Overview of nano-drugs characteristics for clinical application: the journey from the entry to the exit point
Source abstract
Abstract
The ever-increasing number of diseases worldwide requires comprehensive, efficient, and cost-effective modes of treatments. Among various strategies, nanomaterials fulfill most of these criteria. The unique physicochemical properties of nanoparticles have made them a premier choice as a drug or a drug delivery system for the purpose of treatment, and as bio-detectors for disease prognosis. However, the main challenge is the proper consideration of the physical properties of these nanomaterials, while developing them as potential tools for therapeutics and/or diagnostics. In this review, we focus mainly on the characteristics of nanoparticles to develop an effective and sensitive system for clinical purposes. This review will present an overview of the important properties of nanoparticles, through their journey from its route of administration until disposal from the human body after accomplishing targeted functionality. We have chosen cancer as our model disease to explain the potentiality of nano-systems for therapeutics and diagnostics in relation to several organs (intestine, lung, brain, etc.). Furthermore, we have discussed their biodegradability and accumulation probability which can cause unfavorable side effects in healthy human subjects.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Nanoparticle-Based Drug Delivery · Nanoparticles: synthesis and applications · Graphene and Nanomaterials Applications
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (100+)
Show source-provided references
1. Aktas Y, Yemisci M, Andrieux K, Gursoy RN, Alonso MJ, Fernandez-Megia E, Novoa-Carballal R, Quinoa E, Riguera R, Sargon MF, Celik HH, Demir AS, Hincal AA, Dalkara T, Capan Y, Couvreur P (2005) Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26. Bioconjug Chem 16(6):1503–1511. doi: 10.1021/bc050217o10.1021/bc050217o ↗
2. Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P (2012) A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging 2012:940585. doi: 10.1155/2012/94058510.1155/2012/940585 ↗
3. Albanese A, Tang PS, Chan WC (2012) The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annu Rev Biomed Eng 14:1–16. doi: 10.1146/annurev-bioeng-071811-15012410.1146/annurev-bioeng-071811-150124 ↗
4. Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5(4):505–515. doi: 10.1021/mp800051m10.1021/mp800051m ↗
5. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48. doi: 10.1016/j.addr.2012.09.03710.1016/j.addr.2012.09.037 ↗
6. Amin ML (2013) P-glycoprotein inhibition for optimal drug delivery. Drug target insights 7:27–34. doi: 10.4137/DTI.S1251910.4137/DTI.S12519 ↗
7. Azarmi S, Tao X, Chen H, Wang Z, Finlay WH, Lobenberg R, Roa WH (2006) Formulation and cytotoxicity of doxorubicin nanoparticles carried by dry powder aerosol particles. Int J Pharm 319(1–2):155–161. doi: 10.1016/j.ijpharm.2006.03.05210.1016/j.ijpharm.2006.03.052 ↗
8. Badr CE, Tannous BA (2011) Bioluminescence imaging: progress and applications. Trends Biotechnol 29(12):624–633. doi: 10.1016/j.tibtech.2011.06.01010.1016/j.tibtech.2011.06.010 ↗
9. Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153(3):198–205. doi: 10.1016/j.jconrel.2011.06.00110.1016/j.jconrel.2011.06.001 ↗
10. Baker GL, Gupta A, Clark ML, Valenzuela BR, Staska LM, Harbo SJ, Pierce JT, Dill JA (2008) Inhalation toxicity and lung toxicokinetics of C60 fullerene nanoparticles and microparticles. Toxicol Sci 101(1):122–131. doi: 10.1093/toxsci/kfm24310.1093/toxsci/kfm243 ↗
11. Banerjee D, Harfouche R, Sengupta S (2011) Nanotechnology-mediated targeting of tumor angiogenesis. Vasc Cell 3(1):3. doi: 10.1186/2045-824X-3-310.1186/2045-824X-3-3 ↗
12. Barone PW, Yoon H, Ortiz-Garcia R, Zhang J, Ahn JH, Kim JH, Strano MS (2009) Modulation of single-walled carbon nanotube photoluminescence by hydrogel swelling. ACS Nano 3(12):3869–3877. doi: 10.1021/nn901025x10.1021/nn901025x ↗
13. Barreto JA, O’Malley W, Kubeil M, Graham B, Stephan H, Spiccia L (2011) Nanomaterials: applications in cancer imaging and therapy. Adv Mater 23(12):H18–H40. doi: 10.1002/adma.20110014010.1002/adma.201100140 ↗
14. Batrakova EV, Li S, Reynolds AD, Mosley RL, Bronich TK, Kabanov AV, Gendelman HE (2007) A macrophage-nanozyme delivery system for Parkinson’s disease. Bioconjugate chemistry 18(5):1498–1506. doi: 10.1021/bc700184b10.1021/bc700184b ↗
15. Bayindir ZS, Yuksel N (2010) Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery. J Pharm Sci 99(4):2049–2060. doi: 10.1002/jps.2194410.1002/jps.21944 ↗
16. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC (2014) Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev 66:2–25. doi: 10.1016/j.addr.2013.11.00910.1016/j.addr.2013.11.009 ↗
17. Bisht S, Mizuma M, Feldmann G, Ottenhof NA, Hong SM, Pramanik D, Chenna V, Karikari C, Sharma R, Goggins MG, Rudek MA, Ravi R, Maitra A, Maitra A (2010) Systemic administration of polymeric nanoparticle-encapsulated curcumin (NanoCurc) blocks tumor growth and metastases in preclinical models of pancreatic cancer. Mol Cancer Ther 9(8):2255–2264. doi: 10.1158/1535-7163.MCT-10-017210.1158/1535-7163.MCT-10-0172 ↗
18. Cai S, Vijayan K, Cheng D, Lima EM, Discher DE (2007) Micelles of different morphologies—advantages of worm-like filomicelles of PEO–PCL in paclitaxel delivery. Pharm Res 24(11):2099–2109. doi: 10.1007/s11095-007-9335-z10.1007/s11095-007-9335-z ↗
19. Camp ER, Wang C, Little EC, Watson PM, Pirollo KF, Rait A, Cole DJ, Chang EH, Watson DK (2013) Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy. Cancer Gene Ther 20(4):222–228. doi: 10.1038/cgt.2013.910.1038/cgt.2013.9 ↗
20. Champion JA, Mitragotri S (2006) Role of target geometry in phagocytosis. Proc Natl Acad Sci USA 103(13):4930–4934. doi: 10.1073/pnas.060099710310.1073/pnas.0600997103 ↗
21. Chen H, Kim S, He W, Wang H, Low PS, Park K, Cheng JX (2008) Fast release of lipophilic agents from circulating PEG–PDLLA micelles revealed by in vivo forster resonance energy transfer imaging. Langmuir 24(10):5213–5217. doi: 10.1021/la703570m10.1021/la703570m ↗
22. Chipman SD, Oldham FB, Pezzoni G, Singer JW (2006) Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomed 1(4):375–38310.2147/nano.2006.1.4.375 ↗
23. Cho WS, Cho M, Kim SR, Choi M, Lee JY, Han BS, Park SN, Yu MK, Jon S, Jeong J (2009) Pulmonary toxicity and kinetic study of Cy5.5-conjugated superparamagnetic iron oxide nanoparticles by optical imaging. Toxicol Appl Pharmacol 239(1):106–115. doi: 10.1016/j.taap.2009.05.02610.1016/j.taap.2009.05.026 ↗
24. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Itty Ipe B, Bawendi MG, Frangioni JV (2007) Renal clearance of quantum dots. Nat Biotechnol 25(10):1165–1170. doi: 10.1038/nbt134010.1038/nbt1340 ↗
25. Choi CH, Zuckerman JE, Webster P, Davis ME (2011) Targeting kidney mesangium by nanoparticles of defined size. Proc Natl Acad Sci USA 108(16):6656–6661. doi: 10.1073/pnas.110357310810.1073/pnas.1103573108 ↗
26. Czarnobaj K (2008) Preparation and characterization of silica xerogels as carriers for drugs. Drug Deliv 15(8):485–492. doi: 10.1080/1071754080232149510.1080/10717540802321495 ↗
27. Davis ME (2009a) Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin. Adv Drug Deliv Rev 61(13):1189–1192. doi: 10.1016/j.addr.2009.05.00510.1016/j.addr.2009.05.005 ↗
28. Davis ME (2009b) The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm 6(3):659–668. doi: 10.1021/mp900015y10.1021/mp900015y ↗
29. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A (2010) Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464(7291):1067–1070. doi: 10.1038/nature0895610.1038/nature08956 ↗
30. De Jong WH, Borm PJ (2008) Drug delivery and nanoparticles: applications and hazards. Int J Nanomed 3(2):133–14910.2147/IJN.S596 ↗
31. Decuzzi P, Godin B, Tanaka T, Lee SY, Chiappini C, Liu X, Ferrari M (2010) Size and shape effects in the biodistribution of intravascularly injected particles. J Control Release 141(3):320–327. doi: 10.1016/j.jconrel.2009.10.01410.1016/j.jconrel.2009.10.014 ↗
32. Di Pasqua AJ, Wallner S, Kerwood DJ, Dabrowiak JC (2009) Adsorption of the Pt(II) anticancer drug carboplatin by mesoporous silica. Chem Biodivers 6(9):1343–1349. doi: 10.1002/cbdv.20090002110.1002/cbdv.200900021 ↗
33. Ding HM, Ma YQ (2013) Controlling cellular uptake of nanoparticles with pH-sensitive polymers. Sci Rep 3:2804. doi: 10.1038/srep0280410.1038/srep02804 ↗
34. Elsabahy M, Wooley KL (2012) Design of polymeric nanoparticles for biomedical delivery applications. Chem Soc Rev 41(7):2545–2561. doi: 10.1039/c2cs15327k10.1039/c2cs15327k ↗
35. Eom HJ, Choi J (2009) Oxidative stress of silica nanoparticles in human bronchial epithelial cell, Beas-2B. Toxicol In Vitro 23(7):1326–1332. doi: 10.1016/j.tiv.2009.07.01010.1016/j.tiv.2009.07.010 ↗
36. Faraji AH, Wipf P (2009) Nanoparticles in cellular drug delivery. Bioorg Med Chem 17(8):2950–2962. doi: 10.1016/j.bmc.2009.02.04310.1016/j.bmc.2009.02.043 ↗
37. Fenton PJ (1965) Applanation tonometry using one drop of an anaesthetic-fluorescein mixture. Br J Ophthalmol 49:205–20810.1136/bjo.49.4.205 ↗
38. Fernandez-Suarez M, Ting AY (2008) Fluorescent probes for super-resolution imaging in living cells. Nat Rev Mol Cell Biol 9(12):929–943. doi: 10.1038/nrm253110.1038/nrm2531 ↗
39. Foulds PG, Mitchell JD, Parker A, Turner R, Green G, Diggle P, Hasegawa M, Taylor M, Mann D, Allsop D (2011) Phosphorylated alpha-synuclein can be detected in blood plasma and is potentially a useful biomarker for Parkinson’s disease. FASEB J 25(12):4127–4137. doi: 10.1096/fj.10-17919210.1096/fj.10-179192 ↗
40. Gao X, Tao W, Lu W, Zhang Q, Zhang Y, Jiang X, Fu S (2006) Lectin-conjugated PEG–PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials 27(18):3482–3490. doi: 10.1016/j.biomaterials.2006.01.03810.1016/j.biomaterials.2006.01.038 ↗
41. Gindy ME, Prud’homme RK (2009) Multifunctional nanoparticles for imaging, delivery and targeting in cancer therapy. Expert Opin Drug Deliv 6(8):865–878. doi: 10.1517/1742524090293290810.1517/17425240902932908 ↗
42. Gullotti E, Yeo Y (2009) Extracellularly activated nanocarriers: a new paradigm of tumor targeted drug delivery. Mol Pharm 6(4):1041–1051. doi: 10.1021/mp900090z10.1021/mp900090z ↗
43. Guterres SS, Alves MP, Pohlmann AR (2007) Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug target insights 2:147–15710.1177/117739280700200002 ↗
44. Harasym TO, Tardi PG, Harasym NL, Harvie P, Johnstone SA, Mayer LD (2007) Increased preclinical efficacy of irinotecan and floxuridine coencapsulated inside liposomes is associated with tumor delivery of synergistic drug ratios. Oncol Res 16(8):361–37410.3727/000000006783980937 ↗
45. He X, Zhang H, Ma Y, Bai W, Zhang Z, Lu K, Ding Y, Zhao Y, Chai Z (2010) Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation. Nanotechnology 21(28):285103. doi: 10.1088/0957-4484/21/28/28510310.1088/0957-4484/21/28/285103 ↗
46. He Q, Gao Y, Zhang L, Zhang Z, Gao F, Ji X, Li Y, Shi J (2011) A pH-responsive mesoporous silica nanoparticles-based multi-drug delivery system for overcoming multi-drug resistance. Biomaterials 32(30):7711–7720. doi: 10.1016/j.biomaterials.2011.06.06610.1016/j.biomaterials.2011.06.066 ↗
47. Herai H, Gratieri T, Thomazine JA, Bentley MV, Lopez RF (2007) Doxorubicin skin penetration from monoolein-containing propylene glycol formulations. Int J Pharm 329(1–2):88–93. doi: 10.1016/j.ijpharm.2006.08.02110.1016/j.ijpharm.2006.08.021 ↗
48. Hong H, Zhang Y, Sun J, Cai W (2009) Molecular imaging and therapy of cancer with radiolabeled nanoparticles. Nano today 4(5):399–413. doi: 10.1016/j.nantod.2009.07.00110.1016/j.nantod.2009.07.001 ↗
49. Hong C, Lee J, Zheng H, Hong SS, Lee C (2011) Porous silicon nanoparticles for cancer photothermotherapy. Nanoscale Res Lett 6(1):321. doi: 10.1186/1556-276X-6-32110.1186/1556-276X-6-321 ↗
50. Hu YL, Gao JQ (2010) Potential neurotoxicity of nanoparticles. Int J Pharm 394(1–2):115–121. doi: 10.1016/j.ijpharm.2010.04.026
51. Hu CM, Aryal S, Zhang L (2010) Nanoparticle-assisted combination therapies for effective cancer treatment. Ther Deliv 1(2):323–33410.4155/tde.10.13 ↗
52. Huang G, Zhang N, Bi X, Dou M (2008) Solid lipid nanoparticles of temozolomide: potential reduction of cardial and nephric toxicity. Int J Pharm 355(1–2):314–320. doi: 10.1016/j.ijpharm.2007.12.01310.1016/j.ijpharm.2007.12.013 ↗
53. Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomed 1(3):297–31510.2217/17435889.1.3.297 ↗
54. Jain PK, Huang X, El-Sayed IH, El-Sayed MA (2008) Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. Acc Chem Res 41(12):1578–1586. doi: 10.1021/ar700280410.1021/ar7002804 ↗
55. Jarrett BR, Gustafsson B, Kukis DL, Louie AY (2008) Synthesis of 64Cu-labeled magnetic nanoparticles for multimodal imaging. Bioconjug Chem 19(7):1496–1504. doi: 10.1021/bc800108v10.1021/bc800108v ↗
56. Johnston HJ, Semmler-Behnke M, Brown DM, Kreyling W, Tran L, Stone V (2010) Evaluating the uptake and intracellular fate of polystyrene nanoparticles by primary and hepatocyte cell lines in vitro. Toxicol Appl Pharmacol 242(1):66–78. doi: 10.1016/j.taap.2009.09.01510.1016/j.taap.2009.09.015 ↗
57. Jokerst JV, Lobovkina T, Zare RN, Gambhir SS (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond) 6(4):715–728. doi: 10.2217/nnm.11.1910.2217/nnm.11.19 ↗
58. Kadam RS, Bourne DW, Kompella UB (2012) Nano-advantage in enhanced drug delivery with biodegradable nanoparticles: contribution of reduced clearance. Drug Metab Dispos Biol Fate Chem 40(7):1380–1388. doi: 10.1124/dmd.112.04492510.1124/dmd.112.044925 ↗
59. Kamaly N, Xiao Z, Valencia PM, Radovic-Moreno AF, Farokhzad OC (2012) Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev 41(7):2971–3010. doi: 10.1039/c2cs15344k10.1039/c2cs15344k ↗
60. Kim DW, Kim SY, Kim HK, Kim SW, Shin SW, Kim JS, Park K, Lee MY, Heo DS (2007) Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer. Ann Oncol 18(12):2009–2014. doi: 10.1093/annonc/mdm37410.1093/annonc/mdm374 ↗
61. Koc K, Anik I, Cabuk B, Ceylan S (2008) Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. Br J Neurosurg 22(1):99–103. doi: 10.1080/0268869070176552410.1080/02688690701765524 ↗
62. Koo H, Huh MS, Sun IC, Yuk SH, Choi K, Kim K, Kwon IC (2011) In vivo targeted delivery of nanoparticles for theranosis. Acc Chem Res 44(10):1018–1028. doi: 10.1021/ar200013810.1021/ar2000138 ↗
63. Krishnan V, Xu X, Barwe SP, Yang X, Czymmek K, Waldman SA, Mason RW, Jia X, Rajasekaran AK (2013) Dexamethasone-loaded block copolymer nanoparticles induce leukemia cell death and enhance therapeutic efficacy: a novel application in pediatric nanomedicine. Mol Pharm 10(6):2199–2210. doi: 10.1021/mp300350e10.1021/mp300350e ↗
64. Kularatne SA, Low PS (2010) Targeting of nanoparticles: folate receptor. Methods Mol Biol 624:249–265. doi: 10.1007/978-1-60761-609-2_1710.1007/978-1-60761-609-2_17 ↗
65. Kurmi BD, Kayat J, Gajbhiye V, Tekade RK, Jain NK (2010) Micro- and nanocarrier-mediated lung targeting. Expert Opin Drug Deliv 7(7):781–794. doi: 10.1517/17425247.2010.49221210.1517/17425247.2010.492212 ↗
66. Kwatra SG, Tey HL, Ali SM, Dabade T, Chan YH, Yosipovitch G (2012) The infra-auricular fissure: a bedside marker of disease severity in patients with atopic dermatitis. J Am Acad Dermatol 66(6):1009–1010. doi: 10.1016/j.jaad.2011.10.03110.1016/j.jaad.2011.10.031 ↗
67. Lai SK, Wang YY, Hanes J (2009) Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61(2):158–171. doi: 10.1016/j.addr.2008.11.00210.1016/j.addr.2008.11.002 ↗
68. Li Z, Su K, Cheng B, Deng Y (2010) Organically modified MCM-type material preparation and its usage in controlled amoxicillin delivery. J Colloid Interface Sci 342(2):607–613. doi: 10.1016/j.jcis.2009.10.07310.1016/j.jcis.2009.10.073 ↗
69. Li R, Eun JS, Lee MK (2011a) Pharmacokinetics and biodistribution of paclitaxel loaded in pegylated solid lipid nanoparticles after intravenous administration. Arch Pharm Res 34(2):331–337. doi: 10.1007/s12272-011-0220-210.1007/s12272-011-0220-2 ↗
70. Li Y, Zhou Y, Wang HY, Perrett S, Zhao Y, Tang Z, Nie G (2011b) Chirality of glutathione surface coating affects the cytotoxicity of quantum dots. Angew Chem 50(26):5860–5864. doi: 10.1002/anie.20100820610.1002/anie.201008206 ↗
71. Liu X, Sun J (2010) Endothelial cells dysfunction induced by silica nanoparticles through oxidative stress via JNK/P53 and NF-kappaB pathways. Biomaterials 31(32):8198–8209. doi: 10.1016/j.biomaterials.2010.07.06910.1016/j.biomaterials.2010.07.069 ↗
72. Liu M, Zhang H, Slutsky AS (2009) Acute lung injury: a yellow card for engineered nanoparticles? J Mol Cell Biol 1(1):6–7. doi: 10.1093/jmcb/mjp00610.1093/jmcb/mjp006 ↗
73. Longmire M, Choyke PL, Kobayashi H (2008) Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. Nanomedicine (Lond) 3(5):703–717. doi: 10.2217/17435889.3.5.70310.2217/17435889.3.5.703 ↗
74. Lv Q, Yu A, Xi Y, Li H, Song Z, Cui J, Cao F, Zhai G (2009) Development and evaluation of penciclovir-loaded solid lipid nanoparticles for topical delivery. Int J Pharm 372(1–2):191–198. doi: 10.1016/j.ijpharm.2009.01.01410.1016/j.ijpharm.2009.01.014 ↗
75. Madani SY, Naderi N, Dissanayake O, Tan A, Seifalian AM (2011) A new era of cancer treatment: carbon nanotubes as drug delivery tools. Int J Nanomed 6:2963–2979. doi: 10.2147/ijn.s1692310.2147/IJN.S16923 ↗
76. Maeda H, Bharate GY, Daruwalla J (2009) Polymeric drugs for efficient tumor-targeted drug delivery based on EPR-effect. Eur J Pharm Biopharm 71(3):409–419. doi: 10.1016/j.ejpb.2008.11.01010.1016/j.ejpb.2008.11.010 ↗
77. Majoros IJ, Williams CR, Becker AC, Baker JR Jr (2009) Surface interaction and behavior of poly(amidoamine) dendrimers: deformability and lipid bilayer disruption. J Comput Theor Nanosci 6(7):1430–1436. doi: 10.1166/jctn.2009.118910.1166/jctn.2009.1189 ↗
78. Makadia HK, Siegel SJ (2011) Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 3(3):1377–1397. doi: 10.3390/polym303137710.3390/polym3031377 ↗
79. Mandal S, Bakeine GJ, Krol S, Ferrari C, Clerici AM, Zonta C, Cansolino L, Ballarini F, Bortolussi S, Stella S, Protti N, Bruschi P, Altieri S (2011) Design, development and characterization of multi-functionalized gold nanoparticles for biodetection and targeted boron delivery in BNCT applications. Appl Radiat Isot 69(12):1692–1697. doi: 10.1016/j.apradiso.2011.05.00210.1016/j.apradiso.2011.05.002 ↗
80. Masserini M (2013) Nanoparticles for brain drug delivery. ISRN Biochem 2013:1–18. doi: 10.1155/2013/23842810.1155/2013/238428 ↗
81. Medina C, Santos-Martinez MJ, Radomski A, Corrigan OI, Radomski MW (2007) Nanoparticles: pharmacological and toxicological significance. Br J Pharmacol 150(5):552–558. doi: 10.1038/sj.bjp.070713010.1038/sj.bjp.0707130 ↗
82. Merian J, Gravier J, Navarro F, Texier I (2012) Fluorescent nanoprobes dedicated to in vivo imaging: from preclinical validations to clinical translation. Molecules 17(5):5564–5591. doi: 10.3390/molecules1705556410.3390/molecules17055564 ↗
83. Mieog JS, Hutteman M, van der Vorst JR, Kuppen PJ, Que I, Dijkstra J, Kaijzel EL, Prins F, Lowik CW, Smit VT, van de Velde CJ, Vahrmeijer AL (2011) Image-guided tumor resection using real-time near-infrared fluorescence in a syngeneic rat model of primary breast cancer. Breast Cancer Res Treat 128(3):679–689. doi: 10.1007/s10549-010-1130-610.1007/s10549-010-1130-6 ↗
84. Montet X, Funovics M, Montet-Abou K, Weissleder R, Josephson L (2006) Multivalent effects of RGD peptides obtained by nanoparticle display. J Med Chem 49(20):6087–6093. doi: 10.1021/jm060515m10.1021/jm060515m ↗
85. Mortimer JE, Bading JR, Colcher DM, Conti PS, Frankel PH, Carroll MI, Tong S, Poku E, Miles JK, Shively JE, Raubitschek AA (2014) Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. J Nucl Med 55(1):23–29. doi: 10.2967/jnumed.113.12263010.2967/jnumed.113.122630 ↗
86. Mudshinge SR, Deore AB, Patil S, Bhalgat CM (2011) Nanoparticles: emerging carriers for drug delivery. Saudi Pharm J 19(3):129–141. doi: 10.1016/j.jsps.2011.04.00110.1016/j.jsps.2011.04.001 ↗
87. Murata M, Yonamine T, Tanaka S, Tahara K, Tozuka Y, Takeuchi H (2013) Surface modification of liposomes using polymer-wheat germ agglutinin conjugates to improve the absorption of peptide drugs by pulmonary administration. J Pharm Sci 102(4):1281–1289. doi: 10.1002/jps.2346310.1002/jps.23463 ↗
88. Muro S, Garnacho C, Champion JA, Leferovich J, Gajewski C, Schuchman EH, Mitragotri S, Muzykantov VR (2008) Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. Mol Ther 16(8):1450–1458. doi: 10.1038/mt.2008.12710.1038/mt.2008.127 ↗
89. Nair KL, Jagadeeshan S, Nair SA, Kumar GS (2011) Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA. Int J Nanomed 6:1685–1697. doi: 10.2147/IJN.S20165
90. Napierska D, Thomassen LC, Lison D, Martens JA, Hoet PH (2010) The nanosilica hazard: another variable entity. Part Fibre Toxicol 7(1):39. doi: 10.1186/1743-8977-7-3910.1186/1743-8977-7-39 ↗
91. Olivier JC (2005) Drug transport to brain with targeted nanoparticles. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 2(1):108–119. doi: 10.1602/neurorx.2.1.10810.1602/neurorx.2.1.108 ↗
92. Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307(1):93–102. doi: 10.1016/j.ijpharm.2005.10.01010.1016/j.ijpharm.2005.10.010 ↗
93. Paino IM, Marangoni VS, de Oliveira Rde C, Antunes LM, Zucolotto V (2012) Cyto and genotoxicity of gold nanoparticles in human hepatocellular carcinoma and peripheral blood mononuclear cells. Toxicol Lett 215(2):119–125. doi: 10.1016/j.toxlet.2012.09.02510.1016/j.toxlet.2012.09.025 ↗
94. Pan TL, Wang PW, Al-Suwayeh SA, Huang YJ, Fang JY (2012) Toxicological effects of cationic nanobubbles on the liver and kidneys: biomarkers for predicting the risk. Food Chem Toxicol 50(11):3892–3901. doi: 10.1016/j.fct.2012.07.00510.1016/j.fct.2012.07.005 ↗
95. Pandey R, Khuller GK (2005) Solid lipid particle-based inhalable sustained drug delivery system against experimental tuberculosis. Tuberculosis (Edinb) 85(4):227–234. doi: 10.1016/j.tube.2004.11.00310.1016/j.tube.2004.11.003 ↗
96. Paolino D, Muzzalupo R, Ricciardi A, Celia C, Picci N, Fresta M (2007) In vitro and in vivo evaluation of Bola-surfactant containing niosomes for transdermal delivery. Biomed Microdevices 9(4):421–433. doi: 10.1007/s10544-007-9046-610.1007/s10544-007-9046-6 ↗
97. Paolino D, Cosco D, Muzzalupo R, Trapasso E, Picci N, Fresta M (2008) Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer. Int J Pharm 353(1–2):233–242. doi: 10.1016/j.ijpharm.2007.11.03710.1016/j.ijpharm.2007.11.037 ↗
98. Park K (2012) Toxicity risk of nanocarriers. J Control Release 160(1):1–2. doi: 10.1016/j.jconrel.2012.05.01610.1016/j.jconrel.2012.05.016 ↗
99. Park JH, Lee S, Kim J-H, Park K, Kim K, Kwon IC (2008) Polymeric nanomedicine for cancer therapy. Prog Polym Sci 33(1):113–137. doi: 10.1016/j.progpolymsci.2007.09.00310.1016/j.progpolymsci.2007.09.003 ↗
100. Pavlov GM, Perevyazko IY, Okatova OV, Schubert US (2011) Conformation parameters of linear macromolecules from velocity sedimentation and other hydrodynamic methods. Methods 54(1):124–135. doi: 10.1016/j.ymeth.2011.02.00510.1016/j.ymeth.2011.02.005 ↗