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Novel Water-Borne Polyurethane Nanomicelles for Cancer Chemotherapy: Higher Efficiency of Folate Receptors Than TRAIL Receptors in a Cancerous Balb/C Mouse Model

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ABSTRACT

Purpose

Since the introduction of nanocarriers, the delivery of chemotherapeutic agents for treatment of patients with cancer has been possible with better effectiveness. The latest findings are also support that further enhancement in therapeutic effectiveness of these nanocarriers can be attained, if surface decoration with proper targeting agents is considered.

Methods

This study aimed at treating a variety of 4T1 murine breast cancer cell line, mainly demonstrating high folate and TRAIL receptor expression of cancerous cells. The therapeutic efficacy of paclitaxel loaded Cremophore EL (Taxol®), paclitaxel loaded waterborne polyurethane nanomicelles (PTX-PU) and paclitaxel loaded waterborne polyurethane nanomicelles conjugated with folate (PTX-PU-FA) and TRAIL (PTX-PU-TRAIL) on treating 4T1 cell was also compared.

Results

The findings that worth noting are: PTX-PU outperformed Taxol® in a Balb/C mouse model, furthermore, tumor growth was adequately curbed by folate and TRAIL-decorated nanomicelles rather than the unconjugated formulation. Tumors of mice treated with PTX-PU-FA and PTX-PU-TRAIL shrank substantially compared to those treated with Taxol®, PTX-PU and PTX-PU-TRAIL (average 573 mm3 versus 2640, 846, 717 mm3 respectively), 45 days subsequent to tumor inoculation. The microscopic study of hematoxylin-eosin stained tumors tissue and apoptotic cell fraction substantiated that the most successful therapeutic effects have been observed for the mice treated with PTX-PU-FA (about 90% in PTX-PU-FA versus 75%, 60%, 15% in PTX-PU-TRAIL, PTX-PU, and Taxol® group respectively).

Conclusions

Using folate-targeted nanocarriers to treat cancers characterized by a high level of folate ligand expression is well substantiated by the findings of this study.

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Abbreviations

CMC:

Critical micelle concentration

DLS:

Dynamic light scattering

DMPA:

Dimethylolpropionic acid

DMSO:

Ddimethyl sulfoxide

FR:

Folate receptor

H&E:

Hematoxylin-eosin

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NMP:

N-methyl-2-pyrrolidone

PTMEG:

Poly(tetramethylene ether) glycol

PTX:

Paclitaxel

PUs:

Polyurethanes

TDI:

Toluene diisocyanate

TEA:

Triethanolamine

TRAIL:

TNF-related apoptosis-including ligand

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ACKNOWLEDGMENTS AND DISCLOSURES

The financial support of the Tabriz University of Medical Sciences is gratefully acknowledged. The authors declare that there are no conflicts of interests.

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    Authors and Affiliations

    1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

      Elham Ajorlou

    2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran

      Elham Ajorlou

    3. Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran

      Elham Ajorlou

    4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

      Ahmad Yari Khosroushahi

    5. Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran, P.O.Box 51664-14766

      Ahmad Yari Khosroushahi

    6. Polyurethanes Department Faculty of Polymer Science, Iran Polymer & Petrochemical Institute (IPPI), P.O.Box: 14965/115, Tehran, Iran

      Hamid Yeganeh

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    1. Elham Ajorlou
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    Correspondence to Ahmad Yari Khosroushahi or Hamid Yeganeh.

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    Elham Ajorlou and Ahmad Yari Khosroushahi contributed equally to this work.

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    Ajorlou, E., Khosroushahi, A.Y. & Yeganeh, H. Novel Water-Borne Polyurethane Nanomicelles for Cancer Chemotherapy: Higher Efficiency of Folate Receptors Than TRAIL Receptors in a Cancerous Balb/C Mouse Model. Pharm Res 33, 1426–1439 (2016). https://doi.org/10.1007/s11095-016-1884-6

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