327
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_23,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 23
Construction of Peptide-Drug Conjugates for Selective
Targeting of Malignant Tumor Cells
Eirinaios I. Vrettos and Andreas G. Tzakos
Abstract
Cancer constitutes a major threat to humanity, while its incidence and mortality rates are increasing rapidly
worldwide. To tackle cancer, numerous strategies have been exploited, including the development of peptide–drug conjugates (PDCs), which are considered an appealing approach to selectively populate malignant tumors with toxic substances. The general architecture of a PDC usually includes three parts: the
tumor-targeting peptide, the cytotoxic drug, and the biodegradable linker. Due to the fact that peptides
possess fast renal clearance, affecting the bioavailability of the PDC, a nanodrug formation concept can be
exploited to ameliorate this pitfall. Herein, we present methodologies to develop PDCs, along with certain
basic principles governing such constructs. In addition, we highlight possible problems that may appear
during the synthesis of PDCs, as also solutions to overcome them.
Key words Cancer, Drug delivery, Bioconjugates, Peptides, Peptide-drug conjugates (PDCs),
Targeted drug delivery
1 Introduction
Cancer is a rapidly increasing global threat and the rate of appearance is continuously growing. The 12.7 million cancer cases and
7.6 million deaths in 2008 have mounted up to 18.1 million cases
and 9.6 million deaths in 2018 [1, 2]. The most common types of
cancer are lung, breast, colorectal, and prostate, contributing to
12.3%, 12.3%, 10.6%, and 7.5% of the total number of new cases in
2018, respectively [1]. These statistics indicate that the current
therapeutics in oncology are not effective against the evolving
complexity of cancer, often due to their unspecific toxicity, reduced
solubility, permeability, and drug resistance of cancer cells.
Current cancer treatments usually include a combination of
surgery, radiation, immunotherapy, and chemotherapy.
Chemotherapeutic drugs utilized for this purpose are toxic in order
to kill cancer cells, inevitably affecting the healthy cells and there-
Thomas Mavromoustakos et al. (eds.), Supramolecules in Drug Discovery and Drug Delivery: Methods and Protocols,
Methods in Molecular Biology, vol. 2207, https://doi.org/10.1007/978-1-0716-0920-0_23,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
Chapter 23
Construction of Peptide-Drug Conjugates for Selective
Targeting of Malignant Tumor Cells
Eirinaios I. Vrettos and Andreas G. Tzakos
Abstract
Cancer constitutes a major threat to humanity, while its incidence and mortality rates are increasing rapidly
worldwide. To tackle cancer, numerous strategies have been exploited, including the development of peptide–drug conjugates (PDCs), which are considered an appealing approach to selectively populate malignant tumors with toxic substances. The general architecture of a PDC usually includes three parts: the
tumor-targeting peptide, the cytotoxic drug, and the biodegradable linker. Due to the fact that peptides
possess fast renal clearance, affecting the bioavailability of the PDC, a nanodrug formation concept can be
exploited to ameliorate this pitfall. Herein, we present methodologies to develop PDCs, along with certain
basic principles governing such constructs. In addition, we highlight possible problems that may appear
during the synthesis of PDCs, as also solutions to overcome them.
Key words Cancer, Drug delivery, Bioconjugates, Peptides, Peptide-drug conjugates (PDCs),
Targeted drug delivery
1 Introduction
Cancer is a rapidly increasing global threat and the rate of appearance is continuously growing. The 12.7 million cancer cases and
7.6 million deaths in 2008 have mounted up to 18.1 million cases
and 9.6 million deaths in 2018 [1, 2]. The most common types of
cancer are lung, breast, colorectal, and prostate, contributing to
12.3%, 12.3%, 10.6%, and 7.5% of the total number of new cases in
2018, respectively [1]. These statistics indicate that the current
therapeutics in oncology are not effective against the evolving
complexity of cancer, often due to their unspecific toxicity, reduced
solubility, permeability, and drug resistance of cancer cells.
Current cancer treatments usually include a combination of
surgery, radiation, immunotherapy, and chemotherapy.
Chemotherapeutic drugs utilized for this purpose are toxic in order
to kill cancer cells, inevitably affecting the healthy cells and there-