Lipid-based nanoparticles in the systemic delivery of siRNA

Nanomedicine

Volumn 9, Issue 1, 2014, Pages 105-120

  Lin, Qiaoya ^a,b,c   Chen, Juan ^a   Zhang, Zhihong ^a,c   Zheng, Gang ^a,b  

^a PRINCESS MARGARET HOSPITAL   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

Author keywords

lipid; lipoprotein; liposome; nanoparticle; RNAi; siRNA delivery; systemic delivery barrier

Indexed keywords

APOLIPOPROTEIN; NANOPARTICLE; SMALL INTERFERING RNA;

BIOCOMPATIBILITY; BLOOD FLOW; CYTOPLASM; DRUG RELEASE; DRUG STABILITY; DRUG UPTAKE; GENE TARGETING; HUMAN; LIPOSOMAL DELIVERY; NONHUMAN; PRIORITY JOURNAL; REVIEW; RNA BINDING; SYSTEMIC THERAPY; VASCULAR ENDOTHELIUM;

GENE TRANSFER TECHNIQUES; GENETIC THERAPY; HUMANS; LIPIDS; NANOPARTICLES; NEOPLASMS; RNA, SMALL INTERFERING; TREATMENT OUTCOME;

EID: 84896530178     PISSN: 17435889     EISSN: 17486963     Source Type: Journal    
DOI: 10.2217/nnm.13.192     Document Type: Review

References (122)

1. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391(6669), 806-811 (1998).
2. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411(6836), 494-498 (2001).
3. Whelan J. First clinical data on RNAi. Drug Discov. Today 10(15), 1014-1015 (2005).
4. Whitehead KA, Langer R, Anderson DG. Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8(2), 129-138 (2009).
5. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol. Pharm. 5(4), 505-515 (2008).
6. Bumcrot D, Manoharan M, Koteliansky V, Sah DW. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat. Chem. Biol. 2(12), 711-719 (2006).
7. Santel A, Aleku M, Keil O et al. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther. 13(16), 1222-1234 (2006).
8. van de Water FM, Boerman OC, Wouterse AC, Peters JG, Russel FG, Masereeuw R. Intravenously administered short interfering RNA accumulates in the kidney and selectively suppresses gene function in renal proximal tubules. Drug Metab. Dispos. 34(8), 1393-1397 (2006).
9. Takakura Y, Mahato RI, Hashida M. Extravasation of macromolecules. Adv. Drug Deliv. Rev. 34(1), 93-108 (1998).
10. Li W, Szoka FC Jr. Lipid-based nanoparticles for nucleic acid delivery. Pharm. Res. 24(3), 438-449 (2007).
11. Cabral H, Matsumoto Y, Mizuno K et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotechnol. 6(12), 815-823 (2011).
12. Pluen A, Boucher Y, Ramanujan S et al. Role of tumor-host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc. Natl Acad. Sci. USA 98(8), 4628-4633 (2001).
13. Stylianopoulos T, Poh MZ, Insin N et al. Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. Biophys. J. 99(5), 1342-1349 (2010).
14. Petros RA, Desimone JM. Strategies in the design of nanoparticles for therapeutic applications. Nat. Rev. Drug Discov. 9(8), 615-627 (2010).
15. Conner SD, Schmid SL. Regulated portals of entry into the cell. Nature 422(6927), 37-44 (2003).
16. Swanson JA, Watts C. Macropinocytosis. Trends Cell. Biol. 5(11), 424-428 (1995).
17. Bareford LM, Swaan PW. Endocytic mechanisms for targeted drug delivery. Adv. Drug Deliv. Rev. 59(8), 748-758 (2007).
18. Partlow KC, Lanza GM, Wickline SA. Exploiting lipid raft transport with membrane targeted nanoparticles: a strategy for cytosolic drug delivery. Biomaterials 29(23), 3367-3375 (2008).
19. Kunisawa J, Masuda T, Katayama K et al. Fusogenic liposome delivers encapsulated nanoparticles for cytosolic controlled gene release. J. Control. Release 105(3), 344-353 (2005).
20. Zhang Z, Cao W, Jin H et al. Biomimetic nanocarrier for direct cytosolic drug delivery. Angew. Chem. Int. Ed. Engl. 48(48), 9171-9175 (2009).
21. Akinc A, Zumbuehl A, Goldberg M et al. A combinatorial library of lipid-like materials for delivery of RNAi therapeutics. Nat. Biotechnol. 26(5), 561-569 (2008).
22. Wolfrum C, Shi S, Jayaprakash KN et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat. Biotechnol. 25(10), 1149-1157 (2007).
23. Morrissey DV, Lockridge JA, Shaw L et al. Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs. Nat. Biotechnol. 23(8), 1002-1007 (2005).
24. Semple SC, Akinc A, Chen J et al. Rational design of cationic lipids for siRNA delivery. Nat. Biotechnol. 28(2), 172-176 (2010).
25. Truong NP, Gu W, Prasadam I et al. An influenza virus-inspired polymer system for the timed release of siRNA. Nat. Commun. 4, 1902 (2013).
26. Yang XZ, Dou S, Wang YC et al. Single-step assembly of cationic lipid-polymer hybrid nanoparticles for systemic delivery of siRNA. ACS Nano 6(6), 4955-4965 (2012).
27. Dunn SS, Tian S, Blake S et al. Reductively responsive siRNA-conjugated hydrogel nanoparticles for gene silencing. J. Am. Chem. Soc. 134(17), 7423-7430 (2012).
28. Endo-Takahashi Y, Negishi Y, Nakamura A et al. pDNA-loaded Bubble liposomes as potential ultrasound imaging and gene delivery agents. Biomaterials 34(11), 2807-2813 (2013).
29. Suma T, Miyata K, Anraku Y et al. Smart multilayered assembly for biocompatible siRNA delivery featuring dissolvable silica, endosome-disrupting polycation, and detachable PEG. ACS Nano 6(8), 6693-6705 (2012).
30. McMahon KM, Mutharasan RK, Tripathy S et al. Biomimetic high density lipoprotein nanoparticles for nucleic acid delivery. Nano Lett. 11(3), 1208-1214 (2011).
31. Qi L, Gao X. Quantum dot-amphipol nanocomplex for intracellular delivery and real-time imaging of siRNA. ACS Nano 2(7), 1403-1410 (2008).
32. Lee JH, Lee K, Moon SH, Lee Y, Park TG, Cheon J. All-in-one target-cell-specific magnetic nanoparticles for simultaneous molecular imaging and siRNA delivery. Angew. Chem. Int. Ed. Engl. 48(23), 4174-4179 (2009).
33. Jiang S, Eltoukhy AA, Love KT, Langer R, Anderson DG. Lipidoid-coated iron oxide nanoparticles for efficient DNA and siRNA delivery. Nano Lett. 13(3), 1059-1064 (2013).
34. Posadas I, Guerra FJ, Cena V. Nonviral vectors for the delivery of small interfering RNAs to the CNS. Nanomedicine (Lond.) 5(8), 1219-1236 (2010).
35. Al-Jamal KT, Gherardini L, Bardi G et al. Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing. Proc. Natl Acad. Sci. USA 108(27), 10952-10957 (2011).
36. Lee H, Lytton-Jean AK, Chen Y et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 7(6), 389-393 (2012).
37. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29(4), 341-345 (2011).
38. Sorensen DR, Leirdal M, Sioud M. Gene silencing by systemic delivery of synthetic siRNAs in adult mice. J. Mol. Biol. 327(4), 761-766 (2003).
39. Sioud M, Sorensen DR. Cationic liposome-mediated delivery of siRNAs in adult mice. Biochem. Biophys. Res. Commun. 312(4), 1220-1225 (2003).
40. Ren T, Song YK, Zhang G, Liu D. Structural basis of DOTMA for its high intravenous transfection activity in mouse. Gene Ther. 7(9), 764-768 (2000).
41. Zhang S, Zhao B, Jiang H, Wang B, Ma B. Cationic lipids and polymers mediated vectors for delivery of siRNA. J. Control. Release 123(1), 1-10 (2007).
42. Kedmi R, Ben-Arie N, Peer D. The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation. Biomaterials 31(26), 6867-6875 (2010).
43. Tao W, Mao X, Davide JP et al. Mechanistically probing lipid-siRNA nanoparticle-associated toxicities identifies Jak inhibitors effective in mitigating multifaceted toxic responses. Mol. Ther. 19(3), 567-575 (2011).
44. Wasungu L, Hoekstra D. Cationic lipids, lipoplexes and intracellular delivery of genes. J. Control. Release 116(2), 255-264 (2006).
45. Li SD, Chen YC, Hackett MJ, Huang L. Tumor-targeted delivery of siRNA by self-assembled nanoparticles. Mol. Ther. 16(1), 163-169 (2008).
46. Aleku M, Schulz P, Keil O et al. Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 68(23), 9788-9798 (2008).
47. Santel A, Aleku M, Roder N et al. Atu027 prevents pulmonary metastasis in experimental and spontaneous mouse metastasis models. Clin. Cancer Res. 16(22), 5469-5480 (2010).
48. Buyens K, De Smedt SC, Braeckmans K et al. Liposome based systems for systemic siRNA delivery: stability in blood sets the requirements for optimal carrier design. J. Control. Release 158(3), 362-370 (2012).
49. Soutschek J, Akinc A, Bramlage B et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432(7014), 173-178 (2004).
50. Immordino ML, Dosio F, Cattel L. Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int. J. Nanomed. 1(3), 297-315 (2006).
51. Li SD, Huang L. Stealth nanoparticles: high density but sheddable PEG is a key for tumor targeting. J. Control. Release 145(3), 178-181 (2010).
52. Gomes-Da-Silva LC, Fonseca NA, Moura V, Pedroso de Lima MC, Simoes S, Moreira JN. Lipid-based nanoparticles for siRNA delivery in cancer therapy: paradigms and challenges. Acc. Chem. Res. 45(7), 1163-1171 (2012).
53. Sonoke S, Ueda T, Fujiwara K et al. Tumor regression in mice by delivery of Bcl-2 small interfering RNA with PEGylated cationic liposomes. Cancer Res. 68(21), 8843-8851 (2008).
54. Yagi N, Manabe I, Tottori T et al. A nanoparticle system specifically designed to deliver short interfering RNA inhibits tumor growth in vivo. Cancer Res. 69(16), 6531-6538 (2009).
55. Carmona S, Jorgensen MR, Kolli S et al. Controlling HBV replication in vivo by intravenous administration of triggered PEGylated siRNA-nanoparticles. Mol. Pharm. 6(3), 706-717 (2009).
56. Hatakeyama H, Akita H, Ito E et al. Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid. Biomaterials 32(18), 4306-4316 (2011).
57. Ishida T, Wang X, Shimizu T, Nawata K, Kiwada H. PEGylated liposomes elicit an anti-PEG IgM response in a T cell-independent manner. J. Control. Release 122(3), 349-355 (2007).
58. Gindy ME, Leone AM, Cunningham JJ. Challenges in the pharmaceutical development of lipid-based short interfering ribonucleic acid therapeutics. Expert Opin. Drug Deliv. 9(2), 171-182 (2012).
59. Chono S, Li SD, Conwell CC, Huang L. An efficient and low immunostimulatory nanoparticle formulation for systemic siRNA delivery to the tumor. J. Control. Release 131(1), 64-69 (2008).
60. Wang Y, Xu Z, Guo S et al. Intravenous delivery of siRNA targeting CD47 effectively inhibits melanoma tumor growth and lung metastasis. Mol. Ther. 21(10), 1919-1929 (2013).
61. Schlegel A, Bigey P, Dhotel H, Scherman D, Escriou V. Reduced in vitro and in vivo toxicity of siRNA-lipoplexes with addition of polyglutamate. J. Control. Release 165(1), 1-8 (2013).
62. Asai T, Matsushita S, Kenjo E et al. Dicetyl phosphate- tetraethylenepentamine-based liposomes for systemic siRNA delivery. Bioconjug. Chem. 22(3), 429-435 (2011).
63. Schlegel A, Largeau C, Bigey P et al. Anionic polymers for decreased toxicity and enhanced in vivo delivery of siRNA complexed with cationic liposomes. J. Control. Release 152(3), 393-401 (2011).
64. Zhang Y, Li H, Sun J et al. DC-Chol/DOPE cationic liposomes: a comparative study of the influence factors on plasmid pDNA and siRNA gene delivery. Int. J. Pharm. 390(2), 198-207 (2010).
65. Khoury M, Louis-Plence P, Escriou V et al. Efficient new cationic liposome formulation for systemic delivery of small interfering RNA silencing tumor necrosis factor a in experimental arthritis. Arthritis Rheum. 54(6), 1867-1877 (2006).
66. Courties G, Seiffart V, Presumey J et al. In vivo RNAi-mediated silencing of TAK1 decreases inflammatory Th1 and Th17 cells through targeting of myeloid cells. Blood 116(18), 3505-3516 (2010).
67. Courties G, Baron M, Presumey J et al. Cytosolic phospholipase A2a gene silencing in the myeloid lineage alters development of Th1 responses and reduces disease severity in collagen-induced arthritis. Arthritis Rheum. 63(3), 681-690 (2011).
68. Yang Y, Li J, Liu F, Huang L. Systemic delivery of siRNA via LCP nanoparticle efficiently inhibits lung metastasis. Mol. Ther. 20(3), 609-615 (2012).
69. Sato Y, Hatakeyama H, Sakurai Y, Hyodo M, Akita H, Harashima H. A pH-sensitive cationic lipid facilitates the delivery of liposomal siRNA and gene silencing activity in vitro and in vivo. J. Control. Release 163(3), 267-276 (2012).
70. Sakurai Y, Hatakeyama H, Sato Y, Hyodo M, Akita H, Harashima H. Gene silencing via RNAi and siRNA quantification in tumor tissue using MEND, a liposomal siRNA delivery system. Mol. Ther. 21(6), 1195-1203 (2013).
71. Mevel M, Kamaly N, Carmona S et al. DODAG; a versatile new cationic lipid that mediates efficient delivery of pDNA and siRNA. J. Control. Release 143(2), 222-232 (2010).
72. Daka A, Peer D. RNAi-based nanomedicines for targeted personalized therapy. Adv. Drug Deliv. Rev. 64(13), 1508-1521 (2012).
73. Ogris M, Wagner E. To be targeted: is the magic bullet concept a viable option for synthetic nucleic acid therapeutics? Hum. Gene Ther. 22(7), 799-807 (2011).
74. Tseng YC, Mozumdar S, Huang L. Lipid-based systemic delivery of siRNA. Adv. Drug Deliv. Rev. 61(9), 721-731 (2009).
75. Barros SA, Gollob JA. Safety profile of RNAi nanomedicines. Adv. Drug Deliv. Rev. 64(15), 1730-1737 (2012).
76. Zimmermann TS, Lee AC, Akinc A et al. RNAi-mediated gene silencing in non-human primates. Nature 441(7089), 111-114 (2006).
77. Tao W, Davide JP, Cai M et al. Noninvasive imaging of lipid nanoparticle-mediated systemic delivery of small-interfering RNA to the liver. Mol. Ther. 18(9), 1657-1666 (2010).
78. Judge AD, Robbins M, Tavakoli I et al. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice. J. Clin. Invest. 119(3), 661-673 (2009).
79. Geall AJ, Verma A, Otten GR et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109(36), 14604-14609 (2012).
80. Li L, Wang R, Wilcox D et al. Tumor vasculature is a key determinant for the efficiency of nanoparticle-mediated siRNA delivery. Gene Ther. 19(7), 775-780 (2012).
81. Rudorf S, Radler JO. Self-assembly of stable monomolecular nucleic acid lipid particles with a size of 30 nm. J. Am. Chem. Soc. 134(28), 11652-11658 (2012).
82. Gilleron J, Querbes W, Zeigerer A et al. Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31(7), 638-646 (2013).
83. Rensen PC, De Vrueh RL, Kuiper J, Bijsterbosch MK, Biessen EA, Van Berkel TJ. Recombinant lipoproteins: lipoprotein-like lipid particles for drug targeting. Adv. Drug Deliv. Rev. 47(2-3), 251-276 (2001).
84. Ng KK, Lovell JF, Zheng G. Lipoprotein-inspired nanoparticles for cancer theranostics. Acc. Chem. Res. 44(10), 1105-1113 (2011).
85. Jin HL, Chen J, Lovell JF, Zhang ZH, Zheng G. Synthesis and development of lipoprotein-based nanocarriers for light-activated theranostics. Israel J. Chem. 52(8-9), 715-727 (2012).
86. Krieger M. Charting the fate of the 'good cholesterol': identification and characterization of the high-density lipoprotein receptor SR-BI. Annu. Rev. Biochem. 68, 523-558 (1999).
87. Jin H, Lovell JF, Chen J et al. Mechanistic insights into LDL nanoparticle-mediated siRNA delivery. Bioconjug. Chem. 23(1), 33-41 (2012).
88. Kuwahara H, Nishina K, Yoshida K et al. Efficient in vivo delivery of siRNA into brain capillary endothelial cells along with endogenous lipoprotein. Mol. Ther. 19(12), 2213-2221 (2011).
89. Uno Y, Piao W, Miyata K, Nishina K, Mizusawa H, Yokota T. High-density lipoprotein facilitates in vivo delivery of a-tocopherol-conjugated short-interfering RNA to the brain. Hum. Gene Ther. 22(6), 711-719 (2011).
90. Lin Q, Chen J, Jin H et al. Efficient systemic delivery of siRNA by using high-density lipoprotein-mimicking peptide lipid nanoparticles. Nanomedicine (Lond.) 7(12), 1813-1825 (2012).
91. Mcconathy WJ, Nair MP, Paranjape S, Mooberry L, Lacko AG. Evaluation of synthetic/reconstituted high-density lipoproteins as delivery vehicles for paclitaxel. Anticancer Drugs 19(2), 183-188 (2008).
92. Kader A, Pater A. Loading anticancer drugs into HDL as well as LDL has little affect on properties of complexes and enhances cytotoxicity to human carcinoma cells. J. Control. Release 80(1-3), 29-44 (2002).
93. Yang M, Chen J, Cao W et al. Attenuation of nontargeted cell-kill using a high-density lipoprotein-mimicking peptide-phospholipid nanoscaffold. Nanomedicine (Lond.) 6(4), 631-641 (2011).
94. Yang M, Jin H, Chen J et al. Efficient cytosolic delivery of siRNA using HDL-mimicking nanoparticles. Small 7(5), 568-573 (2011).
95. Lin Q, Chen J, Ng KK, Cao W, Zhang Z, Zheng G. Imaging the cytosolic drug delivery mechanism of HDL-like nanoparticles. Pharm. Res. doi:10.1007/s11095- 013-1046-z (2013) (Epub ahead of print).
96. Ding Y, Wang W, Feng M et al. A biomimetic nanovector-mediated targeted cholesterol-conjugated siRNA delivery for tumor gene therapy. Biomaterials 33(34), 8893-8905 (2012).
97. Shahzad MM, Mangala LS, Han HD et al. Targeted delivery of small interfering RNA using reconstituted high-density lipoprotein nanoparticles. Neoplasia 13(4), 309-319 (2011).
98. Rui M, Tang H, Li Y, Wei X, Xu Y. Recombinant high density lipoprotein nanoparticles for target-specific delivery of siRNA. Pharm. Res. 30(5), 1203-1214 (2013).
99. Kim SI, Shin D, Choi TH et al. Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. Mol. Ther. 15(6), 1145-1152 (2007).
100. Nakayama T, Butler JS, Sehgal A et al. Harnessing a physiologic mechanism for siRNA delivery with mimetic lipoprotein particles. Mol. Ther. 20(8), 1582-1589 (2012).
101. Kong WH, Park K, Lee MY, Lee H, Sung DK, Hahn SK. Cationic solid lipid nanoparticles derived from apolipoprotein-free LDLs for target specific systemic treatment of liver fibrosis. Biomaterials 34(2), 542-551 (2013).
102. Akinc A, Goldberg M, Qin J et al. Development of lipidoid-siRNA formulations for systemic delivery to the liver. Mol. Ther. 17(5), 872-879 (2009).
103. Love KT, Mahon KP, Levins CG et al. Lipid-like materials for low-dose, in vivo gene silencing. Proc. Natl Acad. Sci. USA 107(5), 1864-1869 (2010).
104. Huang YH, Bao Y, Peng W et al. Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis. Proc. Natl Acad. Sci. USA 106(9), 3426-3430 (2009).
105. Nguyen DN, Mahon KP, Chikh G et al. Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery. Proc. Natl Acad. Sci. USA 109(14), E797-E803 (2012).
106. Kleinman ME, Yamada K, Takeda A et al. Sequence-and target-independent angiogenesis suppression by siRNA via TLR3. Nature 452(7187), 591-597 (2008).
107. Judge A, Maclachlan I. Overcoming the innate immune response to small interfering RNA. Hum. Gene Ther. 19(2), 111-124 (2008).
108. Robbins M, Judge A, Maclachlan I. siRNA and innate immunity. Oligonucleotides 19(2), 89-102 (2009).
109. Nguyen DN, Chen SC, Lu J et al. Drug delivery-mediated control of RNA immunostimulation. Mol. Ther. 17(9), 1555-1562 (2009).
110. Dolina JS, Sung SS, Novobrantseva TI, Nguyen TM, Hahn YS. Lipidoid nanoparticles containing PD-L1 siRNA delivered in vivo enter Kupffer cells and enhance NK and CD8+ T cell-mediated hepatic antiviral immunity. Mol. Ther. Nucleic Acids 2, e72 (2013).
111. Sahay G, Querbes W, Alabi C et al. Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31(7), 653-658 (2013).
112. Landen CN Jr, Chavez-Reyes A, Bucana C et al. Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery. Cancer Res. 65(15), 6910-6918 (2005).
113. Halder J, Kamat AA, Landen CN Jr et al. Focal adhesion kinase targeting using in vivo short interfering RNA delivery in neutral liposomes for ovarian carcinoma therapy. Clin. Cancer Res. 12(16), 4916-4924 (2006).
114. Verma A, Guha S, Diagaradjane P et al. Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer. Clin. Cancer Res. 14(8), 2476-2483 (2008).
115. Villares GJ, Zigler M, Wang H et al. Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA. Cancer Res. 68(21), 9078-9086 (2008).
116. Mangala LS, Zuzel V, Schmandt R et al. Therapeutic targeting of ATP7B in ovarian carcinoma. Clin. Cancer Res. 15(11), 3770-3780 (2009).
117. Chakravarty D, Roy SS, Babu CR et al. Therapeutic targeting of PELP1 prevents ovarian cancer growth and metastasis. Clin. Cancer Res. 17(8), 2250-2259 (2011).
118. Vivas-Mejia PE, Rodriguez-Aguayo C, Han HD et al. Silencing survivin splice variant 2B leads to antitumor activity in taxane-resistant ovarian cancer. Clin. Cancer Res. 17(11), 3716-3726 (2011).
119. Koldehoff M, Steckel NK, Beelen DW, Elmaagacli AH. Therapeutic application of small interfering RNA directed against bcr-abl transcripts to a patient with imatinib-resistant chronic myeloid leukaemia. Clin. Exp. Med. 7(2), 47-55 (2007).
120. Kapoor M, Burgess DJ. Efficient and safe delivery of siRNA using anionic lipids: formulation optimization studies. Int. J. Pharm. 432(1-2), 80-90 (2012).
121. Mckee TD, Chen J, Corbin I, Zheng G, Khokha R. Quantifying nanoparticle transport in vivo using hyperspectral imaging with a dorsal skinfold window chamber. J. Innovat. Opt. Health Sci. 5(4), (2012).
122. Zheng G, Chen J, Li H, Glickson JD. Rerouting lipoprotein nanoparticles to selected alternate receptors for the targeted delivery of cancer diagnostic and therapeutic agents. Proc. Natl Acad. Sci. USA 102(49), 17757-17762 (2005).