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Folate Receptor and Targeting Strategies

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Book cover Targeted Intracellular Drug Delivery by Receptor Mediated Endocytosis

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

Abstract

The folate receptor (FR) is essential for intracellular transport of folic acid, a vital enzymatic cofactor required for cell survival and growth. FR exists in four isoforms termed as α, β, γ, and δ having variable affinity for folate ligand and exhibit differential expression in normal tissues. The receptors are known to amplify in a broad spectrum of cancers and therefore have been extensively explored to treat as well as to diagnose various cancers. This chapter presents an overview of the receptor family, ligands explored, pathophysiological features, importance of FR in therapeutics and diagnostics, different FR-mediated delivery systems, and clinical studies relying on FR targeting.

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Abbreviations

5-CH3-THF:

5 Methyl tetrahydrofolate

5-CHO-THF:

5-Formyltetrahydrofolate

A549:

human lung adenocarcinoma cell line

Ala:

Alanine

ALL:

Acute lymbhoblastic leukemia

AML:

Acute myelogenous leukemias

Arg:

Arginine

CD:

Clusters of differentiation

CDDP:

Cis-diamminedichloroplatinum

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myelogenous leukemias

CT:

Computed tomography

DNA:

Deoxyribonucleic acid

DPPE:

Dipalmitoyl phosphatidylethanolamine

DSPC:

1,2-Distearoyl-sn-glycero-3-phosphatidylcholine

DSPE:

1,2-Distearoylphosphatidylethanolamine

EPR effect:

Enhanced permeation and retention effect

FA:

Folic acid

FA-PEG/PEO–PPO–PCL:

Folic acid–polyethyleneglycol/polyethyleneoxide-poly(Ɛ-caprolactone)

FA-PEG-DOX:

Folic acid–polyethylene glycol–doxorubicin

FA-PEG-PLA:

Folic acid–polyethylene glycol–polylactic acid

FITC:

Fluorescein isothiocyanate

FR:

Folate receptor

Glu:

Glutamic acid

Gly:

Glycine

GPI:

Glycosyl phosphatidylinositol

HDL:

High density lipid

HeLa:

Cervical cancer cell lines

HepG2:

Hepatocellular carcinoma cell line

His:

Histidine

HT 29:

A human colorectal adenocarcinoma cell line

HT-1080:

A human fibrosarcoma cell line

HuR:

Human antigen R

IC50:

Inhibitory concentration 50

IM:

Intramuscular

JEG-3 and JAR:

Placental choriocarcinoma cell lines

KB:

Line KB is now known to be a subline of the ubiquitous KERATIN-forming tumor cell line HeLa

Leu:

Leucine

mab 343:

A monoclonal antibody to FR-α

mab 909:

A monoclonal antibody to FR-β

met:

Methionine

MKN28:

Gastric cancer cell line

MRI:

Magnetic resonance imaging

m-RNA:

Messenger RNA

NIR:

Near infra red

NLCs:

nanostructured lipid carriers

PAMAM:

Polyamidoamine

PE:

Phosphatidylethanolamine

PEG:

Polyethylene glycol

PEO–PPO–PCL:

Polyethylene oxide-polypropylene oxide-poly(Ɛ-caprolactone)

PET:

Positron emission tomography

P-gp:

P-glycoprotein

Phe:

Phenylalanine

PLGA:

Poly lactic-co-glycolic acid

Pro:

Proline

PTX:

Paclitaxel

RFC:

Reduced folate carrier

RNA:

Ribonucleic acid

Ser:

Serine

siRNA:

Small interfering RNA

SKOV3:

Ovarian cancer cell line

SLN:

Solid lipid nanoparticles

TAM:

Tumor-associated macrophages

Thr:

Threonine

Trp:

Tryptophan

Tyr:

Tyrosine

UVA:

Ultraviolet A

Val:

Valine

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  1. Bhagyashri Joshi and Sukhada S. Shevade contributed equally with all other contributors.

Authors and Affiliations

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

    Bhagyashri Joshi & Sukhada S. Shevade

  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. Bhagyashri Joshi
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  4. 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

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Joshi, B., Shevade, S.S., Dandekar, P., Devarajan, P.V. (2019). Folate 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_14

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