Lanthanide Doped Magnetic Nanoparticles As Anticancer Drug Carriers

By Kiruthiga K

Cancer is a deadly disease. It remains as leading cause of death in every country of the  world  
.  Cancer  is  the  first  or  second  leading  cause  of  death among people 
of age above 70 years in 295 countries, according to the recent report by World Health Organization 
(WHO).  As the number of deaths due  to  cancer  enhances,  it  has  partial  
reflections  on  the  mortality  rates  caused  by other diseases like stroke and coronary heart 
disease. . In general, the  cancer  incidence  and  the  mortality  are  
alarmingly  increasing.  In  2020,  an estimated  19.3  million  new  cases  and  10  million  
deaths  due  to  cancer  have  been reported worldwide.

 

As of 2020, one-half of all cases and about 58.3% of cancer deaths, among men and women combined, 
occur in Asia, 22.8% in Europe, and 20.9% in America.   About  2.26  million,  
accounting  for  11.7%  of   all  sites  of  cancer,  new breast   cancer   cases   are   reported  
 at   GLOBCON   2020,   in   comparison   with GLOBOCON  2018.   Female  
breast  cancer  occupies  the  top position  in  terms  of  new  cases,  among  a  number  of  
types  of  cancers.  Cancer  was once   considered   as   a   disease   of   the   westernized   
and   industrialized   countries. Nevertheless, it has emerged as a common disease of developing 
and low-resource countries too.

 

About  5–10%  of  breast  cancer  patients  possess  a  predisposition  for  cancer  due  to 
genetic origins. Nevertheless, individuals carry genes that are susceptible to mutation
possess a higher risk of developing breast cancer than the other general population.

Most breast cancers are observed in the ductal region (80%) and the remaining 20% originate  in  
the  lobules  of  the  breast.  (Barzaman  et  al.,  2020).  Breast  cancer  is categorized  into  
three  classes:  (i)  the  one  that  expresses  an  estrogen   hormone receptor  (ER⁺)  or  a  
progesterone  receptor  (PR⁺),  (ii)  the  one  that  expresses  human epidermal receptor 2 (HER 
2⁺), and (iii) triple negative breast cancer (TNBC) (ER⁻, PR⁻,  HER2⁻)  
 

• Language: English
• Publisher: MOHAMMED ABDUL SATTAR
• Release date: Aug 11, 2023
• ISBN: 9798223557517

Book preview

Lanthanide Doped Magnetic Nanoparticles As Anticancer Drug Carriers

Kiruthiga K

TABLE OF CONTENTS

COMPLEXITY

1.3  TARGETED DELIVERY OF 3

CHEMOTHERAPEUTIC DRUGS

1.4  NANOPARTICLES AS CARRIERS: 4

THE DESIGN PRINCIPLES

1.4.1  Size 4

1.4.2  Surface properties 5

1.5  ACTIVE TARGETING USING FOLATE 5

LIGANDS

1.6  CYCLODEXTRINS IN DRUG DELIVERY 6

1.7  MAGNETIC NANOPARTICLES IN DRUG 7

DELIVERY

1.9 MCF-7 CELL LINES AS A MODEL CULTURE 11

FOR THE IN VITRO ANTICANCER STUDIES

2  REVIEW OF LITERATURE 13

2.1  LANTHANIDE CONTAINING MAGNETIC 13

NANOPARTICLES

2.2  HYDROXYAPATITE CONTAINING DOPED 17

MAGNETIC ELEMENTS

2.3  HYDROXYAPATITE CONTAINING DOPED 19

LANTHANIDE ELEMENTS

2.4  PLGA AND PEG IN COMBINATION WITH CD 19

2.5  RESEARCH GAP 21

2.6  OBJECTIVES OF THE CURRENT RESEARCH 22

WORK

3  MATERIALS AND METHODS

3.1  MATERIALS 23

3.2  METHODS 23

3.2.1  Preparation of ferrite NPs 23

3.2.2  Preparation of ferrite doped hydroxyapatite NPs 24

3.2.3  Preparation of 6-O-monotosyl-β-cyclodextrin 24

(Ts-CD)

3.2.4  Preparation of mono-6-deoxy-6- 24

aminoethylamino-β- cyclodextrin

3.2.5  Preparation of PLGA-OTs 24

3.2.6  Preparation of PLGA-β-CD conjugate 25

3.2.7  Preparation of PLGA-β-CD-folate conjugate 25

3.2.8  Synthesis of CD-PEG conjugate 25

3.2.9  β-Cyclodextrin-PEG-folate conjugate (CD- 25

PEG-fol)

3.2.10  Polymer coating of NPs 26

3.2.11  Instrumental methods 26

3.2.12  Camptothecin–loading and encapsulation 26

efficiency

3.2.13  In vitro CPT release 27

3.3  IN VITRO STUDIES ON CELL LINES 27

3.3.1  Cell culture maintenance 27

3.3.2  MTT assay 28

3.3.3  Statistical analysis 29

4  RESULT AND DISCUSSION

4.1  β-CYCLODEXTRIN - FOLATE 30

FUNCTIONALIZED POLY(LACTIC-CO- GLYCOLIDE) SUPER PARAMAGNETIC YTTERBIUM FERRITE HYBRID NANOPARTICLES

4.1.1  Synthesis and characterization of β-CD and 30

30 β-CD-folate conjugated PLGA

4.1.2  Synthesis and characterization of ytterbium 33

ferrite

4.1.3  Magnetic property of the YF NPs 43

4.1.4  Release profiles of CPT from the magnetic 44

Nanocarriers

4.1.5  Effect of CPT-loaded nanocarriers on breast 46

cancer cells

4.2  HOLMIUM FERRITE NANOPARTICLE- 52

CYCLODEXTRIN-POLYETHYLENE GLYCOL HYBRID NANOCARRIERS

4.2.1  β-CD-PEG conjugate 52

4.2.2  Holmium ferrite nanoparticles 53

4.2.3  Magnetic properties of HoFer-CD-PEG NPs 61

4.2.4  Drug loading on the HoFer-CD-PEG NPs 62

and the release of drug

4.2.5  Cell viability assay 63

4.2.6  β-CD-PEG-folate conjugate 69

4.2.7  Characterization of CD-PEG-fol coated Ho Fer 72

NPs

4.2.8  Magnetic property of CD-PEG-fol-coated 76

HoFerNPs

4.2.9  Drug loading and release 77

4.2.10  Cell viability assay 78

4.3  DESIGNED POLY(ETHYLENE GLYCOL) 83

CONJUGATE-ERBIUM DOPED MAGNETIC NANOPARTICLE HYBRID CARRIER

4.3.1  Synthesis and characterization of nanoparticles 83

4.3.2  Magnetic Property 89

4.3.3  Drug loading and release 91

4.3.4  In vitro anticancer activity 93

4.4. β-CYCLODEXTRIN-POLY(ETHYLENE 98

GLYCOL)-FOLATECONJUGATE-COATED YTTERBIUMFERRITE-HYDROXYAPATITE COMPOSITE NANOPARTICLES

4.4.1  Characterization  of  polymer-coated  Yb-Fer- 98

HAp NPs

4.4.2  Magnetic characteristics of Yb-Fer-HAp NPs 108

4.4.3  Drug release from the Yb-Fer-HAp NPs 110

4.4.4  In vitro anticancer activity 112

4.5 β-CYCLODEXTRIN-POLY(ETHYLENE GLYCOL)- FOLATE CONJUGATE-COATED HOLMIUM FERRITE HYDROXYAPATITE COMPOSITE NANOPARTICLES

116

4.5.1  Characterization of Ho-Fer-HAp NPs 116

4.5.2  Magnetic properties of Ho-Fer-HAp NPs 126

4.5.3  Drug release from the Ho-Fer-HAp NPs 128

4.5.4  In vitro cytotoxicity of CPT-loaded NPs 129

4.6 β-CYCLODEXTRIN-POLY(ETHYLENE GLYCOL)-FOLATECONJUGATE-COATED

ERBIUFERRITE HYDROXYAPATITE COMPOSITE NANOPARTICLES

133

4.6.1  Characterization of Er-Fer-HAp NPs 134

4.6.2  Magnetic property of Er-Fer-HAp NPs 143

4.6.3  Loading and release of CPT 145

4.6.4  In vitro anticancer activity 146

5  SUMMARY

6  FUTURE DIRECTIONS

REFERENCES

151

152

154

LIST OF FIGURES

4.2.1  X-Ray diffraction pattern of HoFer-CD-PEG NPs. 54

4.2.2  EDX spectrum of as-prepared HoFer NPs 55

4.2.3  Thermogravimetric profile of HoFer-CD-PEG NPs. 56

4.2.4  X-Ray photoelectron spectra of HoFer-CD-PEG NPs. 59

4.2.5  FT-IR spectra of as-prepared and polymer-coated 60

HoFer NPs.

4.2.6  Magnetization  vs.  field  curves  of  as-prepared  and 61

polymer-coated HoFer NPs.

4.2.7  Cumulative release of CPT from the HoFer-CD-PEG 62

NPs at different pH's.

4.2.8  Graphical representation of the HoFer-CD-PEG NPs and 69

the loading of CPT.

4.2.9  FT-IR spectrum of CD-PEG-fol. 71

4.2.10  Proton NMR spectrum of CD-PEG-fol. 72

4.2.11  X-ray diffraction pattern of CD-PEG-fol-coated 73

HoFer NPs.

4.2.12  FT-IR spectrum of CD-PEG-fol-coated HoFer NPs 75

4.2.13  TGA of CD-PEG-fol-coated HoFer NPs. 76

4.2.14  Magnetization vs. field curves of as-synthesized and 77 CD-PEG-fol-coated HoFer NPs.

4.2.15  Cumulative release of CPT from the HoFer-CD-PEG-fol 78 NPs at different pH's.

4.2.16  Graphical representation of the HoFer-CD-PEG-fol NPs 82 and the loading of CPT.

4.3.1  XRD pattern of ErFeO3-CD-PEG-fol NPs. 84

4.3.2  IR spectrum of ErFeO3-CD-PEG-fol NPs 85

4.3.3  TG profile of ErFeO3-CD-PEG-fol NPs. 86

4.3.4  X-Ray  photoelectron  spectra  characteristic  of  the 89 individual elements (Fe, N, O, Er, and C) ErFeO3-CD-

PEG-fol NPs.

4.5.3  X-ray photoelectron spectra of the polymer coated Ho- Fer-HAp NPs showing peaks corresponding to the elements: (a) C, (b) O, (c) P, (d) N, (e) Ca, (f) Fe, and (g) Ho

124

4.5.4  FT-IR spectrum of polymer coated-Ho-Fer-HAp NPs. 125

4.5.5  TG profile of polymer coated-Ho-Fer-HAp NPs. 125

4.5.6  Room temperature magnetization curves of the as- synthesized and polymer coated-Ho-Fer-HAp NPs.

4.5.7  Plot of the magnetization vs. square of the values of field strength of the as-synthesized Ho-Fer-HAp NPs.

4.5.8  Release profiles of CPT from polymer coated Ho-Fer- HAp NPs at two different pH's.

126

127

129

4.5.9  (d) Dose-dependent cell viability depicted as histogram. 132

4.5.10  Graphical representation of polymer-coated Ho-Fer- HAp NPs and the loading of CPT.

4.6.1  X-ray diffraction pattern of polymer coated-Er-Fer- HAp NPs.

4.6.2  Particle size distribution of polymer coated-Er-Fer-HAp NPs as revealed by dynamic light scattering

4.6.3  X-Ray photoelectron spectra characteristic of the individual elements, (a) C, (b) O, (c) N, (d) Ca, (e) P, (f) Fe, and (g) Er, of polymer coated Er-Fer-HAp NPs.

133

134

136

140

4.6.4  FT-IR spectrum of polymer coated Er-Fer-HAp NPs. 141

4.6.5  Thermogravimetric profile of polymer coated Er-Fer- HAp NPs.

142

4.6.6  Room temperature magnetization curves of the as- synthesized and polymer coated-Ho-Fer-HAp NPs.

4.6.7  Plot of the magnetization vs. square of the values of field strength of the as-synthesized Er-Fer-HAp NPs.

4.6.8  Release profiles of CPT from polymer coated Er-Fer- HAp NPs at two different pH's

143

144

145

4.6.9  Dose-dependent cell viability depicted as histogram 149

4.6.10  Graphical representation of polymer-coated Er-Fer-HAp NPs and the loading of CPT.

150

LIST OF ABBREVIATIONS

CPT - Camptothecin

DLS - Dynamic light scattering

Dox - Doxorubicin

EDX - Energy Dispersive X-ray spectrometer

FA - Folic Acid

FT IR - Fourier-Transformed Infrared

HeLa - Henrietta Lacks

ICPAES -

Inductively coupled plasma atomic emission spectroscopy

MNPs - Magnetic Nanoparticles

MALDI - Matrix-assisted laser desorption/ionization

Nm - Nanometer

NMR - Nuclear Magnetic Resonance

PLGA Poly Lactic co glycolic acid

PEG Poly Ethylene Glycol

SEM - Scanning Electron Microscopy

TEM - Transmission electron microscopy

TGA - Thermogravimetric analysis

UV-Vis - Ultra Violet-Visible

VSM - Vibrating-sample mag

XRD - X-ray diffraction

XPS - X-ray photoelectron spectroscopy

β CD - Beta Cyclodextrin

CHAPTER- I INTRODUCTION

1.0  INTRODUCTION

1.1  CANCER AS A DEADLY DISEASE: AN OVERVIEW

Cancer is