Targeted drug delivery for tumor therapy inside the bone marrow

Martinez-Agosto, 2007, The hematopoietic stem cell and its niche: a comparative view, Gene. Dev., 21, 3044, 10.1101/gad.1602607 Le Blanc, 2012, Multipotent mesenchymal stromal cells and the innate immune system, Nat. Rev. Immunol., 12, 383, 10.1038/nri3209 Colmone, 2008, Leukemic cells create bone marrow niches that disrupt the behavior of normal hematopoietic progenitor cells, Science, 322, 1861, 10.1126/science.1164390 Podar, 2009, Bone marrow microenvironment and the identification of new targets for myeloma therapy, Leukemia, 23, 10, 10.1038/leu.2008.259 Suva, 2011, Bone metastasis: mechanisms and therapeutic opportunities, Nat. Rev. Endocrinol., 7, 208, 10.1038/nrendo.2010.227 Djunic, 2011, Osteolytic lesions marker in multiple myeloma, Med. Oncol., 28, 237, 10.1007/s12032-010-9432-4 Swami, 2014, Engineered nanomedicine for myeloma and bone microenvironment targeting, Proc. Natl. Acad. Sci. U. S. A., 111, 10287, 10.1073/pnas.1401337111 Adjei, 2016, Inhibition of bone loss with surface-modulated, drug-loaded nanoparticles in an intraosseous model of prostate cancer, J. Control Release, 232, 83, 10.1016/j.jconrel.2016.04.019 Sou, 2011, Bone marrow-targeted liposomal carriers, Expert Opin. Drug Deliv., 8, 317, 10.1517/17425247.2011.553218 Ewalt, 2016, Selective quantitation of microvessel density reveals sinusoidal expansion in myelodysplastic syndromes, Leuk. Lymphoma, 57, 2923, 10.3109/10428194.2016.1170829 Bianco, 2011, Bone and the hematopoietic niche: a tale of two stem cells, Blood, 117, 5281, 10.1182/blood-2011-01-315069 Morrison, 2014, The bone marrow niche for haematopoietic stem cells, Nature, 505, 327, 10.1038/nature12984 Nombela-Arrieta, 2013, Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment, Nat. Cell Biol., 15, 533, 10.1038/ncb2730 Vega, 2002, The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours, Br. J. Haematol., 117, 569, 10.1046/j.1365-2141.2002.03497.x Morrison, 2008, Stem cells and niches: mechanisms that promote stem cell maintenance throughout life, Cell., 132, 598, 10.1016/j.cell.2008.01.038 Moghimi, 1995, Exploiting bone marrow microvascular structure for drug delivery and future therapies, Adv. Drug Deliv. Rev., 17, 61, 10.1016/0169-409X(95)00041-5 Podar, 2005, The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications, Blood, 105, 1383, 10.1182/blood-2004-07-2909 Zhao, 2016, Endothelial progenitor cells promote tumor growth and progression by enhancing new vessel formation, Oncol. Lett., 12, 793, 10.3892/ol.2016.4733 Stasi, 2002, The role of angiogenesis in hematologic malignancies, J. Hematother. Stem Cell Res., 11, 49, 10.1089/152581602753448531 Negaard, 2009, Increased bone marrow microvascular density in haematological malignancies is associated with differential regulation of angiogenic factors, Leukemia, 23, 162, 10.1038/leu.2008.255 Chand, 2016, Role of microvessel density and vascular endothelial growth factor in angiogenesis of hematological malignancies, Bone Marrow Res., 2016, 10.1155/2016/5043483 Manier, 2012, Bone marrow microenvironment in multiple myeloma progression, J. Biomed. Biotechnol., 2012 Kiel, 2008, Uncertainty in the niches that maintain haematopoietic stem cells, Nat. Rev. Immunol., 8, 290, 10.1038/nri2279 Kaplan, 2005, VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche, Nature, 438, 820, 10.1038/nature04186 Chen, 2016, Fate decision of mesenchymal stem cells: adipocytes or osteoblasts[quest], Cell Death Differ., 23, 1128, 10.1038/cdd.2015.168 Boyle, 2003, Osteoclast differentiation and activation, Nature, 423, 337, 10.1038/nature01658 Ara, 2010, Interleukin-6 in bone metastasis and cancer progression, Eur. J. Cancer, 46, 1223, 10.1016/j.ejca.2010.02.026 Williams, 2006, Leukaemia: niche retreats for stem cells, Nature, 444, 827, 10.1038/444827a Kyle, 2009, Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma, Leukemia, 23, 3, 10.1038/leu.2008.291 Bataille, 1997, Multiple myeloma, N. Engl. J. Med., 336, 1657, 10.1056/NEJM199706053362307 Morgan, 2012, The genetic architecture of multiple myeloma, Nat. Rev. Cancer, 12, 335, 10.1038/nrc3257 Alsayed, 2007, Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma, Blood, 109, 2708, 10.1182/blood-2006-07-035857 Wang, 2007, Inhibition of adhesive interaction between multiple myeloma and bone marrow stromal cells by PPARgamma cross talk with NF-kappaB and C/EBP, Blood, 110, 4373, 10.1182/blood-2006-07-038026 Gupta, 2001, Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications, Leukemia, 15, 1950, 10.1038/sj.leu.2402295 Rajkumar, 2011, Treatment of multiple myeloma, Nat. Rev. Clin. Oncol., 8, 479, 10.1038/nrclinonc.2011.63 Lowenberg, 1999, Acute myeloid leukemia, N. Engl. J. Med., 341, 1051, 10.1056/NEJM199909303411407 Gray, 2010, Gastrointestinal complications in children with acute myeloid leukemia, Leuk. Lymphoma, 51, 768, 10.3109/10428191003695652 Li, 2014, High-dose cytarabine in acute myeloid leukemia treatment: a systematic review and meta-analysis, PLoS One, 9 Dombret, 2016, An update of current treatments for adult acute myeloid leukemia, Blood, 127, 53, 10.1182/blood-2015-08-604520 Coombs, 2016, Molecular therapy for acute myeloid leukaemia, Nat. Rev. Clin. Oncol., 13, 305, 10.1038/nrclinonc.2015.210 Schuch, 2002, In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo, Blood, 100, 4622, 10.1182/blood.V100.13.4622 Padro, 2000, Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia, Blood, 95, 2637, 10.1182/blood.V95.8.2637 Rodriguez-Ariza, 2011, VEGF targeted therapy in acute myeloid leukemia, Crit. Rev. Oncol. Hematol., 80, 241, 10.1016/j.critrevonc.2010.09.009 Lane, 2009, The leukemic stem cell niche: current concepts and therapeutic opportunities, Blood, 114, 1150, 10.1182/blood-2009-01-202606 Rashidi, 2015, Targeting the microenvironment in acute myeloid leukemia, Curr. Hematol. Malig. Rep., 10, 126, 10.1007/s11899-015-0255-4 Daley, 1990, Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome, Science, 247, 824, 10.1126/science.2406902 Zhang, 2013, Microenvironmental protection of CML stem and progenitor cells from tyrosine kinase inhibitors through N-cadherin and Wnt-beta-catenin signaling, Blood, 121, 1824, 10.1182/blood-2012-02-412890 Hantschel, 2012, BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia, Nat. Chem. Biol., 8, 285, 10.1038/nchembio.775 Corbin, 2011, Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity, J. Clin. Invest., 121, 396, 10.1172/JCI35721 Chu, 2011, Persistence of leukemia stem cells in chronic myelogenous leukemia patients in prolonged remission with imatinib treatment, Blood, 118, 5565, 10.1182/blood-2010-12-327437 Traer, 2012, Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors, Leukemia, 26, 1140, 10.1038/leu.2011.325 Matsunaga, 2003, Interaction between leukemic-cell VLA-4 and stromal fibronectin is a decisive factor for minimal residual disease of acute myelogenous leukemia, Nat. Med., 9, 1158, 10.1038/nm909 Zhang, 2007, Increased resistance to a farnesyltransferase inhibitor by N-cadherin expression in Bcr/Abl-P190 lymphoblastic leukemia cells, Leukemia, 21, 1189, 10.1038/sj.leu.2404667 Moslehi, 2015, Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia, J. Clin. Oncol., 33, 4210, 10.1200/JCO.2015.62.4718 Dahlen, 2016, Cardiovascular events associated with use of tyrosine kinase inhibitors in chronic myeloid leukemia: a population-based cohort study, Ann. Intern Med., 165, 161, 10.7326/M15-2306 Valent, 2015, Vascular safety issues in CML patients treated with BCR/ABL1 kinase inhibitors, Blood, 125, 901, 10.1182/blood-2014-09-594432 Mu, 2017, Codelivery of ponatinib and SAR302503 by active bone-targeted polymeric micelles for the treatment of therapy-resistant chronic myeloid leukemia, Mol. Pharm., 14, 274, 10.1021/acs.molpharmaceut.6b00872 Kuchuk, 2013, Incidence and consequences of bone metastases in lung cancer patients, J. Bone Oncol., 2, 22, 10.1016/j.jbo.2012.12.004 Croucher, 2016, Bone metastasis: the importance of the neighbourhood, Nat. Rev. Cancer, 16, 373, 10.1038/nrc.2016.44 Cohen, 2015, Inflammation mediated metastasis: immune induced epithelial-to-mesenchymal transition in inflammatory breast cancer cells, PLoS One, 10, 10.1371/journal.pone.0132710 Yu, 2014, Revisiting STAT3 signalling in cancer: new and unexpected biological functions, Nat. Rev. Cancer, 14, 736, 10.1038/nrc3818 Chang, 2013, The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis, Neoplasia, 15, 848, 10.1593/neo.13706 Rodriguez-Barrueco, 2015, Inhibition of the autocrine IL-6-JAK2-STAT3-calprotectin axis as targeted therapy for HR-/HER2+ breast cancers, Gene. Dev., 29, 1631, 10.1101/gad.262642.115 Jiang, 2014, Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications, Int. J. Pharm., 475, 547, 10.1016/j.ijpharm.2014.08.067 Jansen, 2010, Targeted radiotherapy of bone malignancies, Curr. Drug Discov. Technol., 7, 233, 10.2174/157016310793360675 Sou, 2007, Selective uptake of surface-modified phospholipid vesicles by bone marrow macrophages in vivo, Biomaterials, 28, 2655, 10.1016/j.biomaterials.2007.01.041 Sou, 2010, Bone marrow-targeted liposomal carriers: a feasibility study in nonhuman primates, Nanomed. (Lond), 5, 41, 10.2217/nnm.09.78 Tardi, 2009, In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy, Leuk. Res., 33, 129, 10.1016/j.leukres.2008.06.028 Tardi, 2016, Passive and semi-active targeting of bone marrow and leukemia cells using anionic low cholesterol liposomes, J. Drug Target, 24, 797, 10.1080/1061186X.2016.1184669 Zhang, 2012, A delivery system targeting bone formation surfaces to facilitate RNAi-based anabolic therapy, Nat. Med., 18, 307, 10.1038/nm.2617 Miller, 2011, Antiangiogenic antitumor activity of HPMA copolymer-paclitaxel-alendronate conjugate on breast cancer bone metastasis mouse model, Mol. Pharm., 8, 1052, 10.1021/mp200083n Gutbrodt, 2013, Antibody-based delivery of interleukin-2 to neovasculature has potent activity against acute myeloid leukemia, Sci. Transl. Med., 5, 10.1126/scitranslmed.3006221 Mai, 2014, Bone marrow endothelium-targeted therapeutics for metastatic breast cancer, J. Control Release, 187, 22, 10.1016/j.jconrel.2014.04.057 Zong, 2016, In vivo targeting of leukemia stem cells by directing parthenolide-loaded nanoparticles to the bone marrow niche, Leukemia, 30, 1582, 10.1038/leu.2015.343 Pan, 2002, Strategy for the treatment of acute myelogenous leukemia based on folate receptor beta-targeted liposomal doxorubicin combined with receptor induction using all-trans retinoic acid, Blood, 100, 594, 10.1182/blood.V100.2.594 Shi, 2013, Multistep targeted nano drug delivery system aiming at leukemic stem cells and minimal residual disease, Mol. Pharm., 10, 2479, 10.1021/mp4001266 Torchilin, 2000, Drug targeting, Eur. J. Pharm. Sci., 2, S81, 10.1016/S0928-0987(00)00166-4 Peer, 2007, Nanocarriers as an emerging platform for cancer therapy, Nat. Nanotechnol., 2, 751, 10.1038/nnano.2007.387 Beloqui, 2013, Biodistribution of Nanostructured Lipid Carriers (NLCs) after intravenous administration to rats: influence of technological factors, Eur. J. Pharm. Biopharm., 84, 309, 10.1016/j.ejpb.2013.01.029 Braet, 2012, AFM imaging of fenestrated liver sinusoidal endothelial cells, Micron, 43, 1252, 10.1016/j.micron.2012.02.010 Epelman, 2014, Origin and functions of tissue macrophages, Immunity, 41, 21, 10.1016/j.immuni.2014.06.013 Chavez-Santoscoy, 2012, Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using “pathogen-like” amphiphilic polyanhydride nanoparticles, Biomaterials, 33, 4762, 10.1016/j.biomaterials.2012.03.027 Vukman, 2013, Mannose receptor and macrophage galactose-type lectin are involved in Bordetella pertussis mast cell interaction, J. Leukoc. Biol., 94, 439, 10.1189/jlb.0313130 Wang, 2003, Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation, Nature, 421, 384, 10.1038/nature01339 Hofkens, 2011, Intravenously delivered glucocorticoid liposomes inhibit osteoclast activity and bone erosion in murine antigen-induced arthritis, J. Control Release, 152, 363, 10.1016/j.jconrel.2011.03.001 Kraft, 2014, Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems, J. Pharm. Sci., 103, 29, 10.1002/jps.23773 Goldberg, 2001, Binding of bone sialoprotein, osteopontin and synthetic polypeptides to hydroxyapatite, Connect. Tissue Res., 42, 25, 10.3109/03008200109014246 Bernards, 2008, MC3T3-E1 cell adhesion to hydroxyapatite with adsorbed bone sialoprotein, bone osteopontin, and bovine serum albumin, Colloids Surf. B Biointerfaces, 64, 236, 10.1016/j.colsurfb.2008.01.025 Gilbert, 2003, Biomimetic peptides that engage specific integrin-dependent signaling pathways and bind to calcium phosphate surfaces, J. Biomed. Mater Res. A, 67, 69, 10.1002/jbm.a.10053 Murphy, 2007, Synthesis and in vitro hydroxyapatite binding of peptides conjugated to calcium-binding moieties, Biomacromolecules, 8, 2237, 10.1021/bm070121s Ogawa, 2013, Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers, PLoS One, 8, 10.1371/journal.pone.0084335 Wang, 2007, Osteotropic Peptide that differentiates functional domains of the skeleton, Bioconjug. Chem., 18, 1375, 10.1021/bc7002132 Yarbrough, 2010, Specific binding and mineralization of calcified surfaces by small peptides, Calcif. Tissue Int., 86, 58, 10.1007/s00223-009-9312-0 Wang, 2010, Bisphosphonate-coated BSA nanoparticles lack bone targeting after systemic administration, J. Drug Target, 18, 611, 10.3109/10611861003622560 Wang, 2003, Synthesis and evaluation of water-soluble polymeric bone-targeted drug delivery systems, Bioconjug. Chem., 14, 853, 10.1021/bc034090j Pan, 2008, Biodistribution and pharmacokinetic studies of bone-targeting N-(2-hydroxypropyl)methacrylamide copolymer-alendronate conjugates, Mol. Pharm., 5, 548, 10.1021/mp800003u Santini, 2006, Mechanisms of disease: preclinical reports of antineoplastic synergistic action of bisphosphonates, Nat. Clin. Pract. Oncol., 3, 325, 10.1038/ncponc0520 Lander, 2012, What does the concept of the stem cell niche really mean today?, BMC Biol., 10, 19, 10.1186/1741-7007-10-19 Zhang, 2003, Identification of the haematopoietic stem cell niche and control of the niche size, Nature, 425, 836, 10.1038/nature02041 Calvi, 2003, Osteoblastic cells regulate the haematopoietic stem cell niche, Nature, 425, 841, 10.1038/nature02040 Sheppard, 2002, Endothelial integrins and angiogenesis: not so simple anymore, J. Clin. Invest., 110, 913, 10.1172/JCI0216713 Fiedler, 1997, Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia, Blood, 89, 1870, 10.1182/blood.V89.6.1870 Perez-Atayde, 1997, Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia, Am. J. Pathol., 150, 815 Shamay, 2016, Assessing the therapeutic efficacy of VEGFR-1-targeted polymer drug conjugates in mouse tumor models, J. Control Release, 229, 192, 10.1016/j.jconrel.2016.03.024 Neri, 2005, Tumour vascular targeting, Nat. Rev. Cancer, 5, 436, 10.1038/nrc1627 Jubeli, 2012, E-selectin as a target for drug delivery and molecular imaging, J. Control Release, 158, 194, 10.1016/j.jconrel.2011.09.084 Thorpe, 2004, Vascular targeting agents as cancer therapeutics, Clin. Cancer Res., 10, 415, 10.1158/1078-0432.CCR-0642-03 Steiner, 2011, Antibody-radionuclide conjugates for cancer therapy: historical considerations and new trends, Clin. Cancer Res., 17, 6406, 10.1158/1078-0432.CCR-11-0483 Pasche, 2012, Immunocytokines: a novel class of potent armed antibodies, Drug Discov. Today, 17, 583, 10.1016/j.drudis.2012.01.007 Bernardes, 2012, A traceless vascular-targeting antibody-drug conjugate for cancer therapy, Angew. Chem. Int. Ed. Engl., 51, 941, 10.1002/anie.201106527 Schliemann, 2015, Targeting interleukin-2 to the bone marrow stroma for therapy of acute myeloid leukemia relapsing after allogeneic hematopoietic stem cell transplantation, Cancer Immunol. Res., 3, 547, 10.1158/2326-6066.CIR-14-0179 Chen, 2000, In vitro and in vivo production of vascular endothelial growth factor by chronic lymphocytic leukemia cells, Blood, 96, 3181, 10.1182/blood.V96.9.3181 Krauth, 2004, Immunohistochemical detection of VEGF in the bone marrow of patients with chronic myeloid leukemia and correlation with the phase of disease, Am. J. Clin. Pathol., 121, 473, 10.1309/3JLTFNNEDQHB4A0P Eigentler, 2011, A dose-escalation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine for the therapy of patients with metastatic melanoma, Clin. Cancer Res., 17, 7732, 10.1158/1078-0432.CCR-11-1203 Johannsen, 2010, The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma, Eur. J. Cancer, 46, 2926, 10.1016/j.ejca.2010.07.033 Bevilacqua, 1993, Endothelial-leukocyte adhesion molecules, Annu. Rev. Immunol., 11, 767, 10.1146/annurev.iy.11.040193.004003 Zarbock, 2011, Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow, Blood, 118, 6743, 10.1182/blood-2011-07-343566 Winkler, 2012, Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance, Nat. Med., 18, 1651, 10.1038/nm.2969 Sipkins, 2005, In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment, Nature, 435, 969, 10.1038/nature03703 Mann, 2010, Identification of thioaptamer ligand against E-selectin: potential application for inflamed vasculature targeting, PLoS One, 5, 10.1371/journal.pone.0013050 Konopleva, 2011, Leukemia stem cells and microenvironment: biology and therapeutic targeting, J. Clin. Oncol., 29, 591, 10.1200/JCO.2010.31.0904 Korn, 2017, Myeloid malignancies and the microenvironment, Blood, 129, 811, 10.1182/blood-2016-09-670224 Ratnam, 2003, Receptor induction and targeted drug delivery: a new antileukaemia strategy, Expert Opin. Biol. Ther., 3, 563, 10.1517/14712598.3.4.563 Lim, 2010, Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine:daunorubicin formulation, in bone marrow xenografts, Leuk. Res., 34, 1214, 10.1016/j.leukres.2010.01.015 Gordon, 2016, CPX-351 exhibits potent and direct ex vivo cytotoxicity against AML blasts with enhanced efficacy for cells harboring the FLT3-ITD mutation, Leuk. Res., 53, 39, 10.1016/j.leukres.2016.12.002 Kim, 2011, Liposomal encapsulation of a synergistic molar ratio of cytarabine and daunorubicin enhances selective toxicity for acute myeloid leukemia progenitors as compared to analogous normal hematopoietic cells, Exp. Hematol., 39, 741, 10.1016/j.exphem.2011.04.001 U.S. Food & Drug Administration, 2017 Sun, 2014, Oligonucleotide aptamers: new tools for targeted cancer therapy, Mol. Ther. Nucleic Acids, 3, 10.1038/mtna.2014.32 Shum, 2013, Nucleic acid aptamers as potential therapeutic and diagnostic agents for lymphoma, J. Cancer Ther., 4, 872, 10.4236/jct.2013.44099 Shangguan, 2006, Aptamers evolved from live cells as effective molecular probes for cancer study, Proc. Natl. Acad. Sci. U. S. A., 103, 11838, 10.1073/pnas.0602615103 Duda, 2011, CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies?, Clin. Cancer Res., 17, 2074, 10.1158/1078-0432.CCR-10-2636 Hoellenriegel, 2014, The Spiegelmer NOX-A12, a novel CXCL12 inhibitor, interferes with chronic lymphocytic leukemia cell motility and causes chemosensitization, Blood, 123, 1032, 10.1182/blood-2013-03-493924 Gattoni-Celli, 2009, Overexpression of nucleolin in engrafted acute myelogenous leukemia cells, Am. J. Hematol., 84, 535, 10.1002/ajh.21461 Mongelard, 2010, AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia, Curr. Opin. Mol. Ther., 12, 107 Kikushige, 2010, TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells, Cell Stem Cell., 7, 708, 10.1016/j.stem.2010.11.014 Jan, 2011, Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker, Proc. Natl. Acad. Sci. U. S. A., 108, 5009, 10.1073/pnas.1100551108 Hira, 2017, Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches, Biochim. Biophys. Acta, 1868, 183 Miao, 2017, Nanoformulations for combination or cascade anticancer therapy, Adv. Drug Deliv. Rev., 115, 3, 10.1016/j.addr.2017.06.003 Hu, 2016, Recent advances of cocktail chemotherapy by combination drug delivery systems, Adv. Drug Deliv. Rev., 98, 19, 10.1016/j.addr.2015.10.022