Examining expression of folate receptor in squamous cell carcinoma of the head and neck as a target for a novel nanotherapeutic drug

Saba, Nabil F.; Wang, Xu; Müller, Susan; Tighiouart, Mourad; Cho, Kwangjae; Nie, Shuming; Chen, Zhuo; Shin, Dong M.

doi:10.1002/hed.21003

Cited by 50 publications

(31 citation statements)

References 29 publications

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“…We have checked the incidence of folate receptor expression in human head and neck primary and metastatic tumor tissues and compared them with normal tissues such as the bone marrow. Folate receptor expression was found in 53% of these tumor samples whereas normal bone marrow cells did not show any folate receptor expression (47). Recently, we generated a new folate receptor -targeted nanoparticle formulation of paclitaxel using heparin as a carrier [heparin-folate-Taxol (paclitaxel), HFT] and tested it using nude mouse animal models.…”

Section: Therapeutic Application Of Ligand-targeted Nanoparticlesmentioning

confidence: 99%

Therapeutic Nanoparticles for Drug Delivery in Cancer

Cho

Wang

Nie

et al. 2008

Clinical Cancer Research

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Cancer nanotherapeutics are rapidly progressing and are being implemented to solve several limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, poor oral bioavailability, and low therapeutic indices. To improve the biodistribution of cancer drugs, nanoparticles have been designed for optimal size and surface characteristics to increase their circulation time in the bloodstream. They are also able to carry their loaded active drugs to cancer cells by selectively using the unique pathophysiology of tumors, such as their enhanced permeability and retention effect and the tumor microenvironment. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumor targets amplify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle that impedes the efficacy of both molecularly targeted and conventional chemotherapeutic agents, might also be overcome, or at least reduced, using nanoparticles. Nanoparticles have the ability to accumulate in cells without being recognized by P-glycoprotein, one of the main mediators of multidrug resistance, resulting in the increased intracellular concentration of drugs. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.

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Section: Therapeutic Application Of Ligand-targeted Nanoparticlesmentioning

confidence: 99%

Therapeutic Nanoparticles for Drug Delivery in Cancer

Cho

Wang

Nie

et al. 2008

Clinical Cancer Research

Self Cite

2,645

1,679

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“…11,12 Compared with nontargeted carriers, these new vectors can improve the gene transfection efficiency of FR-positive HEK 293T cells, C6 cells, and KB cells in vitro, 11,12 and have had stronger antitumor effects in experiments in vivo. 13 Chemotherapeutic drugs (eg, paclitaxel, doxorubicin) conjugated with FA have been shown not only to be selectively transported into KB cells, 14,15 Bel 7402 cells, 16 and nude mice xenograft tumors, but also to achieve better antitumor results. Saba et al detected the FR in 45% of primary squamous cell carcinomas of the head and neck and 40% of corresponding lymph node metastases.…”

Section: Introductionmentioning

confidence: 99%

“…Saba et al detected the FR in 45% of primary squamous cell carcinomas of the head and neck and 40% of corresponding lymph node metastases. 13 Ward et al made acetylated generation 5 dendrimers conjugated with FA and methotrexate as the therapeutic moiety in compound reagents and administered them to nude mice with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer xenografts. 17 They found this targeted therapy could be delivered in molar doses three times that of the free drug and with lower systemic toxicity.…”

Section: Introductionmentioning

confidence: 99%

Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

Xie¹,

Zhang²,

Xu³

et al. 2013

IJN

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Abstract:Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.

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“…A previous study indicated that folate receptors could be expressed significantly in the squamous cell carcinoma of the head and neck, both in primary tumors and in the corresponding lymph node metastases. 47 The high expression of folate receptors appeared to be correlated with the clinical outcomes. Folate receptors in metastatic lymph nodes suggested a strong potential for targeted chemotherapy in both primary tumor and metastasis.…”

Section: In Vitro Mri Scansmentioning

confidence: 96%

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

Li¹,

Li²,

Yi³

et al. 2013

IJN

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Purpose:To research the acid-triggered core cross-linked folate-poly(ethylene glycol)-b-poly [N-(N′,N′-diisopropylaminoethyl) glutamine] (folated-PEG-P[GA-DIP]) amphiphilic block copolymer for targeted drug delivery and magnetic resonance imaging (MRI) in liver cancer cells. Methods:As an appropriate receptor of protons, the N,N-diisopropyl tertiary amine group (DIP) was chosen to conjugate with the side carboxyl groups of poly(ethylene glycol)-b-poly (L-glutamic acid) to obtain PEG-P(GA-DIP) amphiphilic block copolymers. By ultrasonic emulsification, PEG-P(GA-DIP) could be self-assembled to form nanosized micelles loading doxorubicin (DOX) and superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution. When PEG-P(GA-DIP) nanomicelles were combined with folic acid, the targeted effect of folated-PEG-P(GA-DIP) nanomicelles was evident in the fluorescence and MRI results. Results: To further increase the loading efficiency and the cell-uptake of encapsulated drugs (DOX and SPIONs), DIP (pK a ≈6.3) groups were linked with ∼50% of the side carboxyl groups of poly(L-glutamic acid) (PGA), to generate the core cross-linking under neutral or weakly acidic conditions. Under the acidic condition (eg, endosome/lysosome), the carboxyl groups were neutralized to facilitate disassembly of the P(GA-DIP) blocks' cross-linking, for duly accelerating the encapsulated drug release. Combined with the tumor-targeting effect of folic acid, specific drug delivery to the liver cancer cells and MRI diagnosis of these cells were greatly enhanced. Conclusion: Acid-triggered and folate-decorated nanomicelles encapsulating SPIONs and DOX, facilitate the targeted MRI diagnosis and therapeutic effects in tumors.

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Examining expression of folate receptor in squamous cell carcinoma of the head and neck as a target for a novel nanotherapeutic drug

Cited by 50 publications

References 29 publications

Therapeutic Nanoparticles for Drug Delivery in Cancer

Therapeutic Nanoparticles for Drug Delivery in Cancer

Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

Acid-triggered core cross-linked nanomicelles for targeted drug delivery and magnetic resonance imaging in liver cancer cells

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