Drug delivery from engineered organisms and nanocarriers as monitored by multimodal imaging technologies

Daniel Calle, Duygu Yilmaz, Sebastian Cerdan, Armagan Kocer

1 Instituto de Investigaciones Biomédicas “Alberto Sols” CSIC/UAM, Madrid, Spain
2 Department of Neurosciences, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
§ Contributed equally

Received: , Accepted: , Published:

Topical Section: Protein Engineering

References

1. Bunker A, Magarkar A, Viitala T (2016) Rational design of liposomal drug delivery systems, a review: combined experimental and computational studies of lipid membranes, liposomes and their PEGylation. BBA Biomembranes 1858: 2334–2352.    

2. Mak IW, Evaniew N, Ghert M (2014) Lost in translation: animal models and clinical trials in cancer treatment. Am J Transl Res 6: 114–118.

3. Kopecek J (2010) Biomaterials and drug delivery: past, present, and future. Mol Pharm 7: 922–925.    

4. Goldstein DB (2003) Pharmacogenetics in the laboratory and the clinic. N Engl J Med 348: 553–556.    

5. Uetrecht J (2003) Screening for the potential of a drug candidate to cause idiosyncratic drug reactions. Drug Discov Today 8: 832–837.    

6. Lindon JC, Nicholson JK, Holmes E, et al. (2003) Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol Appl Pharm 187: 137–146.

7. Shaw LM, Kaplan B, Kaufman D (1996) Toxic effects of immunosuppressive drugs: mechanisms and strategies for controlling them. Clin Chem 42: 1316–1321.

8. Serajuddin A (1999) Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci 88: 1058–1066.    

9. Brodie BB (1962) Difficulties in extrapolating data on metabolism of drugs from animal to man. Clin Pharm Th 3: 374–380.    

10. Dedrick RL, Flessner MF (1997) Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer I 89: 480–487.

11. Bach PB (2009) Limits on medicare's ability to control rising spending on cancer drugs. N Engl J Med 360: 626–633.    

12. Vermeire E, Hearnshaw H, Van Royen P, et al. (2001) Patient adherence to treatment: three decades of research: a comprehensive review. J Clin Pharm Ther 26: 331–342.    

13. Cho EC, Glaus C, Chen J, et al. (2010) Inorganic nanoparticle-based contrast agents for molecular imaging. Trends Mol Med 16: 561–573.    

14. Dobrucki LW, Pan D, Smith AM (2015) Multiscale imaging of nanoparticle drug delivery. Curr Drug Targets 16: 560–570.    

15. Garcia J, Tang T, Louie AY (2015) Nanoparticle-based multimodal PET/MRI probes. Nanomedicine 10: 1343–1359.    

16. Janib SM, Moses AS, MacKay JA (2010) Imaging and drug delivery using theranostic nanoparticles. Adv Drug Deliver Rev 62: 1052–1063.    

17. Llovet JM, Real MI, Montaña X, et al. (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359: 1734–1739.    

18. Zhou X, Tang Z, Wang J, et al. (2014) Doxorubicin-eluting beads versus conventional transarterialchemoembolization for the treatment of hepatocellular carcinoma: a meta-analysis. Int J Clin Exp Med 7: 3892–3903.

19. Pawelek JM, Low KB, Bermudes D (2003) Bacteria as tumour-targeting vectors. Lancet Oncol 4: 548–556.    

20. King I, Bermudes D, Lin S, et al. (2004) Tumor-targeted salmonella expressing cytosine deaminase as an anticancer agent. Hum Gene Ther 13: 1225–1233.

21. Low KB, Ittensohn M, Le T, et al. (1999) Lipid a mutant salmonella with suppressed virulence and TNF-α induction retain tumor-targeting in vivo. Nat Biotechnol 17: 37–41.

22. Pawelek JM, Low KB, Bermudes D (1997) Tumor-targeted salmonella as a novel anticancer vector. Cancer Res 57: 4537–4544.

23. Schlechte H, Elbe B (1988) Recombinant plasmid DNA variation of clostridium oncolyticum- model experiments of cancerostatic gene transfer. Cent Sheet Bacteriol Microbiol Hyg Ser A 268: 347–356.

24. Sasaki T, Fujimori M, Hamaji Y, et al. (2006) Genetically engineered bifidobacterium longum for tumor-targeting enzyme-prodrug therapy of autochthonous mammary tumors in rats. Cancer Sci 97: 649–657.    

25. Panteli JT, Forbes NS (2016) Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses. Biotechnol Bioeng 113: 2474–2484.    

26. Hosseinidoust Z, Mostaghaci B, Yasa O, et al. (2016) Bioengineered and biohybrid bacteria-based systems for drug delivery. Adv Drug Deliver Rev 106: 27–44.    

27. Akin D, Sturgis J, Ragheb K, et al. (2007) Bacteria-mediated delivery of nanoparticles and cargo into cells. Nat Nanotechnol 2: 441–449.    

28. Edwards MR, Carlsen RW, Zhuang J, et al. (2014) Swimming characterization of serratia marcescens for bio-hybrid micro-robotics. J MicroBio Robot 9: 47–60.    

29. Zhuang J, Carlsen RW, Sitti M (2015) pH-taxis of biohybrid microsystems. Sci Rep 5: 11403–11415.    

30. Lee JB, Hong J, Bonner DK, et al. (2012) Self-assembled RNA interference microsponges for efficient siRNA delivery. Nat Mater 11: 316–322.    

31. Koudelka KJ, Pitek AS, Manchester M, et al. (2015) Virus-based nanoparticles as versatile nanomachines. Annu Rev Virol 2: 379–401.    

32. Douglas T, Young M (2006) Viruses: making friends with old foes. Science 312: 873–875.    

33. Esfandiari N, Arzanani MK, Soleimani M, et al. (2015) A new application of plant virus nanoparticles as drug delivery in breast cancer. Tumor Biol 37: 1229–1236.

34. Cheng F, Tsvetkova IB, Khuong YL, et al. (2013) The packaging of different cargo into enveloped viral nanoparticles. Mol Pharm 10: 51–58.    

35. Steinmetz NF, Mertens ME, Taurog RE, et al. (2010) Potato virus x as a novel platform for potential biomedical applications. Nano Lett 10: 305–312.    

36. Aljabali AAA, Shukla S, Lomonossoff GP, et al. (2013) CPMV-DOX delivers. Mol Pharm 10: 3–10.    

37. Galaway FA, Stockley PG (2013) MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform. Mol Pharm 10: 59–68.    

38. Choi KM, Choi SH, Jeon H, et al. (2011) Chimeric capsid protein as a nanocarrier for siRNA delivery: stability and cellular uptake of encapsulated siRNA. Acs Nano 5: 8690–8699.    

39. Choi KM, Kim K, Kwon IC, et al. (2013) Systemic delivery of siRNA by chimeric capsid protein: tumor targeting and RNAi activity in vivo. Mol Pharm 10: 18–25.    

40. Kim KR, Kim DR, Lee T, et al. (2013) Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells. Chem Commun 49: 2010–2012.    

41. Jiang Q, Song C, Nangreave J, et al. (2012) DNA origami as a carrier for circumvention of drug resistance. J Am Chem Soc 134: 13396–13403.    

42. Charoenphol P, Bermudez H (2014) Design and application of multifunctional DNA nanocarriers for therapeutic delivery. Acta Biomater 10: 1683–1691.

43. Kumar V, Palazzolo S, Bayda S, et al. (2016) DNA nanotechnology for cancer therapy. Theranostics 6: 710–725.    

44. Angell C, Xie S, Zhang L, et al. (2016) DNA nanotechnology for precise control over drug delivery and gene therapy. Small 12: 1117–1132.    

45. Taylor AI, Beuron F, Peak CSY, et al. (2016) Nanostructures from synthetic genetic polymers. Chembiochem 17: 1107–1110.    

46. Kim KR, Kim HY, Lee YD, et al. (2016) Self-assembled mirror DNA nanostructures for tumor-specific delivery of anticancer drugs. J Control Release 243: 121–131.    

47. Kim KR, Lee T, Kim BS, et al. (2014) Utilizing the bioorthogonal base-pairing system of l-DNA to design ideal DNA nanocarriers for enhanced delivery of nucleic acid cargos. Chem Sci 5: 1533–1537.    

48. Bangham AD, Standish MM, Watkins JC (1965) Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 13: 238–IN27.    

49. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303: 1818–1822.    

50. Pattni BS, Chupin VV, Torchilin VP (2015) New developments in liposomal drug delivery. Chem Rev 115: 10938–10966.    

51. Leung SJ, Romanowski M (2012) Light-activated content release from liposomes. Theranostics 2: 1020–1036.    

52. Ng LT, Yuba E, Kono K (2009) Modification of liposome surface with pH-responsive polyampholytes for the controlled-release of drugs. Res Chem Intermediat 35: 1015–1025.    

53. Obata Y, Tajima S, Takeoka S (2010) Evaluation of pH-responsive liposomes containing amino acid-based zwitterionic lipids for improving intracellular drug delivery in vitro and in vivo. J Control Release 142: 267–276.    

54. Landon CD, Park JY, Needham D, et al. (2011) Nanoscale drug delivery and hyperthermia: the materials design and preclinical and clinical testing of low temperature-sensitive liposomes used in combination with mild hyperthermia in the treatment of local cancer. Open Nanomed J 3: 38–64.

55. Stubbs M, McSheehy PM, Griffiths JR (1999) Causes and consequences of acidic pH in tumors: a magnetic resonance study. Adv Enzyme Regul 39: 13–30.    

56. Zhang J, Tao W, Chen Y, et al. (2015) Doxorubicin-loaded star-shaped copolymer PLGA-vitamin E tpgs nanoparticles for lung cancer therapy. J Mater Sci Mater M 26: 165.    

57. Kocer A (2007) A remote controlled valve in liposomes for triggered liposomal release. J Liposome Res 17: 219–225.    

58. Kocer A, Walko M, Bulten E, et al. (2006) Rationally designed chemical modulators convert a bacterial channel protein into a pH-sensory valve. Angew Chem Int Edit 45: 3126–3130.    

59. Kocer A, Walko M, Meijberg W, et al. (2005) A light-actuated nanovalve derived from a channel protein. Science 309: 755–758.    

60. Pacheco TJ, Mukherjee N, Walko M, et al. (2015) Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model. Nanomedicine 11: 1345–1354.

61. Shriver LP, Koudelka KJ, Manchester M (2009) Viral nanoparticles associate with regions of inflammation and blood brain barrier disruption during CNS infection. J Neuroimmunol 211: 66–72.    

62. Rae CS, Khor IW, Wang Q, et al. (2005) Systemic trafficking of plant virus nanoparticles in mice via the oral route. Virology 343: 224–235.    

63. Lewis JD, Destito G, Zijlstra A, et al. (2006) Viral nanoparticles as tools for intravital vascular imaging. Nat Med 12: 354–360.    

64. Leong HS, Steinmetz NF, Ablack A, et al. (2010) Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Nat Protoc 5: 1406–1417.    

65. Manchester M, Singh P (2006) Virus-based nanoparticles (VNPs): platform technologies for diagnostic imaging. Adv Drug Deliver Rev 58: 1505–1522.    

66. Cheng F, Mukhopadhyay S (2011) Generating enveloped virus-like particles with in vitro assembled cores. Virology 413: 153–160.    

67. Weissleder R, Mahmood U (2001) Molecular imaging. Radiology 219: 316–333.    

68. Bao G, Mitragotri S, Tong S (2013) Multifunctional nanoparticles for drug delivery and molecular imaging. Annu Rev Biomed Eng 15: 253–282.    

69. Ding H, Wu F (2012) Image guided biodistribution of drugs and drug delivery. Theranostics 2: 1037–1039.    

70. Brys AK, Gowda R, Loriaux DB, et al. (2016) Nanotechnology-based strategies for combating toxicity and resistance in melanoma therapy. Biotechnol Adv 34: 565–577.    

71. Gowda R, Jones NR, Banerjee S, et al. (2013) Use of nanotechnology to develop multi-drug inhibitors for cancer therapy. J Nanomed Nanotechnol 4: 184.

72. Medina FJL, Giulianotti MA, Welmaker GS, et al. (2013) Shifting from the single to the multitarget paradigm in drug discovery. Drug Discov Today 18: 495–501.    

73. Yuan Y, Cai T, Xia X, et al. (2016) Nanoparticle delivery of anticancer drugs overcomes multidrug resistance in breast cancer. Drug Deliv 23: 3350–3357.    

74. Zheng H, Fridkin M, Youdim M (2014) From single target to multitarget/network therapeutics in Alzheimer's therapy. Pharmaceuticals 7: 113–135.    

75. Pawar S, Shevalkar G, Vavia P (2016) Glucosamine-anchored doxorubicin-loaded targeted nano-niosomes: pharmacokinetic, toxicity and pharmacodynamic evaluation. J Drug Target 24: 730–743.

76. Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33: 941–951.    

77. Shin TH, Choi Y, Kim S, et al. (2015) Recent advances in magnetic nanoparticle-based multi-modal imaging. Chem Soc Rev 44: 4501–4516.    

78. Johnsen KB, Moos T (2016) Revisiting nanoparticle technology for blood-brain barrier transport: unfolding at the endothelial gate improves the fate of transferrin receptor-targeted liposomes. J Control Release 222: 32–46.    

79. Grabrucker AM, Ruozi B, Belletti D, et al. (2016) Nanoparticle transport across the blood brain barrier. Tissue Barriers 4: e1153568–e1153571.    

80. Ho D, Wang C-HK, Chow EKH (2015) Nanodiamonds: the intersection of nanotechnology, drug development, and personalized medicine. Sci Adv 1: e1500439–e1500439.

81. Webb S (1988) The physics of medical imaging, CRC Press.

82. Farncombe T, Iniewsky K (2013) Medical imaging: technology ad applications, CRC Press, 732.

83. Caravan P, Ellison JJ, McMurry TJ, et al. (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99: 2293–2352.    

84. Pavel DG, Zimmer M, Patterson VN (1977) In vivo labeling of red blood cells with 99mTc: a new approach to blood pool visualization. J Nucl Med 18: 305–308.

85. Hahn MA, Singh AK, Sharma P, et al. (2011) Nanoparticles as contrast agents for in-vivo bioimaging: current status and future perspectives. Anal Bioanal Chem 399: 3–27.    

86. Chakravarty R, Hong H, Cai W (2014) Positron emission tomography image-guided drug delivery: current status and future perspectives. Mol Pharm 11: 3777–3797.    

87. de Smet M, Langereis S, van den Bosch S et al. (2013) SPECT/CT imaging of temperature-sensitive liposomes for MR-image guided drug delivery with high intensity focused ultrasound. J Control Release 169: 82–90.

88. Gao X, Cui Y, Levenson RM, et al. (2004) In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22: 969–976.    

89. Weissleder R, Tung CH, Mahmood U, et al. (1999) In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 17: 375–378.    

90. Calle D, Negri V, Ballesteros P, et al. (2015) Magnetoliposomes loaded with poly-unsaturated fatty acids as novel theranostic anti-inflammatory formulations. Theranostics 5: 489–503.    

91. Heinle SK, Noblin J, Goree BP, et al. (2000) Assessment of myocardial perfusion by harmonic power doppler imaging at rest and during adenosine stress: comparison with (99 m) Tc-sestamibi SPECT imaging. Circulation 102: 55–60.    

92. Urtasun RC, Parliament MB, McEwan AJ, et al. (1996) Measurement of hypoxia in human tumours by non-invasive spect imaging of iodoazomycin arabinoside. Brit J Cancer Suppl 27: S209–S212.

93. Leitha T, Glaser C, Pruckmayer M, et al. (1998) Technetium-99m-MIBI in primary and recurrent head and neck tumors: contribution of bone SPECT image fusion. J Nucl Med 39: 1166–1171.

94. Tharp K, Israel O, Hausmann J, et al. (2004) Impact of 131I-SPECT/CT images obtained with an integrated system in the follow-up of patients with thyroid carcinoma. Eur J Nucl Med Mol I 31: 1435–1442.

95. Fukuyama H, Ouchi Y, Matsuzaki S, et al. (1997) Brain functional activity during gait in normal subjects: a SPECT study. Neurosci Lett 228: 183–186.    

96. Rudin M, Weissleder R (2003) Molecular imaging in drug discovery and development. Nat Rev Drug Discov 2: 123–131.    

97. Bushberg JT, Boone JM (2011) The essential physics of medical imaging, Lippincott Williams & Wilkins.

98. Finnema SJ, Scheinin M, Shahid M, et al. (2015) Application of cross-species PET imaging to assess neurotransmitter release in brain. Psychopharmacology 232: 4129–4157.    

99. Haubner R, Maschauer S, Prante O (2014) PET radiopharmaceuticals for imaging integrin expression: tracers in clinical studies and recent developments. Biomed Res Int 2014: 871609–871617.

100. Tateishi U, Oka T, Inoue T (2012) Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers. Curr Med Chem 19: 3301–3309.    

101. Wagner S, Breyholz HJ, Law MP, et al. (2007) Novel fluorinated derivatives of the broad-spectrum MMP inhibitors N-hydroxy-2(R)-[[(4-methoxyphenyl)sulfonyl](benzyl)- and (3-picolyl)-amino]-3-methyl-butanamide as potential tools for the molecular imaging of activated MMPs with PET. J Med Chem 50: 5752–5764.    

102. Stacy MR, Maxfield MW, Sinusas AJ (2012) Targeted molecular imaging of angiogenesis in PET and SPECT: a review. Yale J Biol Med 85: 75–86.

103. Ripa RS, Pedersen SF, Kjaer A (2016) PET/MR imaging in vascular disease atheroscleroaia and inflammation. Positron Emission Tomo 11: 479–488.

104. Wu C, Li F, Niu G, et al. (2013) PET imaging of inflammation biomarkers. Theranostics 3: 448–466.    

105. Pacheco TJ, Calle D, Lizarbe B, et al. (2011) Environmentally sensitive paramagnetic and diamagnetic contrast agents for nuclear magnetic resonance imaging and spectroscopy. Curr Top Med Chem 11: 115–130.    

106. Lanza GM, Moonen C, Baker JR, et al. (2013) Assessing the barriers to image-guided drug delivery. WIRE Nanomed Nanobiotechnol 6: 1–14.

107. Na HB, Song IC, Hyeon T (2009) Inorganic nanoparticles for MRI contrast agents. Adv Mater 21: 2133–2148.

108. Bonnemain B (1998) Superparamagnetic agents in magnetic resonance imaging: physicochemical characteristics and clinical applications: a review. J Drug Target 6: 167–174.    

109. Yu Y, Sun D (2010) Superparamagnetic iron oxide nanoparticle "theranostics" for multimodality tumor imaging, gene delivery, targeted drug and prodrug delivery. Expert Rev Clin Pharmaco 3: 117–130.    

110. Liu F, Laurent S, Fattahi H, et al. (2011) Superparamagnetic nanosystems based on iron oxide nanoparticles for biomedical imaging. Nanomedicine 6: 519–528.    

111. Al-Nahhas A, Win Z, Singh Q, et al. (2006) The role of 18F-FDG PET in oncology: clinical and resource implications. Nucl Med Rev Cent East Eur 9: 1–5.

112. Chopra A (2004) 18F-Labeled N-succinimidyl-4-fluorobenzoate-conjugated rat anti-mouse vascular endothelial growth factor receptor 2 monoclonal antibody linked to microbubbles, MICAD.

113. Gupta H, Aqil M, Khar RK, et al. (2010) Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery. Nanomedicine 6: 324–333.

114. Luo Q, Zhao J, Zhang X, et al. (2011) Nanostructured lipid carrier (NLC) coated with chitosan oligosaccharides and its potential use in ocular drug delivery system. Int J Pharm 403: 185–191.    

115. Möller W, Schuschnig U, Celik G, et al. (2013) Topical drug delivery in chronic rhinosinusitis patients before and after sinus surgery using pulsating aerosols. Plos One 8: e74991.    

116. Gallamini A, Zwarthoed C, Borra A (2014) Positron emission tomography (PET) in oncology. Cancers 6: 1821–1889.    

117. Xiao Y, Hong H, Javadi A, et al. (2012) Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging. Biomaterials 33: 3071–3082.    

118. Guo J, Hong H, Chen G, et al. (2014) Theranostic unimolecular micelles based on brush-shaped amphiphilic block copolymers for tumor-targeted drug delivery and positron emission tomography imaging. Acs Appl Mater Interface 6: 21769–21779.    

119. Hong H, Zhang Y, Engle JW, et al. (2012) In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene. Biomaterials 33: 4147–4156.    

120. Liu Z, Cal W, He L, et al. (2007) In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol 2: 47–52.    

121. Blasberg RG (2003) In vivo molecular-genetic imaging: multi-modality nuclear and optical combinations. Nucl Med Biol 30: 879–888.    

122. Hoffman RM (2015) Application of GFP imaging in cancer. Lab Invest 95: 432–452.    

123. Kocher B, Piwnica WD (2013) Illuminating cancer systems with genetically engineered mouse models and coupled luciferase reporters in vivo. Cancer Discov 3: 616–629.

124. Wang C, Cheng L, Liu Z (2011) Drug delivery with upconversion nanoparticles for multi-functional targeted cancer cell imaging and therapy. Biomaterials 32: 1110–1120.    

125. Yuan Y, Liu B (2014) Self-assembled nanoparticles based on PEGylated conjugated polyelectrolyte and drug molecules for image-guided drug delivery and photodynamic therapy. Acs Appl Mater Interface 6: 14903–14910.    

126. Cool SK, Geers B, Roels S, et al. (2013) Coupling of drug containing liposomes to microbubbles improves ultrasound triggered drug delivery in mice. J Control Release 172: 885–893.

127. Chen ML, He YJ, Chen XW, et al. (2012) Quantum dots conjugated with Fe₃O₄-filled carbon nanotubes for cancer-targeted imaging and magnetically guided drug delivery. Langmuir 28: 16469–16476.

128. Sun X, Liu Z, Welsher K, et al. (2008) Nano-graphene oxide for cellular imaging and drug delivery. Nano Res 1: 203–212.    

129. Shen Z, Wu A, Chen X (2016) Iron oxide nanoparticle based contrast agents for magnetic resonance imaging. Mol Pharm, DOI: 10.1021/acs.molpharmaceut.6b00839.

130. Hermann P, Kotek J, Kubíček V, et al. (2008) Gadolinium(III) complexes as MRI contrast agents : ligand design and properties of the complexes. Dalton Trans 23: 3027–3047.

131. Kaida S, Cabral H, Kumagai M, et al. (2010) Visible drug delivery by supramolecular nanocarriers directing to single-platformed diagnosis and therapy of pancreatic tumor model. Cancer Res 70: 7031–7041.    

132. Negussie AH, Yarmolenko PS, Partanen A, et al. (2011) Formulation and characterisation of magnetic resonance imageable thermally sensitive liposomes for use with magnetic resonance-guided high intensity focused ultrasound. Int J Hyperther 27: 140–155.    

133. Tagami T, Foltz WD, Ernsting MJ, et al. (2011) MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome. Biomaterials 32: 6570–6578.    

134. Ma X, Tao H, Yang K, et al. (2012) A functionalized graphene oxide-iron oxide nanocomposite for magnetically targeted drug delivery, photothermal therapy, and magnetic resonance imaging. Nano Res 5: 199–212.    

135. Al-Jamal WT, Kostarelos K (2007) Liposome-nanoparticle hybrids for multimodal diagnostic and therapeutic applications. Nanomedicine 2: 85–98.    

136. Mikhaylov G, Mikac U, Magaeva AA, et al. (2011) Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat Nanotechnol 6: 594–602.    

137. Xu H, Cheng L, Wang C, et al. (2011) Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery. Biomaterials 32: 9364–9373.    

138. Yang X, Hong H, Grailer JJ, et al. (2011) cRGD-functionalized, DOX-conjugated, and ⁶⁴Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials 32: 4151–4160.    

139. Claesen J, Fischbach MA (2015) Synthetic microbes as drug delivery systems. Acs Synth Biol 4: 358–364.    

140. Sotoudeh H, Sharma A, Fowler KJ, et al. (2016) Clinical application of PET/MRI in oncology. J Magn Reson Imaging 44: 265–276.    

141. Pan D, Caruthers SD, Chen J, et al. (2010) Nanomedicine strategies for molecular targets with MRI and optical imaging. Future Med Chem 2: 471–490.    

142. Culver J, Akers W, Achilefu S (2008) Multimodality molecular imaging with combined optical and SPECT/PET modalities. J Nucl Med 49: 169–172.    

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