Abstract
Breast cancer is the field of medicine with the greatest presence of nanotechnological therapeutic agents in the clinic. A pegylated form of liposomally encapsulated doxorubicin is routinely used for treatment against metastatic cancer, and albumin nanoparticulate chaperones of paclitaxel were approved for locally recurrent and metastatic disease in 2005. These drugs have yielded substantial clinical benefit, and are steadily gathering greater beneficial impact. Clinical trials currently employing these drugs in combination with chemo and biological therapeutics exceed 150 worldwide. Despite these advancements, breast cancer morbidity and mortality is unacceptably high. Nanotechnology offers potential solutions to the historical challenge that has rendered breast cancer so difficult to contain and eradicate: the extreme biological diversity of the disease presentation in the patient population and in the evolutionary changes of any individual disease, the multiple pathways that drive disease progression, the onset of ‘resistance’ to established therapeutic cocktails, and the gravity of the side effects to treatment, which result from generally very poor distribution of the injected therapeutic agents in the body. A fundamental requirement for success in the development of new therapeutic strategies is that breast cancer specialists—in the clinic, the pharmaceutical and the basic biological laboratory—and nanotechnologists—engineers, physicists, chemists and mathematicians—optimize their ability to work in close collaboration. This further requires a mutual openness across cultural and language barriers, academic reward systems, and many other ‘environmental’ divides. This paper is respectfully submitted to the community to help foster the mutual interactions of the breast cancer world with micro- and nano-technology, and in particular to encourage the latter community to direct ever increasing attention to breast cancer, where an extraordinary beneficial impact may result. The paper initiates with an introductory overview of breast cancer, its current treatment modalities, and the current role of nanotechnology in the clinic. Our perspectives are then presented on what the greatest opportunities for nanotechnology are; this follows from an analysis of the role of biological barriers that adversely determine the biological distribution of intravascularly injected therapeutic agents. Different generations of nanotechnology tools for drug delivery are reviewed, and our current strategy for addressing the sequential bio-barriers is also presented, and is accompanied by an encouragement to the community to develop even more effective ones.
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References
M.S. Aapro, Adjuvant therapy of primary breast cancer: a review of key findings from the 7th international conference, St. Gallen, February 2001 Oncologist 6, 376–385 (2001) doi:10.1634/theoncologist.6-4-376
M. Azemar, S. Djahansouzi, E. Jager, C. Solbach, M. Schmidt, A.B. Maurer et al., Regression of cutaneous tumor lesions in patients intratumorally injected with a recombinant single-chain antibody-toxin targeted to ErbB2/HER2 Breast Cancer Res. Treat. 82, 155–164 (2003) doi:10.1023/B:BREA.0000004371.48757.19
D.C. Bibby, J.E. Talmadge, M.K. Dalal, S.G. Kurz, K.M. Chytil, S.E. Barry et al., Pharmacokinetics and biodistribution of RGD-targeted doxorubicin-loaded nanoparticles in tumor-bearing mice Int. J. Pharm. 293, 281–290 (2005) doi:10.1016/j.ijpharm.2004.12.021
N. Bogdanova, S. Feshchenko, C. Cybulski, T. Dork, CHEK2 mutation and hereditary breast cancer J. Clin. Oncol. 25, e26 (2007) doi:10.1200/JCO.2007.11.4223
Y. Boucher, L.T. Baxter, R.K. Jain, Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy Cancer Res. 50, 4478–4484 (1990)
Y. Boucher, J.M. Kirkwood, D. Opacic, M. Desantis, R.K. Jain, Interstitial hypertension in superficial metastatic melanomas in humans Cancer Res. 51, 6691–6694 (1991)
P. Buchler, H.A. Reber, M.M. Roth, M. Shiroishi, H. Friess, O.J. Hines, Target therapy using a small molecule inhibitor against angiogenic receptors in pancreatic cancer Neoplasia 9, 119–127 (2007) doi:10.1593/neo.06616
L.A. Carey, E.C. Dees, L. Sawyer, L. Gatti, D.T. Moore, F. Collichio et al., The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes Clin. Cancer Res. 13, 2329–2334 (2007) doi:10.1158/1078-0432.CCR-06-1109
S. Cleator, W. Heller, R.C. Coombes, Triple-negative breast cancer: therapeutic options Lancet Oncol. 8, 235–244 (2007) doi:10.1016/S1470-2045(07)70074-8
M.J. Cloninger, Biological applications of dendrimers Curr. Opin. Chem. Biol. 6, 742–748 (2002) doi:10.1016/S1367-5931(02)00400-3
M.A. Cobleigh, C.L. Vogel, D. Tripathy, N.J. Robert, S. Scholl, L. Fehrenbacher et al., Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease J. Clin. Oncol. 17, 2639–2648 (1999)
J. Cuzick, T. Powles, U. Veronesi, J. Forbes, R. Edwards, S. Ashley et al., Overview of the main outcomes in breast-cancer prevention trials Lancet 361, 296–300 (2003) doi:10.1016/S0140-6736(03)12342-2
A.M. Davidoff, P.A. Humphrey, J.D. Iglehart, J.R. Marks, Genetic basis for p53 overexpression in human breast cancer Proc. Natl. Acad. Sci. USA 88, 5006–5010 (1991) doi:10.1073/pnas.88.11.5006
P. Decuzzi, M. Ferrari, The adhesive strength of non-spherical particles mediated by specific interactions Biomaterials 27, 5307–5314 (2006) doi:10.1016/j.biomaterials.2006.05.024
P. Decuzzi, M. Ferrari, Design maps for nanoparticles targeting the diseased microvasculature Biomaterials 29, 377–384 (2008)
P. Decuzzi, S. Lee, B. Bhushan, M. Ferrari, A theoretical model for the margination of particles within blood vessels Ann. Biomed. Eng. 33, 179–190 (2005) doi:10.1007/s10439-005-8976-5
P. Decuzzi, R. Pasqualini, W. Arap, M. Ferrari, Intravascular delivery of particulate systems: Does geometry really matter? Pharm. Res. (2008) Accepted
A. Di Paolo, Liposomal anticancer therapy: pharmacokinetic and clinical aspects J. Chemother. 16(Suppl 4), 90–93 (2004)
R. Duncan, The dawning era of polymer therapeutics Nat. Rev. Drug Discov. 2, 347–360 (2003) doi:10.1038/nrd1088
Early Breast Cancer Trialists’ Collaborative Group, Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials Lancet 365, 1687–1717 (2005) doi:10.1016/S0140-6736(05)66544-0
J.M. Elwood, B. Cox, A.K. Richardson, The effectiveness of breast cancer screening by mammography in younger women. Online J. Curr. Clin. Trials Doc No 32:[23,227 words; 195 paragraphs] (1993)
O.C. Farokhzad, J. Cheng, B.A. Teply, I. Sherifi, S. Jon, P.W. Kantoff et al., Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo Proc. Natl. Acad. Sci. USA 103, 6315–6320 (2006a) doi:10.1073/pnas.0601755103
O.C. Farokhzad, J.M. Karp, R. Langer, Nanoparticle-aptamer bioconjugates for cancer targeting Expert Opin. Drug Deliv. 3, 311–324 (2006b) doi:10.1517/17425247.3.3.311
B.M. Fendly, M. Winget, R.M. Hudziak, M.T. Lipari, M.A. Napier, A. Ullrich, Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product Cancer Res. 50, 1550–1558 (1990)
M. Ferrari, Cancer nanotechnology: opportunities and challenges Nat. Rev. Cancer 5, 161–171 (2005a) doi:10.1038/nrc1566
M. Ferrari, Nanovector therapeutics Curr. Opin. Chem. Biol. 9, 343–346 (2005b) doi:10.1016/j.cbpa.2005.06.001
M. Ferrari, Beyond drug delivery Nat. Nanotechnol. 3, 131–132 (2008a) doi:10.1038/nnano.2008.46
M. Ferrari, Cancer Nanotechnology, in Cancer Medicine e.8, ed. by R. Bast, E. Frei, J.F. Holland, et al. (BC Decker Inc.), (2008b) (in press)
B. Fisher, J.P. Costantino, D.L. Wickerham, R.S. Cecchini, W.M. Cronin, A. Robidoux et al., Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study J. Natl. Cancer Inst. 97, 1652–1662 (2005)
F.A. Fornari, J.K. Randolph, J.C. Yalowich, M.K. Ritke, D.A. Gewirtz, Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells Mol. Pharmacol. 45, 649–656 (1994)
T. Fujita, A scanning electron microscope study of the human spleen Arch. Histol. Jpn. 37, 187–216 (1974)
A. Gabizon, H. Shmeeda, A.T. Horowitz, S. Zalipsky, Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates Adv. Drug Deliv. Rev. 56, 1177–1192 (2004) doi:10.1016/j.addr.2004.01.011
F. Gentile, M. Ferrari, P. Decuzzi, The transport of nanoparticles in blood vessels: the effect of vessel permeability and blood rheology Ann. Biomed. Eng. 36, 254–261 (2008) doi:10.1007/s10439-007-9423-6
A.M. Gobin, M.H. Lee, N.J. Halas, W.D. James, R.A. Drezek, J.L. West, Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy Nano Lett. 7, 1929–1934 (2007) doi:10.1021/nl070610y
S. Green, P. Walter, V. Kumar, A. Krust, J.M. Bornert, P. Argos et al., Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A Nature 320, 134–139 (1986) doi:10.1038/320134a0
J.J. Green, E. Chiu, E.S. Leshchiner, J. Shi, R. Langer, D.G. Anderson, Electrostatic ligand coatings of nanoparticles enable ligand-specific gene delivery to human primary cells Nano Lett. 7, 874–879 (2007) doi:10.1021/nl062395b
H. Hashizume, P. Baluk, S. Morikawa, J.W. McLean, G. Thurston, S. Roberge et al., Openings between defective endothelial cells explain tumor vessel leakiness Am. J. Pathol. 156, 1363–1380 (2000)
C.H. Heldin, K. Rubin, K. Pietras, A. Ostman, High interstitial fluid pressure—an obstacle in cancer therapy Nat. Rev. Cancer 4, 806–813 (2004) doi:10.1038/nrc1456
P. Henneke, D.T. Golenbock, Phagocytosis, innate immunity, and host-pathogen specificity J. Exp. Med. 199, 1–4 (2004) doi:10.1084/jem.20031256
L.R. Hirsch, R.J. Stafford, J.A. Bankson, S.R. Sershen, B. Rivera, R.E. Price et al., Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance Proc. Natl. Acad. Sci. USA 100, 13549–13554 (2003) doi:10.1073/pnas.2232479100
G.N. Hortobagyi, Anthracyclines in the treatment of cancer. An overview Drugs 54(Suppl 4), 1–7 (1997) doi:10.2165/00003495-199754010-00001
L. Illum, S.S. Davis, The targeting of drugs parenterally by use of microspheres J. Parenter. Sci. Technol. 36, 242–248 (1982)
M. Infanger, M. Shakibaei, P. Kossmehl, S.M. Hollenberg, J. Grosse, S. Faramarzi et al., Intraluminal application of vascular endothelial growth factor enhances healing of microvascular anastomosis in a rat model J. Vasc. Res. 42, 202–213 (2005) doi:10.1159/000085176
R.K. Jain, Molecular regulation of vessel maturation Nat. Med. 9, 685–693 (2003) doi:10.1038/nm0603-685
A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, M.J. Thun, Cancer statistics, 2007 CA Cancer J. Clin. 57, 43–66 (2007)
N.W. Kam, M. O'Connell, J.A. Wisdom, H. Dai, Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction Proc. Natl. Acad. Sci. USA 102, 11600–11605 (2005) doi:10.1073/pnas.0502680102
M.W. Kanan, T.J. Ryan, A.G. Weddell, The behaviour of the nasal mucosa towards blood borne colloidal carbon in experimental animals Pathol. Eur. 10, 263–276 (1975)
M. Karon, S. Weissman, C. Meyer, P. Henry, Studies of DNA, Rna, and Protein Synthesis in Cultured Human Cells Exposed to 8-Azaguanine Cancer Res. 25, 185–192 (1965)
K Kerlikowske, Efficacy of screening mammography among women aged 40 to 49 years and 50 to 69 years: comparison of relative and absolute benefit J. Natl. Cancer Inst. Monogr. 22, 79–86 (1997)
L.A. Khawli, G.K. Miller, A.L. Epstein, Effect of seven new vasoactive immunoconjugates on the enhancement of monoclonal antibody uptake in tumors Cancer 73, 824–831 (1994) doi:10.1002/1097-0142(19940201)73:3+<824::AID-CNCR2820731312>3.0.CO;2-V
G. Konecny, G. Pauletti, M. Pegram, M. Untch, S. Dandekar, Z. Aguilar et al., Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer J. Natl. Cancer Inst. 95, 142–153 (2003)
N. Kumar, Taxol-induced polymerization of purified tubulin. Mechanism of action J. Biol. Chem. 256, 10435–10441 (1981)
V. Kumar, S. Green, A. Staub, P. Chambon, Localisation of the oestradiol-binding and putative DNA-binding domains of the human oestrogen receptor EMBO J. 5, 2231–2236 (1986)
V. Kumar, S. Green, G. Stack, M. Berry, J.R. Jin, P. Chambon, Functional domains of the human estrogen receptor Cell 51, 941–951 (1987) doi:10.1016/0092-8674(87)90581-2
J.R. Less, T.C. Skalak, E.M. Sevick, R.K. Jain, Microvascular architecture in a mammary carcinoma: branching patterns and vessel dimensions Cancer Res. 51, 265–273 (1991)
J.R. Less, M.C. Posner, Y. Boucher, D. Borochovitz, N. Wolmark, R.K. Jain, Interstitial hypertension in human breast and colorectal tumors Cancer Res. 52, 6371–6374 (1992a)
J.R. Less, T.C. Skalak, E.M. Sevick, R.K. Jain, Microvascular network architecture in a mammary carcinoma EXS 61, 74–80 (1992b)
J. Li, C. Yen, D. Liaw, K. Podsypanina, S. Bose, S.I. Wang et al., PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer Science 275, 1943–1947 (1997) doi:10.1126/science.275.5308.1943
J. Liebmann, J.A. Cook, J.B. Mitchell, Cremophor EL, solvent for paclitaxel, and toxicity Lancet 342, 1428 (1993) doi:10.1016/0140-6736(93)92789-V
C. Loo, A. Lowery, N. Halas, J. West, R. Drezek, Immunotargeted nanoshells for integrated cancer imaging and therapy Nano Lett. 5, 709–711 (2005) doi:10.1021/nl050127s
H. Maeda, The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting Adv. Enzyme Regul. 41, 189–207 (2001) doi:10.1016/S0065-2571(00)00013-3
H. Maeda, J. Fang, T. Inutsuka, Y. Kitamoto, Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications Int. Immunopharmacol. 3, 319–328 (2003) doi:10.1016/S1567-5769(02)00271-0
F.J. Martin, K. Melnik, T. West, J. Shapiro, M. Cohen, A.A. Boiarski et al., Acute toxicity of intravenously administered microfabricated silicon dioxide drug delivery particles in mice: preliminary findings Drugs R D. 6, 71–81 (2005) doi:10.2165/00126839-200506020-00002
T. Murakami, T. Fujita, M. Miyoshi, Closed circulation in the rat spleen as evidenced by scanning electron microscopy of vascular casts Experientia 29, 1374–1375 (1973) doi:10.1007/BF01922828
T. Thei, D. Peter, J.K. Eric Drexler et al., Nan’o.tech.nol’o.gy n. Nat. Nanotechnol. 1, 8–10 (2006) doi 10.1038/nnano.2006.77
S.D. Nathanson, L. Nelson, Interstitial fluid pressure in breast cancer, benign breast conditions, and breast parenchyma Ann. Surg. Oncol. 1, 333–338 (1994)
D. Neri, R. Bicknell, Tumour vascular targeting Nat. Rev. Cancer 5, 436–446 (2005) doi:10.1038/nrc1627
D.W. Nyman, K.J. Campbell, E. Hersh, K. Long, K. Richardson, V. Trieu et al., Phase I and pharmacokinetics trial of ABI-007, a novel nanoparticle formulation of paclitaxel in patients with advanced nonhematologic malignancies J. Clin. Oncol. 23, 7785–7793 (2005) doi:10.1200/JCO.2004.00.6148
M.O. Oyewumi, R.J. Mumper, Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy Bioconjug. Chem. 13, 1328–1335 (2002) doi:10.1021/bc025560x
B. Pan, D. Cui, Y. Sheng, C. Ozkan, F. Gao, R. He et al., Dendrimer-Modified Magnetic Nanoparticles Enhance Efficiency of Gene Delivery System Cancer Res. 67, 8156–8163 (2007) doi:10.1158/0008-5472.CAN-06-4762
D.M. Parkin, Global cancer statistics in the year 2000 Lancet Oncol. 2, 533–543 (2001) doi:10.1016/S1470-2045(01)00486-7
R. Pasqualini, E. Koivunen, E. Ruoslahti, Alpha v integrins as receptors for tumor targeting by circulating ligands Nat. Biotechnol. 15, 542–546 (1997) doi:10.1038/nbt0697-542
J. Peng, X. He, K. Wang, W. Tan, H. Li, X. Xing et al., An antisense oligonucleotide carrier based on amino silica nanoparticles for antisense inhibition of cancer cells Nanomedicine 2, 113–120 (2006)
C.M. Perou, T. Sorlie, M.B. Eisen, M. van de Rijn, S.S. Jeffrey, C.A. Rees et al., Molecular portraits of human breast tumours Nature 406, 747–752 (2000) doi:10.1038/35021093
Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 352, 930–942 (1998) doi:10.1016/S0140-6736(98)03301-7
G.S. Rao, MOde of entry of steroid and thyroid hormones into cells Mol. Cell. Endocrinol. 21, 97–108 (1981) doi:10.1016/0303-7207(81)90047-2
R.P. Rapp, B.A. Bivins, Final in-line filtration: removal of contaminants from IV fluids and drugs Hosp. Formul. 18, 1124–1128 (1983)
E. Rivera, Liposomal anthracyclines in metastatic breast cancer: clinical update Oncologist 8(Suppl 2), 3–9 (2003) doi:10.1634/theoncologist.8-suppl_2–3
H.D. Roh, Y. Boucher, S. Kalnicki, R. Buchsbaum, W.D. Bloomer, R.K. Jain, Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response Cancer Res. 51, 6695–6698 (1991)
W.R. Sanhai, J.H. Sakamoto, R. Canady, M. Ferrari, Seven challenges for nanomedicine Nat. Nanotechnol. 3, 242–244 (2008) doi:10.1038/nnano.2008.114
V. Sharifi-Salamatian, B. Pesquet-Popescu, J. Simony-Lafontaine, J.P. Rigaut, Index for spatial heterogeneity in breast cancer J. Microsc. 216, 110–122 (2004) doi:10.1111/j.0022-2720.2004.01398.x
D. Simberg, T. Duza, J.H. Park, M. Essler, J. Pilch, L. Zhang et al., Biomimetic amplification of nanoparticle homing to tumors Proc. Natl. Acad. Sci. USA 104, 932–936 (2007) doi:10.1073/pnas.0610298104
D.J. Slamon, G.M. Clark, S.G. Wong, W.J. Levin, A. Ullrich, W.L. McGuire, Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene Science 235, 177–182 (1987) doi:10.1126/science.3798106
D.J. Slamon, W. Godolphin, L.A. Jones, J.A. Holt, S.G. Wong, D.E. Keith et al., Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer Science 244, 707–712 (1989) doi:10.1126/science.2470152
D.J. Slamon, B. Leyland-Jones, S. Shak, H. Fuchs, V. Paton, A. Bajamonde et al., Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 N. Engl. J. Med. 344, 783–792 (2001) doi:10.1056/NEJM200103153441101
E.L. Snyder, C.C. Saenz, C. Denicourt, B.R. Meade, X.S. Cui, I.M. Kaplan et al., Enhanced targeting and killing of tumor cells expressing the CXC chemokine receptor 4 by transducible anticancer peptides Cancer Res. 65, 10646–10650 (2005) doi:10.1158/0008-5472.CAN-05-0118
I. Steinhauser, B. Spankuch, K. Strebhardt, K. Langer, Trastuzumab-modified nanoparticles: optimisation of preparation and uptake in cancer cells Biomaterials 27, 4975–4983 (2006) doi:10.1016/j.biomaterials.2006.05.016
M. Stohrer, Y. Boucher, M. Stangassinger, R.K. Jain, Oncotic pressure in solid tumors is elevated Cancer Res. 60, 4251–4255 (2000)
A.G. Taghian, R. Abi-Raad, S.I. Assaad, A. Casty, M. Ancukiewicz, E. Yeh et al., Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications J. Clin. Oncol. 23, 1951–1961 (2005) doi:10.1200/JCO.2005.08.119
A. Takeda, T. Miyoshi, H. Shimada, T. Ochiai, K. Isono, Enhanced effects of monoclonal antibody carboplatin immunoconjugates uptake and anti-tumor effects with angiotensin II and tumor necrosis factor J. Chemother. 11, 137–143 (1999)
E. Tasciotti, X.W. Liu, R. Bhavane, K. Plant, A.D. Leonard, B.K. Price et al., Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications Nat. Nanotechnol. 3, 151–157 (2008) doi:10.1038/nnano.2008.34
K. Umesono, R.M. Evans, Determinants of target gene specificity for steroid/thyroid hormone receptors Cell 57, 1139–1146 (1989) doi:10.1016/0092-8674(89)90051-2
D.D. Von Hoff, M.W. Layard, P. Basa, H.L. Davis Jr., A.L. Von Hoff, M. Rozencweig et al., Risk factors for doxorubicin-induced congestive heart failure Ann. Intern. Med. 91, 710–717 (1979)
P.L. Welcsh, M.C. King, BRCA1 and BRCA2 and the genetics of breast and ovarian cancer Hum. Mol. Genet. 10, 705–713 (2001) doi:10.1093/hmg/10.7.705
E. Wisse, F. Braet, D. Luo, R. De Zanger, D. Jans, E. Crabbe et al., Structure and function of sinusoidal lining cells in the liver Toxicol. Pathol. 24, 100–111 (1996)
L. Witte, D.J. Hicklin, Z. Zhu, B. Pytowski, H. Kotanides, P. Rockwell et al., Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an anti-angiogenic therapeutic strategy Cancer Metastasis Rev. 17, 155–161 (1998) doi:10.1023/A:1006094117427
J. Wu, T. Akaike, K. Hayashida, T. Okamoto, A. Okuyama, H. Maeda, Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinases Jpn. J. Cancer Res. 92, 439–451 (2001)
F. Yan, R. Kopelman, The embedding of meta-tetra(hydroxyphenyl)-chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties Photochem. Photobiol. 78, 587–591 (2003) doi:10.1562/0031-8655(2003)078<0587:TEOMIS>2.0.CO;2
F. Yan, H. Xu, J. Anker, R. Kopelman, B. Ross, A. Rehemtulla et al., Synthesis and characterization of silica-embedded iron oxide nanoparticles for magnetic resonance imaging J. Nanosci. Nanotechnol. 4, 72–76 (2004) doi:10.1166/jnn.2004.074
X. Yang, H. Wang, D.W. Beasley, D.E. Volk, X. Zhao, B.A. Luxon et al., Selection of thioaptamers for diagnostics and therapeutics Ann. N. Y. Acad. Sci. 1082, 116–119 (2006) doi:10.1196/annals.1348.065
Y. Yarden, M.X. Sliwkowski, Untangling the ErbB signalling network Nat. Rev. Mol. Cell Biol. 2, 127–137 (2001) doi:10.1038/35052073
K.T. Yong, J. Qian, I. Roy, H.H. Lee, E.J. Bergey, K.M. Tramposch et al., Quantum rod bioconjugates as targeted probes for confocal and two-photon fluorescence imaging of cancer cells Nano Lett. 7, 761–765 (2007) doi:10.1021/nl063031m
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Tanaka, T., Decuzzi, P., Cristofanilli, M. et al. Nanotechnology for breast cancer therapy. Biomed Microdevices 11, 49–63 (2009). https://doi.org/10.1007/s10544-008-9209-0
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DOI: https://doi.org/10.1007/s10544-008-9209-0