S P R I N G E R B R I E F S I N A P P L I E D S C I E N C E S A N D T E C H N O LO G Y NANOTHERANOST ICS

P. Gopinath · S. Uday KumarIshita Matai · Bharat BhushanDeepika Malwal · Abhay SachdevPoornima Dubey

Cancer Nanotheranostics

SpringerBriefs in Applied Sciences and Technology

Nanotheranostics

Series editors

Tamil Selvan Subramanian, Singapore, SingaporeKarthikeyan Narayanan, Singapore, SingaporePadmanabhan Parasuraman, Singapore, SingaporePaulmurugan Ramasamy, Palo Alto, USA

More information about this series at http://www.springer.com/series/13040

http://www.springer.com/series/13040

P. Gopinath · S. Uday Kumar · Ishita Matai Bharat Bhushan · Deepika Malwal Abhay Sachdev · Poornima Dubey

1 3

Cancer Nanotheranostics

P. GopinathCentre for Nanotechnology Department of Biotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

S. Uday KumarCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

Ishita MataiCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

Bharat BhushanCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

ISSN 2191-530X ISSN 2191-5318 (electronic)SpringerBriefs in Applied Sciences and TechnologyISSN 2197-6740 ISSN 2197-6759 (electronic)NanotheranosticsISBN 978-981-287-434-4 ISBN 978-981-287-435-1 (eBook)DOI 10.1007/978-981-287-435-1

Library of Congress Control Number: 2015932514

Springer Singapore Heidelberg New York Dordrecht London© The Author(s) 2015This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made.

Printed on acid-free paper

Springer Science+Business Media Singapore Pte Ltd. is part of Springer Science+Business Media (www.springer.com)

Deepika MalwalCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

Abhay SachdevCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

Poornima DubeyCentre for Nanotechnology Indian Institute of Technology RoorkeeRoorkeeIndia

v

Preface

Diagnose the illness, trace its cause, seek the proper remedy and apply it with skill.

—Thirukural (Verse 948) by Thiruvalluvar, a Tamil Poet (2 B.C–8 A.D)

Inspite of being the major cause of death, efficient cancer therapy and its early diagnosis remains elusive for the researchers around the world. With the advent of new nanomaterials, the present century has revolutionized the application of nanoscale formulations for healthcare applications, especially in the field of cancer therapy or diagnosis. These nanoscale materials by virtue of their small dimension and improved therapeutic and diagnostic efficacy against cancer have transcended to the next generation of nanoscale formulations capable of achieving cancer ther-apy and diagnosis simultaneously. Such multifunctional nanoscale formulations would invariantly consist of therapeutic and diagnostic components combined together within a nanoscale carrier molecule. Realizing such multifunctional thera-nostic systems in the imminent future can reinvent the current cancer management strategies.

In concert with the aforementioned theme, this book would provide a clear insight into the recent advances in the field of cancer theranostics with special emphasis on nanoscale carrier molecules (polymeric, protein and lipid based) and imaging agents (organic and inorganic).

vii

Acknowledgments

Sincere thanks to the Science and Engineering Research Board (No. SR/FT/LS-57/2012) and Department of Biotechnology (No.BT/PR6804/GBD/27/486/2012), Government of India, for the financial support to conduct research in “Cancer Nanotheranostics” field.

ix

Contents

Cancer Nanotheranostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Cancer Nanotheranostics: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . 1

1.1 Polymer Based Nanotheranostics . . . . . . . . . . . . . . . . . . . . . . . . . 22 Dendrimers: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.1 Dendrimers as Drug Carriers . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112.2 Dendrimers for Tumor Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . 152.3 Dendrimers as Carriers for Theranostic Agents . . . . . . . . . . . . . . 17

3 Porphyrins as Cancer Theranostic Agents . . . . . . . . . . . . . . . . . . . . . . . . 203.1 Porphyrins as Photodynamic Therapy (PDT) Agents . . . . . . . . . 213.2 Porphyrins as Photo Thermal Therapy (PTT) Agents . . . . . . . . . 233.3 Porphyrins as Bioimaging Agents . . . . . . . . . . . . . . . . . . . . . . . . 273.4 Porphyrin Based Nanoparticles (Porphysomes) . . . . . . . . . . . . . . 30

4 Carbon Dots: Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314.1 C-Dots as Bioimaging Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 344.2 C-Dots as Theranostic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

5 Protein Based Nanoparticles: Introduction . . . . . . . . . . . . . . . . . . . . . . . 415.1 Albumins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425.2 Gelatin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505.3 Protein Nanocages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 565.4 Lectin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615.5 Therapeutic Protein and Peptide Based Nanoparticles . . . . . . . . 635.6 Other Protein Based Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . 65

6 Solid Lipid Nanoparticles (SLN): Introduction . . . . . . . . . . . . . . . . . . . . 656.1 SLN: A Versatile Nanocarrier. . . . . . . . . . . . . . . . . . . . . . . . . . . . 676.2 Synthesis of SLN Using Different Techniques . . . . . . . . . . . . . . 686.3 SLN for Cancer Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 766.4 SLN for Cancer Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 836.5 SLN as Theranostic Agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 856.6 Molecular Mechanism of Cellular Uptake . . . . . . . . . . . . . . . . . . 866.7 Drug Delivery Routes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87

http://dx.doi.org/10.1007/978-981-287-435-1_1http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec1http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec2http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec8http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec9http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec12http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec13http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec14http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec15http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec16http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec17http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec18http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec19http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec20http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec23http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec24http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec25http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec28http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec29http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec34http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec35http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec36http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec37http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec38http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec39http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec51http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec56http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec57http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec58http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec59

Contentsx

6.8 Drawbacks of SLN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 906.9 Other Lipid Based Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . 91

7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95

http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec64http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec68http://dx.doi.org/10.1007/978-981-287-435-1_1#Sec72

xi

Abbreviations

4T1 Murine breast cancer cell5-FU 5-FluorouracilA549 Human lung cancer cellADC Antibody-drug conjugateAft ApoferritinAMF AC magnetic fieldAnti-CEA Anti-carcinoembryonic antigen antibodiesAnti-TAG-72 Tumor associated glycoprotein-72 monoclonal antibodiesARPE-19 Human retinal pigmented epithelium cellATF Amino-terminal fragmentATRP Atom transfer radical polymerizationAu GoldAu-DENPs Dendrimer-entrapped gold nanoparticlesB16 Murine melanoma cell lineBBB Blood–brain barrierBCECs Capillary endothelial cellsBHHBB 1,2-bis[40-(100,100,100,20 0,20

0,300,300-heptafluoro-400,60 0-hexanedion- 600-yl)-benzyl]-benzene

BOPP 4-bis-(a, b-didihidroxyethyl)-deutero-porphyrin IXBPA BorophenylalanineBPT 2-(N,N-diethylanilin-4-yl)-4,6-bis

(pyrazol-1-yl)-1,3,5-triazineBSA Bovine serum albuminBT474 Human breast carcinoma cell lineBTZ BortezomibC32 Human amelanotic melanoma cell lineC6 Glioma cellsCaco-2 Human epithelial colorectal adenocarcinoma fibroblastsCAFs Cancer-associated fibroblasts

Abbreviationsxii

CANIR Carboxylic acid derivative of the NIR dye IR-783CAPAN-1 Metastatic pancreatic cancer cellCBSA Cationic BSACDDP CisplatinC-dots Carbon dotsCe6 Chlorin e6C-gel Cationic gelatinChS-CS Chondroitin sulfate-chitosanCon A Concanavalin ACPMV Cowpea mosaic virusCPZ Mono-substituted β-carboxy phthalocyanine zincCREKA Cys-Arg-GluLys-AlaCS-EA N- Carboxyethyl chitosan esterCT Computed tomographydBSA Denatured BSADC Dendritic cellDEVD Asp-Glu-Val-AspDIM-CpPhC6H5 (DIM-P) c-substituted diindolylmethanesDNA Deoxyribonucleic acidDNCs Dendrimer nanoclustersDOTA 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acidDox DoxorubicinDPA DipicolylamineDTPA Diethylenetriaminepentaacetic acidECGC Epigallocatechin gallateEGF Epithelial growth factorEGFR Epidermal growth factor receptorEph Erythropoietin-producing hepatomaEPR Enhanced permeability and retentionEu EuropiumFA Folic acidFAM CarboxyfluoresceinFAP Fibroblast activation proteinFAR Folic acid receptorFDA Food and Drug AdministrationFITC Fluorescein isothiocyanateFmp Fibronectin-mimetic peptideFMT Fluorescent molecular tomographyFNPs Fibrinogen nanoparticlesFR Folate receptorFRET Fluorescence resonance energy transferGd GadoliniumGd-HP-DO3A Gadolinium 1,4,7-tris(carboxymethyl)-

10-(2'-hydroxypropyl)-1,4,7,10-tetraazacyclododecane

Abbreviations xiii

GFP Green fluorescent proteinGLuc Gaussia luciferaseGNS Graphene nanosheetsGNs Gelatin nanospheresGRAS Generally recognized as safeHA Hyaluronic acidHCC Human hepatocellular carcinomaHCDs Hollow C-dotsHCRSV Hibiscus chlorotic ringspot virusHCT 116 Human colorectal cancer cellHela cells Human tumor cell lineHepG2 Human hepatoma cell lineHepli cells Human normal liver cellsHer HerceptinHFn Human H-chain ferritinHft Human ferritinHGF Hepatocyte growth factorhGSA Galactosyl HSAHINP HSA coated iron oxide nanoparticlesHIV Human immunodeficiency virusHNSCC Head and neck squamous cell carcinomaHP HematoporphyrinHPH High pressure homogenizationHSA Human serum albuminHsp Heat shock proteinHT1080 Human fibrosarcoma cellHT-29 Colorectal cancer celli.v. IntravenousIFN-γ Interferon gammaIL InterleukinIONPs Iron oxide nanoparticlesJ774 Murine macrophage-like cellsJNK c-Jun N-terminal kinasesK562 Leukemic cell lineKB Oral cancer cell lineL929 Mouse fibroblast cell lineLA Lactobionic acidLAPTM4B Lysosomal protein transmembrane 4 betaLf LactoferrinLMW Low molecular weightLTB Heat-labile enterotoxin subunit BLuPO4 Lutetium phosphatemAb Monoclonal antibodyMCF-10A Normal breast epithelial cells

Abbreviationsxiv

MCF-7 Human breast cancer cellsMDA-MB-231 Breast cancer cellsMDA-MB-435S Human melanoma cellMDA-MD-231 Breast cancer cell lineMFH Magnetic fluid hyperthermiaMGC803 Gastric cancer cellMMPs Matrix metalloproteinasesmPEG Methoxy-poly(ethylene glycol)mPEG 2000 Poly(ethylene glycol) methyl ether 2000MRI Magnetic resonance imagingMSN Mesoporous silica nanoparticlesMTX MethotrexateMWCNT Multiwalled carbon nanotubeMX MitoxantroneNano-rGO Reduced graphene oxideNCs NanoclustersNFs NanoflowersNHS N-hydroxysuccinimideNIH/3T3 Mouse embryonic fibroblast cellsNIR Near infrared regionNIRF Near-infrared fluorescenceNLCs Nanostructured lipid carriersNOTA 1,4,7-Triazacyclononane-N,N′,N′′-triacetic acidNPs NanoparticlesO/W emulsion Oil in water emulsionOVCAR-3 Ovarian cancer cellOVCAR-5 Human ovarian cancer cellsPAA Poly(acrylic acid)PAH Poly(allylamine hydrochloride)PAMAM Poly(amidoamine)PBS Phosphate buffer salinePc PhthalocyaninePC3 Prostatic Small Cell CarcinomaPCL Poly(3-caprolactone)PDI Photodynamic imagingPDMA Poly(dimethylamino) ethyl methacrylatepDNA plasmid DNAPDT Photodynamic therapyPE PolyelectrolytesPEA PhosphatidylethanolaminePEG Poly(ethylene glycol)PEG–PBLA Poly(ethylene glycol)–poly(benzyl L-aspartate)PEI PoltethyleneiminePET Positron emission tomography

Abbreviations xv

Pf-Fn Pyrococcus furiosus ferritinPFVCN Poly[9,9′-bis(6,6′-(N,N,N-trimethylaminium)-

fluorene-2,7-ylenevinylene-co-alt-2,5-dicyano-1,4-phenylene]PHA PolyhydroxyalkanoatePHEMA-g-PLA Poly(2-hydroxylethylmethacrylatehistidine)-g-poly-

(d,l-lactide)PLA Poly(lactic acid)PLGA Poly(L lactic-co-glycolic acid)PNA Peanut agglutininPOCM Peritoneal ovarian cancer metastasesPPEI Poly(ethylenimide)-co-poly(ethyleneglycol)-co-poly

(ethyl-enimide)PPF Porphyrin-peptide-folatePPI PolypropyleniminePPSD PEG-PAMAM-cis-aconityl-DoxorubicinPS PhotosensitizerPSMA Prostate-specific membrane antigenPSS Sodium poly(4-styrene sulfonate)PTT Photo thermal TherapyPTX PaclitaxelPVX Potato virus XQD Quantum dotQGY-7703 cells Human liver cancer cellsQUaPS Quantitative, unquenched activatable photosensitizersQucbl 7-(3-bromopropoxy)-2-quinolylmethyl chlorambucilRA Rheumatoid arthritisRCA Ricinus communis agglutintinRES Reticuloendothelial systemRFRT Recombinant ferritinRGD Cyclic arginine-glycine-aspartaterHSA Recombinant HSARITC Rhodamine B isothiocyanateRME Receptor-mediated endocytosisRT4 Human bladder transitional cancer cellsSCID Severe combined immunodeficientSFEE Supercritical Fluid Extraction of EmulsionSH-gC-dots Thiol-terminated C-dotsSJSA-1 Osteosarcoma cellSKBR3 Human breast adenocarcinoma cellsSLN Solid lipid nanoparticlesSPECT Single photon emission computed tomographySPION-TPP Superparamagnetic iron oxide nanoparticle–porphyrinSPTPP (5-N succinimidoxy- 5-oxopentyl)-triphenylphosphonium

bromide