Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective
Abstract
:1. Introduction
2. Cancer Membrane—Targeting Receptors
3. Tumor-Homing Peptides (THPs)—Characteristics
3.1. RGD Peptides—Characteristics
3.2. Cyclic RGD—Characteristics
3.3. iRGD—Characteristics
3.4. NGR Peptides—Characteristics
3.5. Cell-Penetrating Peptides (CPPs)—Characteristics
3.6. Machine Learning Approaches for Designing THP
4. Homing Peptides for Drug Delivery
4.1. THPs for Drug Delivery
4.2. THPs for Blood–Brain Barrier (BBB) Delivery
5. Homing Peptides for Imaging
6. Magnetic Nanoparticles as a Platform for Tumor-Homing Peptides
6.1. Methods of Preparation and Functionalization of Magnetic Nanoparticles
- -
- -
- -
- -
- Copper Catalyzed Azide Alkyne Cycloaddition (reaction of alkyne-modified MNP with azido derivative of polypeptide) [159];
- -
- Schiff base formation between a carbonyl group presented on the surface of MNP and an amino group of the THP [160].
6.2. Biomedical Application of Magnetic Nanoparticles
6.2.1. MNPs in Cancer Imaging
Imaging Method | Targeting Peptide | Nanocarrier | Advantages | Ref. |
---|---|---|---|---|
MRI | LTVSPWY | LTVSPWY-PEG-CS MNPs |
| [161] |
A54 | A54-GFP-coated MNPs |
| [151] | |
A54-Dex-PLGA/DOX/SPIO |
| [162] | ||
iRGD | iRGD-SPIO |
| [67] | |
CKAAKN | CKAAKN–HA–VES@USPIO NPs |
| [167] |
Diagnostic Method | Targeting Peptide | Nanocarrier | Advantages | Ref. |
---|---|---|---|---|
Magnetic field | YSA | MNPs-YSA peptide conjugates |
| [169] |
Whole-body imaging | CREKA | CREKA-SPIO |
| [170] |
Sensitive monitoring of the magnetic relaxation of IONPs with the use of MPS | IONPs-N/IONPs-N-P/IONPs-N-P with protease |
| [171] | |
MRI | A54 | Dex-PLGA/DOX/SPIO |
| [162] |
MRI | - | MNPs |
| [172] |
6.2.2. MNPs in Hyperthermia Treatment
Carrier | Ligand | Agent/ Tag | Tumor | Result | Ref. |
---|---|---|---|---|---|
Magneto-liposome | cRGD | DOX/ICG | In vitro: lung, breast, skin, brain, and liver cancer In vivo: BALB/c mice murine immuno-competent fibrosarcoma tumor model | Combinatorial tumor therapy (chemo-radio-hyperthermia) Insignificant cardiac toxicity | [179] |
Fe3O4@PMAO-PEG | RGD | ND | In vitro compatibility assay: Vero cells | Prototype system for further in vivo evaluation | [180] |
Fe3O4@PMAO | RGD | ND | In vivo: rats bearing hepatic implants of colon adenocarcinoma | Therapeutic approach for poorly vascularized liver tumors | [181] |
Fe3O4 | EGFR— targeted peptide (YHWYGYTPQNVI) | ND | In vitro: lung cancer (NSCLC) In vivo: mouse orthotopic lung tumor model | Effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia | [182] |
TMNPs, i.e., Fe3O4@Mn0.5Zn0.5Fe2O4@CoFe2O4 | LN1 CPP | ND | In vitro: prostate cancer | Reduction in cancer cell aggressiveness | [183] |
SPIONs-PEG | membranotropic peptide gH625 | Cyanine 5.5 | In vitro: breast cancer cells | Prototype of nanoplatform for cancer theranostics involving magnetic resonance imaging, optical imaging (infrared), drug delivery, and hyperthermia | [184] |
6.2.3. Different Biomedical Applications of MNPs
Condition | Targeting Peptide | Nanocarrier | Advantages | Ref. |
---|---|---|---|---|
Conditions associated with Gram(+)/Gram(−) bacteria | Gly-Ala-Phe-Pro-His-Arg | Silica-coated iron oxide NPs |
| [185] |
GBM | NFL peptide | pSiNRs |
| [186] |
ALI | iNOS PNAs and CPPs | SCKs |
| [187] |
LC | TAT-functionalized IONPs | Fe3O4 + TAT |
| [188] |
UTIs | rGO/MPND with pyrene–PEG | rGO |
| [189] |
BC | Fe-Arg-MTX | IOMNPs |
| [190] |
7. Clinical and Cost-Effectiveness Analysis of Application THPs with MNPs
8. Future Perspectives
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Core Type | Av. Diameter | Interaction with THP | Application | Interaction with the Drug | Ref. |
---|---|---|---|---|---|
PEG polymer nanoparticles | 20–50 nm | covalent; conjugation by NHS ester | siRNA delivery | non-covalent interactions | [49] |
chemical complex | - | covalent; conjugation by maleimide | siRNA delivery | non-covalent interactions | [50] |
PEG polymer nanoparticles | nd | covalent; conjugation by maleimide | adenovirus vector carrier | covalent (by maleimide or NHS ester) | [86,87,88,89,90,91] |
PEG polymer nanoparticles | 141–160 nm | covalent; Michael reaction | paclitaxel delivery | non-covalent interactions | [92] |
PEG-PEI polymer nanoparticles | 100 nm | covalent; conjugation by NHS ester | siRNA delivery | non-covalent interactions | [93] |
PEG micelles | 32 nm | covalent; reaction with acetal | siRNA delivery | covalent (by maleimide or NHS ester) | [94] |
chitosan–PEG micelles | 260 nm | covalent; esterification reaction | siRNA delivery | non-covalent interactions | [95] |
PEG-PLA nanoparticles | 120 nm | covalent; conjugation by maleimide | siRNA delivery | non-covalent interactions | [96] |
mesoporous silica nanoparticles | 51.2 nm | non-covalent interactions | doxorubicin and siRNA | non-covalent interactions | [97] |
cationic liposome and PAA hybrid nanoparticles | 93 nm | non-covalent interactions | siRNA delivery | non-covalent interactions | [98] |
cyclodextrin | nd | non-covalent interactions | siRNA delivery | non-covalent interactions | [99] |
pHPMA polyplexes | 90–100 nm | covalent; amide bond formation | DNA delivery | non-covalent interactions | [100] |
biomimetic magnetic nanoparticles@PLGA copolymer | 220 nm | covalent; esterification reaction | drug delivery | nd | [101] |
Core | Ligand/Vector | Agent | Effect | Ref. |
---|---|---|---|---|
Atelocollagen | Aptamer APT A10-3.2 | miR15a, miR-16-1 | reduction in damage to the bone tissue improvement in the therapeutic effect | [50] |
PEG | Ac-YGGRGDTP(beta)A)(2)K-PEG-(beta)AC | Ads | modified adenovirus exhibited high gene expression even in a CAR-negative cell | [86] |
PEG | RGD-Ads | dnIkappaB | gene therapy/tool in rheumatoid arthritis and in IBD therapy | [87] |
Pluronic P85/PEI/TPGS | iRGD | PTX and survivin shRNA | powerful approach for the reversal and therapy of lung cancer resistance | [92] |
PEG-b-PLL(2IT) | cRGD | SiRNAs | antiangiogenic therapy—suppression of angiogenesis and tumor growth rate | [94] |
Chitosan–PEG | CP15 peptide | PLK1-siRNA | lack of systemic toxicity/potential approach for cancer therapy | [95] |
Multi-layered nanocomplexes MNS/PAH-Cit/GTC | TAT peptide | DOX/VEGF-siRNA | strong anticancer effect | [97] |
PLGA/lipid | iRGD | ICG/TPZ | delivery platform for PDT and hypoxia-activated chemotherapy | [63] |
Peptide | Target | Agent | Ref. |
---|---|---|---|
Interleukin 13 peptide (IL-13p) | IL13Rα2 | docetaxel | [119] |
Tuftsin (TKPR) | Neuropilin-1 (NRP-1) | anthracyclines salicylanilides | [120,121,122] |
tLyP-1 | Neuropilin-1 (NRP-1) | 5–carboxyfluorescein (FAM), 18F–fluoride | [123,124,125] |
Azurin (Paz) | TKR | - | [126] |
TGN | BBB AS1411 aptamer | docetaxel | [127,128] |
Angiopep-2 | LRP1 | doxorubicin | [128] |
Trans-activating transcriptional activator (TAT peptide) | Nucleus | siRNA expression plasmid, docetaxel, paclitaxel | [129,130] |
Chlorotoxin (CTX) | Tumor cell surface receptor; MMP-2 | platinum | [131,132] |
BTP-7 | dg-Bcan protein | camptothecin | [133] |
I. 68Ga-THP-PSMA PET/CT Imaging in High-Risk Primary Prostate Cancer or Biochemical Recurrence of Prostate Cancer (PRONOUNCED) [193] (49 Participants) Condition or Disease: Prostate Cancer | ||||
Selected Study Details | Arms and Interventions | Brief Description | Clinical Analysis | Cost-Effectiveness Analysis |
Official Study Title: A Phase II, Open-label Study to Assess Safety and Clinical Utility of 68Ga-THP-PSMA PET/CT in Patients With High Risk Primary Prostate Cancer or Biochemical Recurrence After Radical Treatment (PRONOUNCED Study) Study Phase: 2 Study Objectives: Diagnostic Study Design: Interventional (Single Group Assignment), Open Label Study Status: Completed (June, 2019) | Arm: 1. Experimental: Single i.v. administration of Gallium-68 THP-PSMA Intervention/treatment: 1. Drug: Gallium-68 THP-PSMA (other name: THG-001) | Brief Summary:
| Primary Outcome Measures: 1. Change in Patient Management—Measured as % of patients who had a change in management plan as a result of 68Ga-THP-PSMA PET/CT documented after scan, compared with their pre-scan management plan Results:
1. Safety—Treatment of Emergent AEs Safety was assessed by
| Increase in
|
II. Pre-Operative Nodal Staging of Thyroid Cancer Using USPIO MRI: Preliminary Study (12 Participants) [194] Condition or Disease: Thyroid Cancer | ||||
Selected Study Details | Arms and Interventions | Brief Description | Clinical Analysis | Cost-Effectiveness Analysis |
Official Study Title: Pre-Operative Nodal Staging of Thyroid Cancer Using Ultra-Small Superparamagnetic Iron Oxide Magnetic Resonance Imaging (USPIO MRI): Preliminary Study Study Phase: N/A Study Objectives: Diagnostic Study Design: Interventional (Single Group Assignment, Open Label) Study Status: Completed (April, 2016) | Arm: 1. Experimental: Nanoparticle MRI Within 48–72 h after ferumoxytol infusion, a scan will be performed Intervention/treatment: 1. Drug: Ferumoxytol i.v. administration at dose of 6 mg/kg of body weight, up to a maximum dose of 510 mg, delivered at a rate of up to 1 mL/s (other name: iron oxide-ferumoxytol) 2. Device: Nanoparticle MRI within 48–72 h after i.v. ferumoxytol infusion, and a scan will be performed | Brief Summary:
| Primary Outcome Measures:
| Increase in
|
III. Clinical and Technical Feasibility of an Ultrasuperparamagnetic Nanoparticle Iron Oxide (USPIO)-Enhanced Magnetic Resonance Lymph Node Imaging [195] (10 Participants) Condition or Disease: Cancer of Lymph Nodes | ||||
Selected Study Details | Arms and Interventions | Brief Description | Clinical Analysis | Cost-Effectiveness Analysis |
Official Study Title: Clinical and Technical Feasibility of a Ultrasuperparamagnetic Nanoparticle Iron Oxide (USPIO)-Enhanced Magnetic Resonance Lymph Node Imaging Study Phase: N/A Study Objectives: Diagnostic Study Design: Interventional (Single Group Assignment), Open Label Study Status: Completed (July 2019) | Arm: 1. Experimental: Feraheme MRI within 48–72 h after i.v. administration of Feraheme® Intervention/treatment: 1. Drug: Feraheme i.v. administration at dose of 6 mg of iron/kg (maximum: 510 mg/dose) at a rate of 1 mL/s (30 mg/s) or slower after initial MRI (other name: ferumoxytole) 2. Procedure: MRI MRI scan performed:
| Brief Summary:
| Primary Outcome Measures: 1. No. of patients with SI change in a lymph node—comparison between the pre- and post-contrast Results:
| Increase in
|
IV. Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI) [196] (35 Participants) Condition or Disease: Pancreatic Cancer | ||||
Selected Study Details | Arms and Interventions | Brief Description | Clinical Analysis | Cost-Effectiveness Analysis |
Official Study Title: Improved Pre-Operative Staging of Pancreatic Cancer Using Superparamagnetic Iron Oxide Magnetic Resonance Imaging (SPIO MRI) Study Phase: 4 Study Objectives: Diagnostic Study Design: Interventional (Single Group Assignment), Open Label Study Status: Completed (February 2013) | Arm: 1. Experimental: SPIO MRI Intervention/treatment: 1. Drug: SPIO MRI Two MRIs will be performed over a 2-day period. The second scan will be performed 48 h after i.v. administration of ferumoxytol (other names: SPIO MRI, USPIO, feruoxytol) | Brief Summary:
| Primary Outcome Measures:
| Increase in
|
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Milewska, S.; Sadowska, A.; Stefaniuk, N.; Misztalewska-Turkowicz, I.; Wilczewska, A.Z.; Car, H.; Niemirowicz-Laskowska, K. Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective. Int. J. Mol. Sci. 2024, 25, 6219. https://doi.org/10.3390/ijms25116219
Milewska S, Sadowska A, Stefaniuk N, Misztalewska-Turkowicz I, Wilczewska AZ, Car H, Niemirowicz-Laskowska K. Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective. International Journal of Molecular Sciences. 2024; 25(11):6219. https://doi.org/10.3390/ijms25116219
Chicago/Turabian StyleMilewska, Sylwia, Anna Sadowska, Natalia Stefaniuk, Iwona Misztalewska-Turkowicz, Agnieszka Z. Wilczewska, Halina Car, and Katarzyna Niemirowicz-Laskowska. 2024. "Tumor-Homing Peptides as Crucial Component of Magnetic-Based Delivery Systems: Recent Developments and Pharmacoeconomical Perspective" International Journal of Molecular Sciences 25, no. 11: 6219. https://doi.org/10.3390/ijms25116219