18 Polyethylene Glycolation (PEGylation) and the Similar . . . . . . . . . 331
Dong Soo Lee and Yun-Sang Lee
18.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
18.2 Variety of Hydrophilization of the Surface
of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
18.3 PEGylation/Zwitterion-Coating Countering Protein
Corona Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
18.4 Radiolabeling with PEGylation or Zwitterion Coating
of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
19 Excretion and Clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Hyung-Jun Im
19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
19.2 Renal Excretion of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . 348
19.2.1 Physiology of Renal Excretion . . . . . . . . . . . . . . . . . 348
19.2.2 Renal Excretion of Nanomaterials . . . . . . . . . . . . . . . 349
19.3 Opsonization and Mononuclear Phagocytic System
(MPS) Clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
19.3.1 Opsonization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
19.3.2 Interaction Between MPS and Nanoparticles . . . . . . . 356
19.4 Hepatobiliary Excretion of Nanoparticles . . . . . . . . . . . . . . . . 359
19.4.1 Anatomy and Physiology of the Liver . . . . . . . . . . . . 359
19.4.2 Hepatobiliary Excretion . . . . . . . . . . . . . . . . . . . . . . . 359
19.5 Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Part VII Immune Responses to Nanomaterials
20 Immune Response to PEGylated Nanomedicines:
Impact of IgM Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Amr S. Abu Lila and Tatsuhiro Ishida
20.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
20.2 Anti-PEG IgM Response to PEGylated Proteins . . . . . . . . . . . 372
20.3 Anti-PEG Response to PEGylated Nanocarriers . . . . . . . . . . . 373
20.4 Mechanism of the ABC Phenomenon . . . . . . . . . . . . . . . . . . . 374
20.5 Correlation Between Complement Activation
and the ABC Phenomenon . . . . . . . . . . . . . . . . . . . . . . . . . . 374
20.6 Properties of Anti-PEG Antibody Epitope . . . . . . . . . . . . . . . . 376
20.7 Anti-PEG Immunity in Humans . . . . . . . . . . . . . . . . . . . . . . . 377
20.7.1 Pre-existing Anti-PEG Antibodies
in Normal Donors . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
20.7.2 Clinical Implications of Anti-PEG Antibodies
on the Efficacy of PEGylated Therapeutics . . . . . . . . . 378
20.8 Non-antibody Mediated Hypersensitivity Reactions . . . . . . . . . 379
Contents
xvii
Dong Soo Lee and Yun-Sang Lee
18.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
18.2 Variety of Hydrophilization of the Surface
of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
18.3 PEGylation/Zwitterion-Coating Countering Protein
Corona Formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
18.4 Radiolabeling with PEGylation or Zwitterion Coating
of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 342
19 Excretion and Clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Hyung-Jun Im
19.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
19.2 Renal Excretion of Nanoparticles . . . . . . . . . . . . . . . . . . . . . . 348
19.2.1 Physiology of Renal Excretion . . . . . . . . . . . . . . . . . 348
19.2.2 Renal Excretion of Nanomaterials . . . . . . . . . . . . . . . 349
19.3 Opsonization and Mononuclear Phagocytic System
(MPS) Clearance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
19.3.1 Opsonization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
19.3.2 Interaction Between MPS and Nanoparticles . . . . . . . 356
19.4 Hepatobiliary Excretion of Nanoparticles . . . . . . . . . . . . . . . . 359
19.4.1 Anatomy and Physiology of the Liver . . . . . . . . . . . . 359
19.4.2 Hepatobiliary Excretion . . . . . . . . . . . . . . . . . . . . . . . 359
19.5 Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Part VII Immune Responses to Nanomaterials
20 Immune Response to PEGylated Nanomedicines:
Impact of IgM Response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Amr S. Abu Lila and Tatsuhiro Ishida
20.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
20.2 Anti-PEG IgM Response to PEGylated Proteins . . . . . . . . . . . 372
20.3 Anti-PEG Response to PEGylated Nanocarriers . . . . . . . . . . . 373
20.4 Mechanism of the ABC Phenomenon . . . . . . . . . . . . . . . . . . . 374
20.5 Correlation Between Complement Activation
and the ABC Phenomenon . . . . . . . . . . . . . . . . . . . . . . . . . . 374
20.6 Properties of Anti-PEG Antibody Epitope . . . . . . . . . . . . . . . . 376
20.7 Anti-PEG Immunity in Humans . . . . . . . . . . . . . . . . . . . . . . . 377
20.7.1 Pre-existing Anti-PEG Antibodies
in Normal Donors . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
20.7.2 Clinical Implications of Anti-PEG Antibodies
on the Efficacy of PEGylated Therapeutics . . . . . . . . . 378
20.8 Non-antibody Mediated Hypersensitivity Reactions . . . . . . . . . 379
Contents
xvii