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Prodrug Conjugate Strategies in Targeted Anticancer Drug Delivery Systems

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Targeted Drug Delivery : Concepts and Design

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

Chemotherapy is the mainstay in the treatment of various cancers for several decades; however, it suffers several clinical limitations. For example, anticancer drugs are often nonselective and are taken up by all forms of cells. Non-selectivity of the agents usually results in significant toxicity to normal cells, thus resulting in poor prognosis for patients. Hence, to improve the therapeutic efficacy of chemotherapy, improving the selectivity of anticancer drug is highly desired. Prodrug conjugation is one of the most beneficial strategies to enhance selectivity and efficacy of a chemotherapy drug. The classical prodrug approach is to overcome physicochemical (e.g., solubility, chemical instability) or biopharmaceutical problems (e.g., bioavailability, toxicity) associated with common anticancer drugs via a simple chemical modification. On the other hand, here we discuss targeted prodrug systems for delivering anticancer agents specifically to tumor cells, thereby sparing normal cells. This chapter focuses on various synthetic strategies in designing targeted prodrug conjugates and its rationale for cancer treatment. Various tumor-targeting ligands that are currently being explored are critically discussed.

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Abbreviations

ADCC:

Antibody-dependent cellular cytotoxicity

ADEPT:

Antibody-directed enzyme prodrug therapy

AuNP:

Gold nanoparticles

BCR:

Breakpoint cluster region protein

BTK:

Bruton’s tyrosine kinase

CDK inhibitor:

Cyclin-dependent kinase inhibitors

CLL:

Chronic lymphocytic leukemia

CPT:

Camptothecin

CTC:

Circulating tumor cells

Dox:

Doxorubicin

DTC:

Disseminated tumor cells

EGFR:

Epidermal growth factor receptor

EPR:

Enhanced permeability and retention

ERK:

Extracellular signal-regulated kinases

FISH:

Fluorescence in-situ hybridization

FOL:

Folic acid

FR:

Folate Receptor

GDEPT:

Gene-directed enzyme prodrug therapy

GnRH:

Gonadotropin-releasing hormone

GRP78:

Glucose-regulated protein 78

HCC:

Hepatocellular carcinoma

HER2:

human epidermal growth factor 2

HPLC:

High-performance liquid chromatography

IGFR:

Insulin-like growth factor receptor

KRAS:

Kirsten rat sarcoma

LHRH:

Luteinizing hormone releasing hormone

mAb:

Monoclonal antibodies

MAPK:

Mitogen-activated protein kinases

MCL:

Mantle cell lymphoma

mCRC:

Metastatic colorectal cancer

MDNS:

Magneto-Dendritic Nano System

MDR:

Multiple-drug resistance

mRNA:

Messenger ribonucleic acid

mTOR:

Mammalian target of rapamycin

NSCLC:

Non-small-cell lung cancer

PCR:

Polymerase chain reaction

PDGFRβ:

Platelet-derived growth factor receptor

PI3K:

Phosphatidylinositol 3-kinase

PIGF:

Placental growth factor

RCC:

Renal cell carcinoma

RET:

Rearranged during transfection

RGD:

Arginine-glycine-aspartic acid

SCCHN:

Squamous cell carcinoma of the head and neck

scFv:

Single chain variable fragment

siRNA:

Small interfering RNA

Tf:

Transferrin

Tf-PEG-AD:

Transferrin-conjugated poly (ethylene glycol)-adamantane

TfR:

Transferrin receptor

TPGS:

D-α-Tocopheryl polyethylene glycol succinate

US FDA:

United States Food and Drug administration

VEGF:

Vascular endothelial growth factor

VEGFR:

Vascular endothelial growth factor receptor

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Authors and Affiliations

  1. Actorius Innovations and Research (AIR), Pune, India

    Shashwat Banerjee & Kiran Todkar

  2. Maharashtra Institute of Pharmacy, MIT Campus, Kothrud, Pune, India

    Govind Chate & Jayant Khandare

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  1. Shashwat Banerjee
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  2. Kiran Todkar
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  3. Govind Chate
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  4. Jayant Khandare
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Corresponding author

Correspondence to Jayant Khandare .

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Editors and Affiliations

  1. Institute of Chemical Technology, Department of Pharmaceutical Sciences and Technology, Mumbai, India

    Padma V. Devarajan

  2. National Institute of Pharmaceutical Education and Research (NIPER), Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, Mohali, Punjab, India

    Sanyog Jain

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© 2015 Controlled Release Society

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Banerjee, S., Todkar, K., Chate, G., Khandare, J. (2015). Prodrug Conjugate Strategies in Targeted Anticancer Drug Delivery Systems. In: Devarajan, P., Jain, S. (eds) Targeted Drug Delivery : Concepts and Design. Advances in Delivery Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-11355-5_11

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