Drug delivery in oncology from basic research to cancer therapy 1

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Weitere Verfasser: Kratz, Felix (HerausgeberIn)
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adam_text IMAGE 1 VII CONTENTS TO VOLUME 1 FOREWORD V PREFACE XVII LIST OF CONTRIBUTORS XIX DRUG DELIVERY IN ONCOLOGY - CHALLENGE AND PERSPECTIVES LIX PART I PRINCIPLES OF TUMOR TARGETING 1 1 LIMITS OF CONVENTIONAL CANCER CHEMOTHERAPY 3 KLAUS MROSS AND FELIX KRATZ 1.1 INTRODUCTION: THE ERA OF CANCER CHEMOTHERAPY 3 1.2 DILEMMA AND CHALLENGE OF TREATING MALIGNANT DISEASES 14 1.3 ADVERSE EFFECTS 16 1.3.1 COMMON SIDE-EFFECTS 18 1.3.1.1 DEPRESSION OF THE IMMUNE SYSTEM 18 1.3.1.2 FATIGUE 19 1.3.1.3 TENDENCY TO BLEED EASILY 19 1.3.1.4 GASTROINTESTINAL DISTRESS 19 1.3.1.5 HAIR LOSS 20 1.3.2 DAMAGE TO SPECIFIC ORGANS 20 1.3.2.1 CARDIOTOXICITY 20 1.3.2.2 HEPATOTOXICITY 21 1.3.2.3 NEPHROTOXICITY 22 1.3.2.4 PULMONARY SIDE-EFFECTS 22 1.3.2.5 VASCULAR ADVERSE EFFECTS 23 1.3.2.6 TISSUE DAMAGE (EXTRAVASATION) 23 1.3.2.7 NEUROLOGICAL SIDE-EFFECTS 24 1.3.2.8 SECONDARY NEOPLASMS 25 1.3.2.9 INFERTILITY 25 1.3.2.10 OTHER SIDE-EFFECTS 25 1.4 SUPPORTIVE CARE 25 1.5 NEW APPROACHES COMPLEMENTING CURRENT CANCER CHEMOTHERAPY 26 1.6 CONCLUSIONS AND PERSPECTIVES 2% REFERENCES 29 BIBLIOGRAFISCHE INFORMATIONEN HTTP://D-NB.INFO/1011200406 DIGITALISIERT DURCH IMAGE 2 VIII CONTENTS 2 PATHOPHYSIOLOGICAL AND VASCULAR CHARACTERISTICS OF SOLID TUMORS IN RELATION TO DRUG DELIVERY 33 PETER VAUPEL 2.1 INTRODUCTION 33 2.2 BASIC PRINCIPLES OF BLOOD VESSEL FORMATION IN SOLID TUMORS 34 2.2.1 ANGIOGENESIS 34 2.2.2 VASCULAR CO-OPTION 36 2.2.3 VASCULOGENESIS 36 2.2.4 INTUSSUSCEPTION 36 2.2.5 VASCULAR MIMICRY 36 2.2.6 MICROVESSEL FORMATION BY MYELOID CELLS 36 2.3 TUMOR LYMPHANGIOGENESIS 37 2.4 TUMOR VASCULARITY AND BLOOD FLOW 37 2.5 ARTERIOVENOUS SHUNT PERFUSION IN TUMORS 38 2.6 VOLUME AND CHARACTERISTICS OF THE TUMOR INTERSTITIAL SPACE 40 2.7 INTERSTITIAL FLUID PRESSURE IN TUMORS 42 2.8 ROLE OF THE DISORGANIZED, COMPROMISED MICROCIRCULATION AS AN OBSTACLE IN DRUG DELIVERY 43 2.8.1 BLOOD-BORNE DELIVERY 43 2.8.2 EXTRAVASATION OF ANTICANCER AGENTS 45 2.9 INTERSTITIAL BARRIERS TO DRUG DELIVERY 46 2.10 PATHOPHYSIOLOGICAL TUMOR MICROENVIRONMENT AS AN OBSTACLE IN TUMOR THERAPY 47 2.10.1 HYPOXIA AS AN OBSTACLE IN DRUG THERAPY 48 2.10.1.1 DIRECT EFFECTS 48 2.10.1.2 INDIRECT EFFECTS BASED ON CHANGES IN THE TRANSCRIPTOME, IN DIFFERENTIAL REGULATION OF GENE EXPRESSION, AND IN ALTERATIONS OF THE PROTEOME 49 2.10.1.3 INDIRECT EFFECTS BASED ON ENHANCED MUTAGENESIS, GENOMIC INSTABILITY, AND CLONAL SELECTION 51 2.10.1.4 TUMOR HYPOXIA: AN ADVERSE PARAMETER IN CHEMOTHERAPY 51 2.10.2 TUMOR ACIDOSIS AND DRUG RESISTANCE 53 2.11 CONCLUSIONS 56 ACKNOWLEDGMENTS 56 REFERENCES 56 3 ENHANCED PERMEABILITY AND RETENTION EFFECT IN RELATION TO TUMOR TARGETING 65 HIROSHI MAEDA 3.1 BACKGROUND AND STATUS QUO 65 3.2 WHAT IS THE EPR EFFECT: MECHANISM, UNIQUENESS, AND FACTORS INVOLVED 66 3.3 HETEROGENEITY OF THE EPR EFFECT: A PROBLEM IN DRUG DELIVERY 72 3.4 OVERCOMING THE HETEROGENEITY OF THE EPR EFFECT FOR DRUG DELIVERY AND HOW TO ENHANCE THE EPR EFFECT 75 3.4.1 ANGIOTENSIN II-INDUCED HIGH BLOOD PRESSURE 75 IMAGE 3 CONTENTS IX 3.4.2 USE OF NO-RELEASING AGENTS 78 3.4.3 USE OF OTHER VASCULAR MODULATORS 79 3.5 PEG DILEMMA: STEALTH EFFECT AND ANTI-PEG IGM ANTIBODY 79 3.6 CONCLUDING REMARKS 80 ACKNOWLEDGMENTS 81 REFERENCES 81 4 PHARMACOKINETICS OF IMMUNOGLOBULIN C AND SERUM ALBUMIN: IMPACT OF THE NEONATAL FC RECEPTOR ON DRUG DESIGN 85 JAN TERJE ANDERSEN AND JUGER SANDLIE 4.1 INTRODUCTION 85 4.2 DISCOVERY OF FCRN 87 4.3 FCRN STRUCTURE 88 4.4 FCRN-LIGAND INTERACTIONS 89 4.5 FCRN AS A MULTIPLAYER WITH THERAPEUTIC UTILITIES 90 4.5.1 DIRECTIONAL PLACENTAL TRANSPORT 90 4.5.2 FCRN AT MUCOSAL SURFACES 91 4.5.3 SYSTEMIC FCRN-MEDIATED RECYCLING 92 4.5.4 ROLE OF FCRN IN ANTIGEN PRESENTATION 93 4.5.5 FCRN AT IMMUNE-PRIVILEGED SITES 94 4.5.6 FCRN IN THE KIDNEYS 94 4.5.7 FCRN EXPRESSED BY THE LIVER 95 4.6 ENGINEERING IGG FOR ALTERED FCRN BINDING AND PHARMACOKINETICS 95 4.6.1 IGG FC FUSIONS 95 4.6.2 ENGINEERED IGG VARIANTS 96 4.6.3 BLOCKING FCRN RECYCLING 102 4.7 TARGETING FCRN BY SA 102 4.7.1 SA FUSIONS 102 4.7.2 TARGETING SA 105 4.8 CONSIDERING CROSS-SPECIES BINDING 111 4.9 CONCLUDING REMARKS 113 ACKNOWLEDGMENT 113 REFERENCES 113 5 DEVELOPMENT OF CANCER-TARGETING LIGANDS AND LIGAND-DRUG CONJUGATES 121 RUIWU LIU, KAI XIAO, JUNTAO LUO, AND KIT S. LAM 5.1 INTRODUCTION 121 5.2 OVERVIEW OF CANCER-TARGETING LIGAND-DRUG CONJUGATES 122 5.3 CANCER-TARGETING LIGANDS 125 5.3.1 INTRODUCTION 125 5.3.2 PHAGE-DISPLAY LIBRARY APPROACH 125 5.3.2.1 PHAGE-DISPLAY LIBRARY SCREENING AND DECODING J27 5.3.2.2 EXAMPLES 127 IMAGE 4 X I CONTENTS 5.3.3 OBOC COMBINATORIAL LIBRARY APPROACH 131 5.3.3.1 OBOC LIBRARY DESIGN 132 5.3.3.2 OBOC LIBRARY CONSTRUCTION 135 5.3.3.3 OBOC LIBRARY SCREENING 137 5.3.3.4 OBOC LIBRARY DECODING 138 5.3.3.5 IIGAND OPTIMIZATION 139 5.3.3.6 EXAMPLES 140 5.4 LINKERS 143 5.4.1 ACID-SENSITIVE LINKERS 143 5.4.2 ENZYMATIC CLEAVAGE 143 5.4.3 SELF-IMMOLATIVE SPACERS 145 5.4.4 REDUCTIVE CLEAVAGE 146 5.4.5 ON-DEMAND CLEAVABLE LINKER 146 5.5 EXAMPLES OF CANCER-TARGETING LIGAND-DRUG CONJUGATES 147 5.5.1 FOLK ACID-DRUG CONJUGATES 147 5.5.2 PEPTIDE LIGAND-DRUG CONJUGATES 148 5.5.3 PEPTIDE HORMONE-DRUG CONJUGATES 150 5.5.4 ANTIBODY-DRUG CONJUGATES 151 5.5.5 ADEPT 154 5.5.6 POLYMER-DRUG CONJUGATES 156 5.5.7 TARGETING LIPOSOMES AND NANOPARTIDES 158 5.6 CONCLUSIONS AND PERSPECTIVES 159 ACKNOWLEDGMENTS 160 REFERENCES 160 6 ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) - BASIC PRINCIPLES AND ITS PRACTICE SO FAR 169 KENNETH D. BAGSHAWE 6.1 INTRODUCTION 169 6.2 PRINCIPLES AND THE COMPONENTS OF ADEPT 170 6.2.1 TARGET 170 6.2.2 ANTIBODY 171 6.2.3 ENZYME 172 6.2.4 PRODRUG AND DRUG 173 6.3 THIRD ESSENTIAL 173 6.4 ADEPT STUDIES ELSEWHERE 175 6.5 REAGENTS FOR FIRST CLINICAL TRIALS IN LONDON (1990-1995) 176 6.5.1 FIRST ADEPT CLINICAL TRIAL 1 77 6.5.2 SUBSEQUENT ADEPT CLINICAL STUDIES IN LONDON 178 6.5.3 TWO-PHASE ADEPT CLINICAL STUDIES IN LONDON 179 6.6 TECHNOLOGY ADVANCES 179 6.7 ADEPT FUTURE 181 REFERENCES 181 IMAGE 5 CONTENTS XI PART II TUMOR IMAGING 187 7 IMAGING TECHNIQUES IN DRUG DEVELOPMENT AND CLINICAL PRACTICE 189 JOHN C. CHANG, SANJIV S. GAMBHIR, AND JUERGEN K. WILLMANN 7.1 INTRODUCTION 189 7.2 CANCER BIOLOGY 191 7.2.1 TUMOR GENETIC HETEROGENEITY 191 7.2.2 ALTERED TUMOR METABOLISM 191 7.2.3 TUMOR ANGIOGENESIS 192 7.2.4 RECEPTOR PATHOLOGIES 194 7.3 CANCER BIOMARKERS 194 7.3.1 HISTOLOGICAL BIOMARKERS 194 7.3.2 HEMATOLOGICAL BIOMARKERS 196 7.3.3 IMAGING BIOMARKERS 196 7.4 IMAGING TECHNIQUES 197 7.4.1 SPECT 197 7.4.2 PET/PET-CT 198 7'.4.3 MRI 198 7.4.4 CT 199 7.4.5 ULTRASOUND 199 7.4.6 FLUORESCENCE/BIOLUMINESCENCE 200 7.5 EXAMPLES OF IMAGING ASSESSMENT OF TUMOR RESPONSE 200 7.5.1 SPECT 200 7.5.2 PET/PET-CT 201 7.5.2.1 MICRODOSING 201 7.5.2.2 CANCER METABOLISM AND PROLIFERATION 202 7.5.2.3 HYPOXIA 204 7.5.2.4 BIOMARKER IMAGING 205 7.5.2.5 ANGIOGENESIS 207 7.5.2.6 APOPTOSIS 207 7.5.3 MRI 207 7.5.3.1 CELLULAR STRUCTURE 209 7.5.3.2 METABOLIC RESPONSE 209 7.5.3.3 TUMOR PERFUSION 210 7.5.4 CT IMAGING 211 7.5.5 ULTRASOUND 212 7.5.6 FLUORESCENCE/BIOLUMINESCENCE 213 7.6 CHALLENGES OF IMAGING IN DRUG DEVELOPMENT AND VALIDATION 214 7.7 CONCLUSIONS AND FUTURE PERSPECTIVES 215 REFERENCES 217 8 MAGNETIC NANOPARTICLES IN MAGNETIC RESONANCE IMAGING AND DRUG DELIVERY 225 PATRICK D. SUTPHIN, EFRENJ. FLORES, AND MUKESH HARISINGHANI 8.1 INTRODUCTION 225 IMAGE 6 XIII CONTENTS 8.2 PASSIVE TARGETING OF NANOPARTICLES 227 8.2.1 MECHANISM OF ACTION 229 8.2.2 LYMPHOTROPIC NANOPARTICLE MRI 229 8.3 ACTIVE SPIO NANOPARTICLE TARGETING 232 8.3.1 CREATING THE TARGETED IMAGING AGENTS 233 8.3.1.1 TRANSFERRIN-USPIO NANOPARTICLES 233 8.3.1.2 FOLATE RECEPTOR 235 8.3.1.3 INTEGRINS 235 8.4 NANOPARTICLES IN TARGETED THERAPY 236 8.4.1 NANOPARTICLES IN GENE THERAPY 237 8.4.2 NANOPARTICLES IN MOLECULARLY TARGETED DRUG DELIVERY 238 8.4.3 CONVERSION OF THERAPEUTIC AGENT TO IMAGING AGENT 239 8.4.4 TOXIC PAYLOAD 240 8.5 CONCLUSIONS 240 REFERENCES 242 9 PRECLINICAL AND CLINICAL TUMOR IMAGING WITH SPECT/CT AND PET/CT 247 ANDREAS K. BUCK, FLORIAN GAERTNER, AMBROS BEER, KEN HERRMANN, SIBYLLE ZIEGLER, AND MARKUS SCHWAIGER 9.1 INTRODUCTION 247 9.2 TECHNICAL ASPECTS OF FUNCTIONAL AND MOLECULAR IMAGING WITH SPECT AND PET 249 9.2.1 PRINCIPLES OF CLINICAL PET AND HYBRID PET/CT IMAGING 249 9.2.2 BIOMARKERS FOR PET AND PET/CT IMAGING 250 9.2.3 PRINCIPLES OF CLINICAL SPECT AND HYBRID SPECT CT IMAGING 252 9.2.4 BIOMARKERS FOR SPECT AND SPECT/CT IMAGING 258 9.2.5 PRINCIPLES OF PRECLINICAL IMAGING WITH SPECT AND PET 258 9.3 PRECLINICAL AND CLINICAL DEVELOPMENTS 260 9.3.1 IMAGING NEOANGIOGENESIS 260 9.3.1.1 VEGF/VEGFR IMAGING 261 9.3.1.2 RADIOLABELED INTEGRIN ANTAGONISTS (RGD PEPTIDES) 262 9.3.1.3 MONOMERIC TRACER LABELING STRATEGIES 262 9.3.2 IMAGING THE PROLIFERATIVE ACTIVITY OF TUMORS 264 9.3.3 IMAGING THE HYPOXIE CELL FRACTION OF TUMORS 267 9.3.4 IMAGING RECEPTOR EXPRESSION 269 9.4 CLINICAL APPLICATIONS OF SPECT/CT AND PET 272 9.4.1 DIFFERENTIATION OF BENIGN FROM MALIGNANT TUMORS AND CANCER DETECTION 272 9.4.2 STAGING OF CANCER: PROGNOSTIC POTENTIAL OF IMAGING BIOMARKERS 273 9.4.3 ASSESSMENT OF RESPONSE TO THERAPY 274 9.4.4 RESTAGINGOF CANCER AND DETECTION OF RECURRENCE 274 9.4.5 PET FOR RADIATION TREATMENT PLANNING 275 9.4.6 PET FOR CANCER DRUG DEVELOPMENT 275 9.4.7 SPECT/CT FOR MAPPING OF SLNS 276 IMAGE 7 CONTENTS XIII 9.4.8 SPECT/CT FOR DETECTION OF BONE METASTASES 277 9.4.9 SPECT/CT IN THYROID CANCER 278 9.4.10 SPECT/CT FOR IMAGING OF ADRENOCORTICAL TUMORS 279 9.4.11 SPECT/CT IN NEUROENDOCRINE TUMORS 281 9.5 CONCLUSIONS AND PERSPECTIVES 281 REFERENCES 282 CONTENTS TO VOLUME 2 PART III MACROMOLECULAR DRUG DELIVERY SYSTEMS 289 ANTIBODY-BASED SYSTEMS 289 10 EMPOWERED ANTIBODIES FOR CANCER THERAPY 291 STEPHEN C. ALLEY, SIMONE JEGER, ROBERT P. LYON, DJANGO SUSSMAN, AND PETER D. SENTER 11 MAPPING ACCESSIBLE VASCULAR TARGETS TO PENETRATE ORGANS AND SOLID TUMORS 325 KERRI A. MASSEY AND JAN E. SCHNITZER 12 CONSIDERATIONS OF LINKER TECHNOLOGIES 355 LAURENT DUCRY 13 ANTIBODY-MAYTANSINOID CONJUGATES: FROM THE BENCH TO THE CLINIC 375 HANS ERICKSON 14 CALICHEAMICIN ANTIBODY-DRUG CONJUGATES AND BEYOND 395 PUJA SAPRA, JOHN DIJOSEPH, AND HANS-PETER GERBER 15 ANTIBODIES FOR THE DELIVERY OF RADIONUCLIDES 411 ANNA M. WU 16 BISPECIFIC ANTIBODIES AND IMMUNE THERAPY TARGETING 441 SERGEJ M. KIPRIJANOV POLYMER-BASED SYSTEMS 483 17 DESIGN OF POLYMER-DRUG CONJUGATES 485 JINDFICH KOPEIEK AND PAVLA KOPEIKOVA 18 DENDRITIC POLYMERS IN ONCOLOGY: FACTS, FEATURES, AND APPLICATIONS 513 MOHIUDDIN ABDUL QUADIR, MARCELO CALDERON, AND RAINER HAAG IMAGE 8 XIV CONTENTS 19 SITE-SPECIFIC PRODRUG ACTIVATION AND THE CONCEPT OF SELF-IMMOLATION 553 ANDRE WARNECKE 20 LIGAND-ASSISTED VASCULAR TARGETING OF POLYMER THERAPEUTICS 591 ANAT ELDAR-BOOCK, DINA POLYAK, AND RONIT SATCHI-FAINARO 21 DRUG CONJUGATES WITH POLYJETHYLENE CLYCOL) 627 HONG ZHAO, LEE M. GREENBERGER, AND IVAN D. HORAK 22 THERMO-RESPONSIVE POLYMERS 667 DRAZEN RAUCHER AND SHAMA MOKTAN 23 POLYSACCHARIDE-BASED DRUG CONJUGATES FOR TUMOR TARGETING 701 GURUSAMY SARAVANAKUMAR, JAE HYUNG PARK, KWANGMEYUNG KIM, AND ICK CHAN KWON 24 SERUM PROTEINS AS DRUG CARRIERS OF ANTICANCER AGENTS 747 FELIX KRATZ, ANDREAS WUNDER, AND BAKHEET ELSADEK 25 FUTURE TRENDS, CHALLENGES, AND OPPORTUNITIES WITH POLYMER-BASED COMBINATION THERAPY IN CANCER 805 CORALIE DELADRIERE, RUT LUCAS, AND MARIA J. VICENT 26 CLINICAL EXPERIENCE WITH DRUG-POLYMER CONJUGATES 839 KHALID ABU AJAJ AND FELIX KRATZ PART IV NANO- AND MICROPARTICULATE DRUG DELIVERY SYSTEMS 885 LIPID-BASED SYSTEMS 885 27 OVERVIEW ON NANOCARRIERS AS DELIVERY SYSTEMS 887 HAIFA SHEN, ELVIN BLANCO, BIANA GODIN, RITA E. SERDA, AGATHE K. STREIFF, AND MAURO FERRARI 28 DEVELOPMENT OF PEGYLATED LIPOSOMES 907 I. CRAIG HENDERSON 29 IMMUNOLIPOSOMES 951 VLADIMIR P. TORCHILIN 30 RESPONSIVE LIPOSOMES (FOR SOLID TUMOR THERAPY) 989 STAVROULA SOFOU IMAGE 9 CONTENTS XV 31 NANOSCALE DELIVERY SYSTEMS FOR COMBINATION CHEMOTHERAPY 1013 BARRY D. LIBOIRON, PAUL G. TARDI, TROY O. HARASYM, AND LAWRENCE, D. MAYER POLYMER-BASED SYSTEMS 1051 32 MICELLAR STRUCTURES AS DRUG DELIVERY SYSTEMS 1053 NOBUHIRO NISHIYAMA, HORACIO CABRAI, AND KAZUNORI KATAOKA 33 TAILOR-MADE HYDROGELS FOR TUMOR DELIVERY 1071 SUNGWON KIM AND KINAM PARK 34 PH-TRIGGERED MICELLES FOR TUMOR DELIVERY 1099 HAIQING YIN AND YOU HAN BAE 35 ALBUMIN-DRUG NANOPARTICLES 1133 NEIL DESAI 36 CARBON NANOTUBES 1163 DAVID A. SCHEINBERG, CARLOS H. VILLA, FREDDY ESCORDA, AND MICHAEL R. MCDEVITT CONTENTS TO VOLUME 3 PART V LIGAND-BASED DRUG DELIVERY SYSTEMS 1187 37 CELL-PENETRATING PEPTIDES IN CANCER TARGETING 1189 KAIDO KURRIKOFF, JULIA SUHORUTSENKO, AND UELO LANGEL 38 TARGETING TO PEPTIDE RECEPTORS 1219 ANDREW V. SCHALLY AND GABOR HALMOS 39 APTAMER CONJUGATES: EMERGING DELIVERY PLATFORMS FOR TARGETED CANCER THERAPY 1263 ZEYU XIAO, JULIAN FRIEDER, BENJAMIN A. TEPLY, AND OMID C. FAROKHZAD 40 DESIGN AND SYNTHESIS OF DRUG CONJUGATES OF VITAMINS AND GROWTH FACTORS 1283 IONTCHO R. VLAHOV, PAULJ. KLEINDL, AND FEI YOU 41 DRUG CONJUGATES WITH POLYUNSATURATED FATTY ACIDS 1323 JOSHUA SEITZ AND IWAO OJIMA IMAGE 10 XVI I CONTENTS PART VI SPECIAL TOPICS 1359 42 RNA DRUG DELIVERY APPROACHES 1361 YUAN ZHANG AND LEAF HUANG 43 LOCAL GENE DELIVERY FOR THERAPY OF SOLID TUMORS 1391 WOLFGANG WALTHER, PETER M. SCHLAG, AND ULRIKE STEIN 44 VIRAL VECTORS FOR RNA INTERFERENCE APPLICATIONS IN CANCER RESEARCH AND THERAPY 1415 HENRY FECHNER AND JENS KURRECK 45 DESIGN OF TARGETED PROTEIN TOXINS 1443 HENDRIK FUCHS AND CHRISTOPHER BACHRAN 46 DRUG TARGETING TO THE CENTRAL NERVOUS SYSTEM 1489 GERT FRICKER, ANNE MAHRINGER, MELANIE OTT, AND VALESKA REICHEL 47 LIVER TUMOR TARGETING 1519 KATRIN HOCHDOERFFER, GIUSEPPINA DI STEFANO, HIROSHI MAEDA, AND FELIX KRATZ 48 PHOTODYNAMIC THERAPY: PHOTOSENSITIZER TARGETING AND DELIVERY 1569 PAWEL MROZ, SULBHA K. SHARMA, TIMUR ZHIYENTAYEV, YING-YING HUANG, AND MICHAEL R. HAMBLIN 49 TUMOR-TARGETING STRATEGIES WITH ANTICANCER PLATINUM COMPLEXES 1605 MARKUS GALANSKI AND BERNHARD K. KEPPLER INDEX 1631
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spelling Drug delivery in oncology from basic research to cancer therapy 1 ed. by Felix Kratz ...
Weinheim Wiley-VCH 2012
LXXXV, 288 S. Ill., graph. Darst. 25 cm
txt rdacontent
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nc rdacarrier
Wirkstofffreisetzung (DE-588)4190018-2 gnd rswk-swf
Cytostatikum (DE-588)4068347-3 gnd rswk-swf
(DE-588)4143413-4 Aufsatzsammlung gnd-content
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Wirkstofffreisetzung (DE-588)4190018-2 s
DE-604
Kratz, Felix edt
(DE-604)BV040416114 1
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spellingShingle Drug delivery in oncology from basic research to cancer therapy
Wirkstofffreisetzung (DE-588)4190018-2 gnd
Cytostatikum (DE-588)4068347-3 gnd
subject_GND (DE-588)4190018-2
(DE-588)4068347-3
(DE-588)4143413-4
title Drug delivery in oncology from basic research to cancer therapy
title_auth Drug delivery in oncology from basic research to cancer therapy
title_exact_search Drug delivery in oncology from basic research to cancer therapy
title_full Drug delivery in oncology from basic research to cancer therapy 1 ed. by Felix Kratz ...
title_fullStr Drug delivery in oncology from basic research to cancer therapy 1 ed. by Felix Kratz ...
title_full_unstemmed Drug delivery in oncology from basic research to cancer therapy 1 ed. by Felix Kratz ...
title_short Drug delivery in oncology
title_sort drug delivery in oncology from basic research to cancer therapy
title_sub from basic research to cancer therapy
topic Wirkstofffreisetzung (DE-588)4190018-2 gnd
Cytostatikum (DE-588)4068347-3 gnd
topic_facet Wirkstofffreisetzung
Cytostatikum
Aufsatzsammlung
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