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Transferrin Receptor and Targeting Strategies

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Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 39))

Abstract

Treatment of cancer is an extraordinary challenge using conventional therapy due to serious side effects. Targeted delivery of therapeutics has changed this paradigm. Among various approaches, receptor-mediated targeting presents great promise. Since transferrin receptor (TfR) is known to be overarticulated in various cancers, it is a lucrative target in cancer research. TfR-mediated drug delivery can deliver therapeutic cargo into tumor cells to enhance cytotoxicity with significant reduction in systemic toxicity. This has propelled the exploration of innovative targeting approaches using nanodrug delivery systems. This chapter discusses the TfR physiology and related pathophysiology, and also summarizes various drug-targeting strategies and theranostics, which rely on transferrin (Tf) as the targeting ligand for cell-directed delivery. Further forays into evaluating TfR-mediated targeting as a strategy to tackle brain infections are also proposed.

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Abbreviations

AL:

Acute leukemia

ALL:

Acute lymphoblastic leukemia

CMC:

Critical micelle concentration

Copper sulfate:

CuS

DA:

Dodecylamine

DAB:

Diaminobutyric poly(propylene imine)

Fe-Tf:

Iron-carrier protein transferrin

HFE:

Hereditary hemochromatosis protein

H-ferritin:

Ferritin-H homopolymer

HIF:

Hypoxia-inducible factors

hLf:

Human lactoferrin

HRE:

Hypoxia-responsive elements

hTf:

Human serum transferrin

hTF/2N:

Human serum transferrin

IgG1:

Antihuman TfR antibody

IgG1:

Monoclonal antibody 454A12 P

IgG1:

Monoclonal antibody 5E9

IgG1:

Monoclonal antibody HB21

IgG3:

Chimeric human TfR antibody fused

IRE:

Iron-responsive elements

IRP:

Iron regulatory proteins

MrTf:

Rabbit serum transferrin

MTF:

Melanotransferrin

mTOR:

Mammalian target of rapamycin

NIR:

Near-infrared

NLCs:

Nanostructured lipid carriers

oTf:

Chicken ovotransferrin

PEG:

Polyethylene glycol

PEG-PE:

Polyethylene glycol-phosphatidylethanolamine

PHD:

Prolyl hydroxylases

Reg1:

Regnase-1

RGD:

Arginine–glycine–aspartic acid

ROS:

Reactive oxygen species

SA:

Stearylamine

SLNs:

Solid lipid nanoparticles

SP:

Spermine

Tf:

Transferrin

TfR:

Transferrin receptor

TfR1:

Transferrin receptor 1

TfR2:

Transferrin receptor 2

TPGS-COOH:

D-α-tocopheryl polyethylene glycol 1000 succinate

TTP:

Tristetraprolin

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Author notes

  1. Harsh A. Joshi and Esha S. Attar are contributed equally to this work.

Authors and Affiliations

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

    Harsh A. Joshi & Esha S. Attar

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence, Government of Maharashtra, Mumbai, India

    Prajakta Dandekar & Padma V. Devarajan

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  1. Harsh A. Joshi
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  2. Esha S. Attar
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  3. Prajakta Dandekar
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  4. Padma V. Devarajan
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Correspondence to Padma V. Devarajan .

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  1. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Padma V. Devarajan

  2. Department of Pharmaceutical Sciences, Insitute of Chemical Technology Deemed University, Elite Status and Centre of Excellence Government of Maharashtra, Mumbai, India

    Prajakta Dandekar

  3. Piramal Enterprises Limited, Pharmaceutical R&D, Mumbai, India

    Anisha A. D'Souza

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Joshi, H.A., Attar, E.S., Dandekar, P., Devarajan, P.V. (2019). Transferrin Receptor and Targeting Strategies. In: Devarajan, P., Dandekar, P., D'Souza, A. (eds) Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis. AAPS Advances in the Pharmaceutical Sciences Series, vol 39. Springer, Cham. https://doi.org/10.1007/978-3-030-29168-6_16

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