Aptamers Engineered Nanocarriers for Cancer Therapy

Aptamers Engineered Nanocarriers for Cancer TherapyEdited byPrashant KesharwaniAssistant Professor, Department of Pharmaceu ...
Copyright
Contributors
1. Cell-SELEX technology for aptamer selection
1.1 Introduction
1.2 Cell-SELEX technology
1.2.1 Challenges associated with the technique
1.2.2 Advantages and limitation associated with technique
1.3 Various cell-SELEX methods
1.4 Aptamers generated by cell-SELEX technology
1.4.1 FACS-SELEX
1.4.2 TECS-SELEX
1.4.3 3D cell-SELEX
1.4.4 Cell-internalization SELEX
1.4.5 Hybrid-SELEX
1.5 Cell-SELEX technique for aptamer selection development and applications
1.6 Conclusion
Acknowledgment
References
2. Aptamers in biosensing: biological characteristics and applications
2.1 Introduction
2.2 Biochemical characteristics of aptamers exploited for biosensing
2.2.1 Structure-switching method
2.2.2 Enzyme-assisted recycling method
2.2.3 Split aptamer-based method
2.3 Aptamer-based biosensing systems for the detection of exosomes
2.4 Aptamer-based intracellular biosensing
2.4.1 Aptamers as direct therapeutics for cancer
2.4.2 Aptamers as direct therapeutics for other diseases
2.4.3 Aptamer-drug conjugate systems for targeted therapy
2.4.4 Aptamers for intracellular biosensing
2.4.5 Aptamer-nanomaterial conjugated systems for intracellular biosensing and drug delivery
2.5 Conclusions
References
3. Mechanisms of multidrug resistance in cancer
3.1 Introduction
3.1.1 The role of drug transporters in cancer MDR
3.1.1.1 P-glycoprotein transporter and MDR
3.1.1.2 BCRP transporter and MDR
3.1.1.3 MRP1 transporter and MDR
3.1.1.4 LRP/MVP transporter and MDR
3.1.2 The role of signaling pathways in cancer MDR
3.1.2.1 ERK signaling pathway and MDR
3.1.2.2 PI3K/Akt signaling pathway and MDR
3.1.2.3 NF-кB signaling pathway and MDR
3.1.2.4 mTOR signaling pathway and MDR
3.1.2.5 EGFR signaling pathway and MDR
3.1.3 The role of autophagy in cancer MDR
3.1.4 The role of EMT in cancer MDR
3.1.5 The role of cell cycle events in cancer MDR
3.1.6 The role of apoptosis in cancer MDR
3.1.6.1 p53 and MDR
3.1.6.2 Bcl-2 family and MDR
3.1.7 The role of DNA repair mechanisms in cancer MDR
3.1.8 The role of microRNAs (miRNAs) in cancer MDR
3.1.9 The role of inflammation and growth factors in cancer MDR
3.1.10 The role of cancer stem cells in cancer MDR
3.1.11 The role of exosomes in cancer MDR
3.1.12 Drug inactivation and cancer MDR
3.2 Alterations in drug targets and decreased drug uptake and cancer MDR
3.3 Conclusion
Competing interests
References
4. Relevance of aptamers as targeting ligands for anticancer therapies
4.1 Introduction
4.1.1 As1411 aptamer (AGRO001)
4.1.2 Sgc8-c aptamer
4.1.3 NOX-A12 (Olaptesed pegol)
4.1.4 NAS-24
4.1.5 CD44 aptamer
4.1.6 EpCAM aptamer
4.1.7 Anti-PD–L1 aptamer
4.1.8 MUC-1 aptamer
4.1.9 Forkhead Box M1 (FOXM1)
4.1.10 PSMA aptamer
4.1.11 HPV E6/E7 aptamers
4.2 Conclusion
References
5. Aptamers as smart ligands for the development of cancer-targeting nanocarriers
5.1 Introduction
5.2 Selection of Aps
5.3 Recent advances in aptamer selection technology
5.4 Diagnostic applications of Aps
5.5 Therapeutic applications of aptamers
5.5.1 Ap-conjugated NPs
5.5.2 Hybrid Ap-based structures
5.5.3 Bispecific Aps with antitumor immunity function
5.5.4 Ap-based multimodal NSs
5.6 Concluding remarks
References
6. Aptamer-functionalized liposomes for targeted cancer therapy
6.1 Introduction
6.2 Conjugation strategies in aptamer-targeted liposomes
6.2.1 Membrane anchor method (pre-conjugation strategy)
6.2.2 Postinsertion method
6.3 Factors affecting the efficiency of aptamer-functionalized liposomes
6.3.1 Conjugation chemistry of aptamers and liposomes
6.3.2 The spacer structure
6.3.3 Aptamer characteristics
6.3.4 Surface density of aptamers
6.4 Aptamer-mediated targeted delivery of liposomes
6.4.1 Protein tyrosine kinase 7 (PTK7)
6.4.2 E-selectin
6.4.3 CD44 protein
6.4.4 Prostate-specific membrane antigen
6.4.5 Nucleolin protein
6.4.6 Transferrin receptor
6.4.7 Epidermal growth factor receptor (EGFR)
6.4.8 Epithelial cell adhesion molecule (EpCAM)
6.4.9 Endoglin (ENG)
6.4.10 Others
6.5 Future perspectives and conclusion
References
7. Aptamer-functionalized micelles for targeted cancer therapy
7.1 Targeting
7.1.1 Aptamer
7.1.2 SELEX
7.1.3 Aptamer internalization mechanisms
7.2 Aptamer-functionalized micelles
7.2.1 Micelles
7.2.2 Apt-micelles
7.2.3 Apt-micelles in cancer treatment
7.3 Conclusion
References
8. Aptamer-functionalized nanoparticles for targeted cancer therapy
8.1 Introduction
8.2 Preparations of different aptamer-functionalized nanoparticles
8.2.1 Aptamer-functionalized Au nanoparticles
8.2.2 Aptamer-functionalized liposome nanoparticles
8.2.3 Aptamer-functionalized polymeric nanoparticles
8.2.4 Aptamer-functionalized hybrid nanoparticles
8.2.5 Aptamer-functionalized mesoporous silica nanoparticles
8.3 Applications of aptamer-functionalized nanoparticles
8.3.1 Biosensors to detect cancerous cells
8.3.2 Targeted drug delivery and cancer therapy
8.3.3 Targeted photodynamic therapy
8.3.4 Thermo-chemotherapy
8.3.5 Other applications besides cancer therapy
8.4 Conclusion and future perspective
Acknowledgment
References
9. Aptamer-functionalized PLGA nanoparticles for targeted cancer therapy
9.1 Introduction
9.2 Aptamers
9.3 Role of aptamers in cancer therapy
9.4 PLGA and nanoparticle
9.5 PLGA nanoparticles for drug delivery to tumors
9.6 Nanoparticle surface modification with PLGA
References
10. Aptamer-functionalized silicon nanoparticles for targeted cancer therapy
10.1 Introduction of silicon nanoparticles (SNP)
10.1.1 Mesoporous SNP (MSNs)
10.1.2 Conventional nonporous SNP
10.1.3 Hollow mesoporous silica nanoparticle (HMSN)
10.1.4 Core-shell SNP
10.2 Biomedical applications of SNP
10.2.1 Drug delivery
10.2.2 Imaging
10.2.3 Photodynamic therapy (PDT)
10.2.4 Photothermal therapy (PTT) technique
10.3 SNP for cancer therapy
10.4 Aptamer-conjugated SNP
10.5 Biocompatibility and toxicity of SNP
10.6 Conclusions
References
11. Aptamer-functionalized dendrimers for targeted cancer therapy
11.1 Introduction
11.2 Dendrimer as emerging tool in targeted therapy against cancer
11.3 Extending the dimension of aptamer functionalized dendrimer-based cancer therapy
11.4 The revolution of aptamer-grafted dendrimer as gene therapy against cancer cells
11.5 Conclusion
References
12. Aptamer-conjugated carbon nanotubes or graphene for targeted cancer therapy and diagnosis
12.1 Introduction
12.2 Carbon nanostructures and their biomedical applications
12.3 Aptamer decorated carbon nanotubes (CNTs) or graphene for targeted cancer therapy
12.3.1 CNTs
12.3.2 Graphene
12.4 Aptamer decorated CNTs and graphene: biosensing potentials
12.4.1 CNTs
12.4.2 Graphene
12.5 Conclusion, challenges, and future prospective
References
13. Aptamer-functionalized quantum dots for targeted cancer therapy
13.1 Cancer therapy methods
13.2 Aptamers in targeted cancer therapy
13.3 SELEX
13.3.1 Quantum dot-aptamer (QD-Apt) conjugate in targeted cancer treatment
References
14. Cancer immunotherapy via nucleic acid aptamers
14.1 Introduction
14.2 SELEX method for developing immunotherapeutic aptamers
14.3 Extracellular targets of aptamers
14.4 Aptamers targeting costimulatory molecules in cancer immunotherapy
14.4.1 PD-1
14.4.2 CTLA-4
14.4.3 CD28
14.4.4 OX40
14.4.5 4-1BB
14.4.6 CD30
14.4.7 EGFR
14.5 Aptamers targeting immunosuppressive cytokines in cancer immunotherapy
14.6 Bispecific aptamers
14.7 Aptamer-siRNA conjugates
14.8 Aptamers in adoptive cell transfer
14.9 Aptamers and targeted antigen delivery in cancer immunotherapy
14.10 Conclusion
References
Further reading
15. Recent advances in aptamer-based nanomaterials in imaging and diagnostics of cancer
15.1 Introduction
15.2 Technological selection of aptamer structure
15.2.1 Systematic evolution of ligand by exponential enrichment (SELEX)
15.2.2 Cell systematic evolution of ligands by exponential enrichment (cell-SELEX)
15.3 Aptamer in diagnosis and therapy
15.3.1 Diagnosis
15.3.2 Imaging
15.4 Nano-integration of aptamer in cancer
15.4.1 Nano-aptamer in cancer imaging in vivo
15.4.1.1 Fluorescence imaging
15.4.1.2 MRI imaging
15.4.1.3 PET/CT imaging
15.4.1.4 Single-photon emission computed tomography (SPECT) imaging
15.4.2 Aptamer in cancer diagnosis
15.4.2.1 Aptasensor
15.4.2.2 Aptamer for Circulating Tumor Cells (CTCs) detecting agent
15.4.2.3 Aptamer based colorimetric assay
15.4.2.4 Aptamer based cell sorting
15.5 Conclusions and future perspectives
References
16. Microdevice-based aptamer sensors
16.1 Introduction
16.2 Microdevices—general principles
16.3 Aptamers in microfluidic devices
16.3.1 Aptamers and in vitro selection methods
16.3.2 Immobilization of aptamers on microchips.
16.3.3 Detection techniques in microfluidic devices
16.4 Applications of microdevices with aptamers
16.4.1 Microdevice-based aptasensors for biomedical and forensic applications
16.4.2 Microdevice-based electrochemical aptasensors
16.4.3 Microdevice-based optical aptasensors
16.4.3.1 RIFTS aptasensors
16.4.3.2 Colorimetric aptasensors
16.4.3.3 Luminescence-based and fluorimetric aptasensors
16.4.4 Sample preparation for biomedical and forensic aptasensors
16.4.5 Microdevice-based aptasensors for food and environmental applications
16.4.6 Microdevice-based electrochemical aptasensors
16.4.7 Microdevice-based optical aptasensors
16.4.7.1 Colorimetric aptasensors
16.4.7.2 Fluorimetric aptasensors
16.4.7.3 Bright field imaging technique
16.4.8 Sample preparation for food and environment aptasensors
16.5 Future trends and conclusions
Acknowledgments
References
17. Aptamer-based microfluidics for circulating tumor cells
17.1 Metastasis and formation of CTCs
17.2 Aptamers as powerful tools recognizing CTCs
17.2.1 Systematic evolution of ligands by EXponential enrichment (SELEX)
17.2.1.1 High-throughput-based SELEX
17.2.1.2 Cell-based SELEX
17.2.1.3 Microfluidic SELEX
17.3 Aptamer-based microfluidics for CTC isolation and capture
17.4 Aptamer-based microfluidics for CTCs release and analysis
17.4.1 CTCs release
17.4.2 CTCs analysis
17.5 Nanotechnology-based strategies for CTCs based on microfluidic chip technologies
17.6 Conclusions and future perspectives
References
18. Aptamer-based theranostic approaches for treatment of cancer
18.1 Introduction
18.2 Different nano-platforms for the theranostic aim
18.2.1 Superparamagnetic iron oxide nanoparticles (SPIONs)
18.2.2 Gold nanoparticles
18.2.3 Polymer-based nanoparticles
18.2.4 Protein-based nanoparticles
18.2.5 Dendrimers
18.2.6 Mesoporous silica nanoparticles
18.2.7 Lipid-based nanoparticles
18.2.8 Other nanoparticles
18.2.9 DNA nano-platforms
18.3 Future prospect and conclusion
Acknowledgment
References
19. Challenges of aptamers as targeting ligands for anticancer therapies
19.1 Introduction
19.2 Aptamers and their properties
19.3 Synthesis of aptamers
19.3.1 Protein-based SELEX
19.3.2 Whole-cell-based SELEX
19.3.3 Multitarget SELEX
19.3.4 In vivo SELEX
19.3.5 Hybrid SELEX
19.3.6 Live- animal-based SELEX
19.3.7 Modification of aptamers
19.4 Aptamers for diagnosis and treatment of cancers
19.4.1 Aptamers in cancer diagnosis
19.4.2 Aptamers-nanoparticles conjugation strategies in cancer therapy
19.4.3 Aptamers as therapeutic agents in cancer treatment
19.4.3.1 Aptamers in breast cancer therapy
19.4.3.2 Aptamers in colorectal cancer therapy
19.4.3.3 Aptamers in lung cancer therapy
19.4.3.4 Aptamers in prostate cancer therapy
19.4.3.5 Aptamers in renal cancer therapy
19.4.3.6 Aptamers in other cancer therapy
19.5 Clinical trials on aptamers
19.6 Challenges of aptamers in anticancer therapies
19.6.1 Rapid renal excretion
19.6.2 Aptamer safety
19.6.3 Stability of aptamers
19.6.4 Aptamers as targeting molecules
19.7 Future challenges
19.8 Conclusion
References
20. Clinical use and future perspective of aptamers
20.1 Introduction
20.2 Improving aptamer efficacy
20.2.1 Modifications on oligonucleotide 3′ and 5′ terminals
20.2.1.1 Terminal 3′–3′ and/or 5′–5′ internucleotide
20.2.1.2 3′ and 5′-Biotin conjugation
20.2.1.3 Conjugation of 5′- end with cholesterol and other lipid units
20.2.1.4 PEGylation at the 5′-terminus of aptamers
20.2.2 Ribose sugar unit modification
20.2.2.1 Modifications on the 2′ position of the ribose sugar unit
20.2.2.2 Oxygen replacement of the ribose sugar unit
20.2.3 Locked and unlocked aptamers
20.2.4 Phosphodiester linkage chemical modifications
20.2.4.1 Methylphosphonate or phosphorothioate
20.2.4.2 X-aptamers
20.2.4.3 Triazole modification
20.2.5 Modifications on the nucleobases
20.2.6 The slow off-rate modified aptamers (SOMAmers)
20.2.7 Spiegelmers
20.2.8 Circular aptamers (CAs)
20.2.9 Aptamers merging (multivalent)
20.2.10 Aptamers toxicity and immunogenicity
20.3 Preclinical and clinical trials of aptamers
20.3.1 Aptamers in coagulation
20.3.2 Aptamers in diabetes
20.3.3 Aptamers in cancer
20.3.4 Aptamers in infectious diseases
20.4 Aptamers in clinical studies and clinical use
20.4.1 Aptamers from clinical studies to clinical use for age related macular degenerative disease
20.4.1.1 Aptamer targeting vascular endothelial growth factor (VEGF)
20.4.1.2 Aptamer targeting the Platelet Derived Growth Factor (PDGF)
20.4.1.3 Aptamer targeting the complement system
20.4.2 Aptamer clinical studies for coagulation therapy
20.4.2.1 Aptamer as selective anti -IXa (FIXa) coagulation factor
20.4.2.2 Aptamer binds specifically to the A1 domain of von willebrand factor (VEF)
20.4.2.3 Aptamer as an antithrombin
20.5 Conclusions and future perspectives
References
Index
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