https://orcid.org/0000-0001-8928-3681
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ABSTRACT
Introduction
The use of nanoparticles for breast cancer targeting and treatment has become a reality. They are safe and possess interesting peculiarities such as the unspecific accumulation into the tumor site and the possibility to activate controlled drug release as compared to free drugs. However, there are still many areas of improvement which can certainly be addressed with the use of peptide-based elements.
Areas covered
The article reviews different preclinical strategies employing peptides and proteins in combination with nanoparticles for breast cancer targeting and treatment as well as peptide and protein-targeted encapsulated drugs, and it lists the current clinical status of therapies using peptides and proteins for breast cancer.
Expert opinion
The conjugation of protein and peptides can improve tumor homing of nanoparticles, increase cellular penetration and attack specific drivers and vulnerabilities of the breast cancer cell to promote tumor cytotoxicity while reducing secondary effects in healthy tissues. Examples are the use of antibodies, arginylglycylaspartic acid (RGD) peptides, membrane disruptive peptides, interference peptides, and peptide vaccines. Although their implementation in the clinic has been relatively slow up to now, we anticipate great progress in the field which will translate into more efficacious and selective nanotherapies for breast cancer.
Abbreviations
| αvβ3 | = | Alpha-v beta-3 integrin |
| αvβ6 | = | Alpha-v beta 6 integrin |
| AML | = | Monophosphoryl lipid A |
| BC/s | = | Breast cancer/s |
| CXCR4 | = | Chemokine receptor type 4 |
| CPP | = | Cell penetration peptide |
| DOPE | = | Dioleoylphosphatidylethanolamine |
| ECM | = | Extracellular matrix |
| EGFR | = | Epidermal growth factor receptor |
| EGFR+ | = | Epidermal growth factor receptor positive |
| EphA2 | = | Ephrin receptor A2 |
| EPR | = | Enhanced permeability and retention effect |
| ER | = | Estrogen receptor |
| Fab | = | Fragment antigen binding |
| FDA | = | Food and Drug Administration |
| FITC | = | Fluorescein isothiocyanate |
| Fv | = | Fragment variable |
| HER2 | = | Human epidermal growth factor receptor 2 |
| HER2+ | = | Human epidermal growth factor receptor 2 positive |
| IC50 | = | Half maximal inhibitory concentration |
| MMP-2 | = | Metalloproteinase-2 |
| MMP-9 | = | Metalloproteinase-9 |
| Mn | = | Manganese |
| MRI | = | Magnetic resonance imaging |
| NP/s | = | Nanoparticle/s |
| PEG | = | Polyethylene glycol |
| PD-L1 | = | Programmed death-ligand 1 |
| PGMA | = | Poly(glycidyl) methacrylate |
| PLGA | = | Poly(lactic-co-glycolic acid |
| PR | = | Progesterone receptor |
| RGD | = | Arginylglycylaspartic acid |
| ROS | = | Reactive oxygen species |
| siRNA | = | Small interfering ribonucleic acid |
| SV40 | = | Simian virus 40 |
| TNBC/s | = | Triple negative breast cancer/s |
| ZnS | = | Zinc sulfide |
| Zr | = | Zirconium |
| 3D | = | Tridimensional |
Article highlights
Nanotechnology has revolutionized breast cancer treatment by providing safer and targeted alternatives to free drugs and a wide range of promising therapies consisting of nanoparticles of very different nature, unfunctionalized or functionalized with protein and peptides.
Peptides represent an emerging field of research for the treatment of breast cancer. As such, they can benefit from nanotechnology to preserve their native structure, activity and stability in vivo, increase tumor homing mediated by the EPR effect, improve their penetration and tightly control their delivery in a spatio-temporal manner.
Likewise, therapeutic nanoparticles can increase their anticancer potential in breast cancer by the conjugation with peptide and protein elements such as antibodies recognizing specific breast cancer epitopes on the cell membrane, RGD peptides, membrane disturbing peptides, peptides able to inhibit oncogenic transcriptional programs and enzymes remodeling the tumor microenvironment and the metabolic pathways. Thus, the conjugation of peptides improves oncogenic target selectivity and specificity of nanoparticles containing drugs and thus increase drug efficiency while reducing systemic toxicity.
The nanoencapsulation of peptide-based vaccines derived from HER2/neu for breast cancer treatment is a novel therapeutic approach with great potential.
Although there are currently approved targeted nanoformulations for breast cancer e.g. nab-paclitaxel plus atezolizumab, there are still no approved nanoparticles incorporating specific breast tumor homing components.
Peptide and nano-technologies are still facing many challenges that halter their complete implementation in the clinical setting.
This box summarizes key points contained in the article.
Declaration of interest
A Sorolla discloses funding from Raine Medical Research Foundation, grant number RPG-004-19 and the Marie Skłodowska-Curie Individual fellowship from the European Commission, project ID 893384. V Ceña discloses funding from Spanish Ministerio de Economía y Competitividad (project SAF2017-89288-R from MINECO/AEI/FEDER/UE), from Junta de Comunidades de Castilla-La Mancha (project SBPLY/19/180501/000067), ISCIII and ERANET Euronanomed Program (project NANO4GLIO), and COST Action Nano2Clinic (CA17140), supported by COST (European Cooperation in Science and Technology). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.