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Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents

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Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. Its poor response to current treatment options in advanced stages and the need for efficient diagnosis in early stages call for the development of new therapeutic and diagnostic strategies. Some of them are based on the use of nanometric materials as carriers and releasers of therapeutic agents and fluorescent molecules, or even on the utilization of magnetic materials that provide very interesting properties. These nanoformulations present several advantages compared with the free molecular cargo, including increased drug solubility, bioavailability, stability, and tumor specificity. Moreover, tumor multidrug resistance has been decreased in some cases, leading to improved treatment effectiveness by reducing drug dose and potential side effects. Here, we present an updated overview of the latest advances in clinical research, in vivo studies, and patents regarding the application of nanoformulations in the treatment of CRC. Based on the information gathered, a wide variety of nanomaterials are being investigated in clinical research, even in advanced phases, i.e., close to reaching the market. In sum, these novel materials can offer remarkable advantages with respect to current therapies, which could be complemented or even replaced by these nanosystems in the near future.

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Abbreviations

5-FU:

5-Fluorouracil

FOLFIRI:

5-FU/LV/IRI

FOLFIRINOX:

5-FU/LV/IRI/OXA

FOLFOX:

5-FU/LV/OXA

HCPT:

10-Hydroxycamptothecin

Apt:

Aptamer

AD:

Arginine deiminase

BC:

Breast cancer

BCRP:

Breast cancer resistance protein

CAP:

Capecitabine

CRT:

Chemoradiotherapy

CRC:

Colorectal cancer

TPGS:

d-α-Tocopherol polyethylene glycol 1000 succinate

DPD:

Dihydropyrimidine dehydrogenase

DOX:

Doxorubicin

EGFR:

Epidermal growth factor receptor

EpCAM:

Epithelial cell adhesion molecule

FUPEP:

FOLFIRI and PEP02

GR:

Glutathione reductase

HNM:

Head and neck melanoma

HT:

Hyperthermia

IRI:

Irinotecan

LV or FOL:

Leucovorin or folinic acid

LC:

Lung cancer

MDR:

Multidrug resistance

NPs:

Nanoparticles

OXA:

Oxaliplatin

PGP:

P-glycoprotein

PEDF:

Pigment epithelium-derived factor

PEG:

Poly (ethylene glycol)

PEI:

Polyetherimide

C225-PCQD:

Porphyrin carbon quantum dots conjugated with cetuximab

PTT:

Photothermal therapy

anti-PDL1:

Programmed cell death-1 ligand-1 antibody

PCFT:

Proton-coupled folate transporter

RT:

Radiotherapy

RFC-1:

Reduced folate transporter 1

shRNA:

Short hairpin RNA molecule

SECs:

Sinusoidal endothelial cells

SPIONs:

Superparamagnetic iron oxide nanoparticles

TS:

Thymidylate synthase

Tfr:

Transferrin

TPP:

Triphenylphosphonium

TDP1:

Tyrosyl-DNA phosphodiesterase 1

UGT:

UDP-glucuronosyltransferases

VEGFR:

Vascular endothelial growth factor receptor

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Funding

This work was funded by the Consejería de Salud de la Junta de Andalucía (PI-0102-2017) and by the Group CTS-107. This work was also partially supported by a grant from the Instituto de Salud Carlos III (ISCIII) (PI19/01478) (FEDER).

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  1. CM and ARR are co-senior authors and have contributed equally to this work.

Authors and Affiliations

  1. Institute of Biopathology and Regenerative Medicine IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100, Granada, Spain

    Laura Cabeza, Gloria Perazzoli, Cristina Mesas, Cristina Jiménez-Luna, José Prados & Consolación Melguizo

  2. Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071, Granada, Spain

    Laura Cabeza, Cristina Mesas, José Prados & Consolación Melguizo

  3. Instituto de Investigación Biosanitaria ibs. GRANADA, 18012, Granada, Spain

    Laura Cabeza, Gloria Perazzoli, Cristina Mesas, José Prados & Consolación Melguizo

  4. Department of Oncology, Ludwig Institute for Cancer Research, University of Lausanne, 1066, Epalinges, Switzerland

    Cristina Jiménez-Luna

  5. Department of Health Science, University of Jaén, 23071, Jaén, Spain

    Ana Rosa Rama

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  1. Laura Cabeza
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Correspondence to José Prados.

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Cabeza, L., Perazzoli, G., Mesas, C. et al. Nanoparticles in Colorectal Cancer Therapy: Latest In Vivo Assays, Clinical Trials, and Patents. AAPS PharmSciTech 21, 178 (2020). https://doi.org/10.1208/s12249-020-01731-y

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