempo P, Nola E, Auricchio F. Tyrosine kinase/p21ras/MAP-kinase pathway activation by estradiol-receptor complex in MCF-7 cells. EMBO J. 1996;15:1292-1300.
45. Pietras RJ, Szego CM. Surface modifications evoked by estradiol and diethylstilbestrol in isolated endometrial cells: evidence from lectin probes and extracellular release of lysosomal protease. Nature. 1975;253:357-59.
46. Henderson BE, Feigelson HS. Hormonal carcinogenesis. Carcinogenesis. 2000;21;427-33.
47. Tsai M, O'Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annl Rev Biochem. 1994;63:451-86.
48. Yue W, Wang JP, Li Y, Bocchinfuso WP, Korach KS, Devanesan PD, Rogan E, Cavalieri E, Santen RJ. Tamoxifen versus aromatase inhibitors for breast cancer prevention. Clin Cancer Res. 2005;11:925S-930S.
49. Hulka BS, Stark AT. Breast cancer: cause and prevention. Lancet. 1995;346:883-87.
50. Wiesen JF, Young P, Werb Z, Cunha GR. Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development. 1999;126:335-44.
51. Herynk MH, Fuqua SA. Estrogen receptor mutations in human disease. Endocr Rev. 2004;25:869-98.
52. Cai Q, Shu XO, Jin F, Dai Q, Wen W, Cheng JR, Gao TY, Zheng W. Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiol Biomarkers Prev. 2003;12:853-59.
53. Maguire P, Margolin S, Skoglund J, Sun XF, Gustafsson JA, Borresen-Dale AL, Lindblom A. Estrogen receptor beta (ESR2) polymorphisms in familial and sporadic breast cancer. Breast Cancer Res Treat. 2005;94:145-52.
54. Liao L, Kuang SQ, Yuan Y, Gonzalez SM, O'Malley BW, Xu J. Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1. J Steroid Biochem Mol Biol. 2002;83:3-14.
55. Osborne CK. Tamoxifen in the treatment of breast cancer. New Engl J Med. 1998a;339:1609-18.
56. Koren E, Torchilin VP. Drug carriers for vascular drug delivery. IUBMB Life. 2011;63: 586-95.
57. MeGuire WL, Carbone PP, Sears ME. In: Estrogen receptors in human breast cancer. Me- Guire WL, Carbone PP, Voilmer EP, eds. New York: Raven Press; 1975, p. 1.
58. Blickenstaff RT, ed. Antitumor steroids. San Diego, CA: Academic Press; 1992.
59. Jones GB, Warner PM. On the mechanism of quinone formation from the Bergman cyclization: some theoretical insights. J Org Chem. 2001;66:3688-95.
60. Cassino C, Gabano E, Ravera M, Cravotto G, Palmisano G, Vessieres A, Jaouen G, Mundwiler S, Alberto R, Osella D. Platinum (II) and technetium (I) complexes anchored to the ethynylestradiol carrier. A possible way to drug targeting and delivery. Inorg Chim Acta. 2004;357:2157-66.
61. Lam HY, Ng PK, Goldenberg GJ, Wong CM. Estrogen receptor-binding affinity and cytotoxic activity of three new estrogen-nitrosourea conjugates in human breast cancer cell lines in vitro. Cancer Treat Rep. 1987;71:901-6.
62. Lam HY, Goldenberg GJ, Wong CM. Interaction of estrogen-nitrosourea conjugates with the estrogen receptor in rat uterus. Biochem Pharmacol. 1988;37:2625-31.
63. Sibata CH, Colussi VC, Oleinick NL, Kinsella TJ. Photodynamic therapy in oncology. Expert Opin Pharmacother. 2001;6:917-27.
64. Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, Pena-Diaz J, Otterlei M, Slupphaug G, Krokan HE. Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair. 2004;3:1389-1407.
65. Ueda T, Sakai K, Morimoto K, Nakatani S. Therapeutic results in recurrent breast cancer with the use of Bestrabucil (KM2210). Gan To Kagaku Ryoho. 1987;14:3285-89.
66. Ohsawa N, Yamazaki Z, Wagatsuma T, Isurugi K. Bestrabacil: a possible target-oriented anticancer agent. Gan Kagaku Ryoho. 1984;11:2115-24.
67. Kubota T, Abe O, Izuo M, Watanabe H, Enomoto K, Ohsawa N, Kuno K. A phase II multi-institutional study of estra-1,3,5(10)-triene-3,17 beta-diol, 3-benzoate, 174-4-bis(2- chloroethyl)aminophenyl-1- oxobutoxyacetate (KM2210), a novel antitumor agent, for advanced and recurrent breast carcinoma. Anticancer Res. 1993;13:2361-65.
68. Kubota T, Kawamura E, Suzuki T, Yamada T, Toyoda H, Miyagawa T, Kurokawa T. Antitumor activity and pharmacokinetics of estra- 1,3,5(10)-triene-3,17/3-diol, 3-benzoate,17- ((4-(4-(bis(2-chloroethyl)amino)-phenyl)-l-oxobutoxy)acetate) (bestrabucil) in human tumor xenografts serially transplanted into nude mice. Jpn J Clin Oncol. 1986;16:357-64.
69. Gupta A, Saha P, Descoteaux C, Leblanc V, Asselin E, Berube G. Design, synthesis and biological evaluation of estradiol-chlorambucil hybrids as anticancer agents. Bioorg Med Chem Lett. 2010;20:1614-18.
70. Devraj R, Barrett JF, Fernandez JA, Katzenellenbogen JA, Cushman M. Design, synthesis, and biological evaluation of ellipticine-estradiol conjugates. J Med Chem. 1996;39:3367-74.
71. Wittliff JL, Weidner N, Everson RB, Hall TC. Interactions between estrogen receptors and certain steroidal alkylating agents. Cancer Treat Rep. 1978;62:1262-66.
72. Jones GB, Wright J, Plourde G, Purohit AD, Wyatt J, Hynd G, Fouad F. Synthesis and photochemical activity of designed enediynes. J Am Chem Soc. 2000;122:9872-73.
73. Holmes FA, Walters RS, Theriault RL, Buzdar A, Frye DK, Hortobagyi GN, Forman AD, Newton LK, Raber MN. Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst. 1991;83:1797-1805.
74. Kuduk SD, Zheng FF, Sepp-Lorenzino L, Rosen N, Danishefsky SJ. Synthesis and evaluation of geldanamycin-estradiol hybrids. Bioorg Med Chem Lett. 1999;9:1233-38.
75. Oaksmith JM, Ganem B. Synthesis of a COMC-estradiol conjugate for targeted, tissueselective cancer chemotherapy. Tetrahedron Lett. 2009;50:3497-98.
76. Nofal ZM, El-Zahar MI, AbdEl-Karim SS. Novel coumarin derivatives with expected biological activity. Molecules. 2000;5:99-113.
77. Musaa MA, Khan MO, Cooperwood JS. Synthesis and antiproliferative activity of coumarin- estrogen conjugates against breast cancer cell lines. Lett Drug Des Discov. 2009;6:133-38.
78. Torchilin VP. Targeted pharmaceutical nanocarriers for cancer therapy and imaging. AAPS J. 2007;9:E128-E147.
79. Marquez DC, Pietras RJ. Membrane-associated binding sites for estrogen contribute to growth regulation of human breast cancer cells. Oncogene. 2001;20:5420-30.
80. Harrington WR, Kim SH, Funk CC, Madak-Erdogan Z, Schiff R, Katzenellenbogen JA, Katzenellenbogen BS. Estrogen dendrimer conjugates that preferentially activate extranuclear, nongenomic versus genomic pathways of estrogen action. Mol Endocrinol. 2006;203:491-502.
81. Reddy BS, Banerjee R. 17Beta-estradiol-associated stealth-liposomal delivery of anticancer gene to breast cancer cells. Angew Chem Int Ed. 2005;44:6723-27.
82. Bangham AD, Standish MM, Watkins JC. The action of steroids and streptolysin S on the permeability of phospholipid structures to cations. J Mol Biol. 1965;13:253-59.
83. ElBayoumi TA, Torchilin VP. Tumor-targeted nanomedicines: enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancerspecific monoclonal antibody. Clin Cancer Res. 2009;15:1973-80.
84. Osborne CK. Steroid hormone receptors in breast cancer management. Breast Cancer Res Treat. 1998;51:227-38.
85. Somia N, Verma IM. Gene therapy: trials and tribulations. Nat Rev Genet. 2000;1:91-99.
86. Soriano P, Dijkstra J, Legrand A, Spanjer H, Londos-Gagliardi D, Roerdink F, Scherphof G, Nicolau C. Targeted and nontargeted liposomes for in vivo transfer to rat liver cells of a plasmid containing the preproinsulin I gene. Proc Natl Acad Sci U S A. 1983;80: 7128-31.
87. Wang CY, Huang L. pH-sensitive immunoliposomes mediate target-cell-specific delivery and controlled expression of a foreign gene in mouse. Proc Natl Acad Sci USA. 1987;84:7851-55.
88. Dean DA. Import of plasmid DNA into the nucleus is sequence specific. Exp Cell Res. 1997;230:293-302.
89. Baumann CT, Lim CS, Hager GL. Intracellular localization and trafficking of steroid receptors. Cell Biochem Biophys. 1999;31:119-27.
90. Mangelsdorf DJ, Evans RM. The RXR heterodimers and orphan receptors. Cell. 1995;83:841-50.
91. Wiseman JW, Goddard CA, Colledge WH. Steroid hormone enhancement of gene delivery to a human airway epithelial cell line in vitro and mouse airways in vivo. Gene Ther. 2001;8:1562-71.
92. Koster F, Felberbaum R, Finas D, Wunsch K, Schulz C, Diedrich K, Hauser C. Progesterone and estradiol enhance lipid mediated transfection of Sk-Br-3 mammalian cancer cells. Int J Mol Med. 2002;9:617-20.
93. Paliwal SR, Paliwal R, Agrawal GP, Vyas SP. Liposomal nanomedicine for breast cancer therapy. Nanomedicine. 2011;6:1085-1100.
94. Rai S, Paliwal R, Vaidya B, Khatri K, Goyal AK, Gupta PN, Vyas SP. Targeted delivery of doxorubicin via estrone-appended liposomes. J Drug Target. 2008;16:455-63.
95. Paliwal SR, Paliwal R, Mishra N, Mehta A, Vyas SP. A novel cancer targeting approach based on estrone anchored stealth liposome for site-specific breast cancer therapy. Curr Cancer Drug Targets. 2010;10:343-53.
96. Patri AK, Kukowska-Latallo JF, Baker JR. Targeted drug delivery with dendrimers: comparison of the release kinetics of covalently conjugated drug and non-covalent drug inclusion complex. Adv Drug Deliv Rev. 2005;57:2203-14.
97. Wu C, Brechbiel MW, Kozak RW, Gansow OA. Metal-chelate-dendrimer-antibody constructs for use in radioimmunotherapy and imaging. Bioorg Med Chem Lett. 1994;4: 449-54.
98. Chandrasekar D, Sistla R, Ahmad FJ, Khar RK, Diwan PV. Folate coupled poly(ethyleneglycol) conjugates of anionic poly(amidoamine) dendrimer for inflammatory tissue specific drug delivery. J Biomed Mater Res A. 2007;82:92-103.
99. Fand R, Tomalia DA. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today. 2001;6:427-36.
100. Han HJ, Lee YH, Park SH. Estradiol-17beta-BSA stimulates Ca(2+) uptake through nongenomic pathways in primary rabbit kidney proximal tubule cells: involvement of cAMP and PKC. J Cell Physiol. 2000;183:37-44.
101. Bulayeva NN, Gametchu B, Watson CS. Quantitative measurement of estrogen-induced ERK 1 and 2 activation via multiple membrane-initiated signaling pathways. Steroids. 2004;69:181-92.
102. Shiau AK, Barstad D, Loria PM, Cheng L, Kushner PJ, Agard DA, Greene GL. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 1998;95:927-37.
103. Coezy E, Borgna JL, Rochefort H. Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res. 1982;42:317-23.
104. Goodsell DS. The molecular perspective: tamoxifen and the estrogen receptor. Oncologist. 2002;7:163-64.
105. Li S, Wang AJ, Lai CK. Drug delivery system targeting to estrogen receptor over-expressed cells. US Patent: 7820204.
106. Torchilin VP. Nanoparticulates as pharmaceutical carriers. London, UK: Imperial College Press; 2006.
107. Cohen S, Bernstein H. Microparticulate systems for the delivery of proteins and vaccines. New York: Marcel Dekker; 1996.
108. Dreaden EC, Mwakwari SC, Sodji QH, Oyelere AK, El-Sayed MA. Tamoxifenpoly(ethylene glycol)-thiol gold nanoparticle conjugates: enhanced potency and selective delivery for breast cancer treatment. Bioconjug Chem. 2009;20:2247-53.
109. Sunders PT, Maguire SM, Gaughan J, Millar MR. Expression of oestrogen receptor beta (ER beta) in multiple rat tissues visualised by immunohistochemistry. J Endocr. 1997;154:R13-R16.
110. Makela S, Strauss L, Kuiper G, Valve E, Salmi S, Santti R, Gustafsson JA. Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. Mol Cell Endocrinol. 2000;170:219-29.
111. Chang WY, Prins GS. Estrogen receptor-beta: implications for the prostate gland. Prostate. 1999;40:115-23.
112. Komm BS, Terpening CM, Benz DJ, Graeme KA, Gallegos A, Korc M, Greene GL, O'Malley BW, Haussler MR. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science. 1988;241:81-84.
113. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL. Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology. 1999;140:4367-70.
114. Venkov CD, Rankin AB, Vaughan DE. Identification of authentic estrogen receptor in cultured endothelial cells. A potential mechanism for steroid hormone regulation of endothelial function. Circulation. 1996;94:727-33.
115. Lindner V, Kim SK, Karas RH, Kuiper GG, Gustafsson JA, Mendelsohn ME. Increased expression of estrogen receptor-beta mRNA in male blood vessels after vascular injury. Circ Res. 1998;83:224-29.
116. Simerly RB, Chang C, Muramatsu M, Swanson LW. Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. J Comp Neurol. 1990;294:76-95.
117. Shughrue PJ, Lubahn DB, Negro-Vilar A, Korach KS, Merchenthaler I. Responses in the brain of estrogen receptor alpha-disrupted mice. Proc Natl Acad Sci U S A. 1997;94:11008-12.
118. Gustafsson JA. Estrogen receptor beta-a new dimension in estrogen mechanism of action. J Endocrinol. 1999;163:379-83.
119. Ishiki N, Onishi H, Machida Y. Evaluation of antitumor and toxic side effects of mitomycin C-estradiol conjugates. Int J Pharm. 2004;279:81-93.
120. von-Schoultz E, Lundgren E, Henriksson R. Effects of estramustine and its constituents on human malignant glioma cells. Anticancer Res. 1990;10:693-96.
121. Matsudaira T, Kodo H, Okamoto S, Tani K, Tojo A, Ozawa K, Asano K, Asano S. The alloantigen-specific immunosuppressive activity of estradiol-chlorambucil conjugate (KM2210) and its beneficial effect on allogeneic bone marrow transplantation in mice. Transplantation. 1992;54:676-81.
122. McElvany KD, Carlson KE, Katzenellenbogen JA, Welch MJ. Factors affecting the target site uptake selectivity of estrogens radiopharmaceuticals: serum binding and endogenous estrogens. J Steroid Biochem. 1983;18:635-41.
123. James DA, Swamy N, Paz N, Hanson RN, Ray R. Synthesis and estrogen receptor binding affinity of a porphyrin-estradiol conjugate for targeted photodynamic therapy of cancer. Bioorg Med Chem Lett. 1999;16:2379-84.
124. Paliwal SR, Paliwal R, Pal HC, Saxena AK, Sharma PR, Gupta PN, Agrawal GP, Vyas SP. Estrogen-anchored pH-sensitive liposomes as nanomodule designed for site-specific delivery of doxorubicin in breast cancer therapy. Mol Pharm. 2012;9:176-86.