Utilizing the folate receptor for active targeting of cancer nanotherapeutics

Zwicke, Grant; Mansoori, G. Ali; Jeffery, Constance J.

doi:10.3402/nano.v3i0.18496

Cited by 428 publications

(300 citation statements)

References 54 publications

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“…The inhibition of specific steps of the folate metabolism leads to a depletion of intracellular folates, which finally provoke cytotoxic effects, particularly by impairing DNA synthesis, methylation, and repair. [22][23][24] However, MTX shows heterogeneous toxicity and resistances among different tumor entities, which result from several mechanisms including alterations in various transport mechanisms responsible for the uptake and/or efflux of MTX from the cell. 25 The two main transport mechanisms responsible for the uptake of MTX by cells are the folate receptor (FR) and the reduced folate carrier (RFC).…”

Section: Introductionmentioning

confidence: 99%

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Stapf¹,

Pömpner²,

Teichgräber³

et al. 2016

IJN

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Today, the therapeutic efficacy of cancer is restricted by the heterogeneity of the response of tumor cells to chemotherapeutic drugs. Since those therapies are also associated with severe side effects in nontarget organs, the application of drugs in combination with nanocarriers for targeted therapy has been suggested. Here, we sought to assess whether the coupling of methotrexate (MTX) to magnetic nanoparticles (MNP) could serve as a valuable tool to circumvent the heterogeneity of tumor cell response to MTX by the combined treatment with hyperthermia. To this end, we investigated five breast cancer cell lines of different origin and with different mutational statuses, as well as a bladder cancer cell line in terms of their response to exposure to MTX as a free drug or after its coupling to MNP as well as in presence/absence of hyperthermia. We also assessed whether the effects could be connected to the cell line-specific expression of proteins related to the uptake and efflux of MTX and MNP. Our results revealed a very heterogeneous and cell line-dependent response to an exposure with MTX-coupled MNP (MTX–MNP), which was almost comparable to the efficacy of free MTX in the same cell line. Moreover, a cell line-specific and preferential uptake of MTX–MNP compared with MNP alone was found (probably by receptor-mediated endocytosis), agreeing with the observed cytotoxic effects. Opposed to this, the expression pattern of several cell membrane transport proteins noted for MTX uptake and efflux was only by tendency in agreement with the cellular toxicity of MTX–MNP in different cell lines. Higher cytotoxic effects were achieved by exposing cells to a combination of MTX–MNP and hyperthermal treatment, compared with MTX or thermo-therapy alone. However, the heterogeneity in the response of the tumor cell lines to MTX could not be completely abolished – even after its combination with MNP and/or hyperthermia – and the application of higher thermal dosages might be necessary.

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Section: Introductionmentioning

confidence: 99%

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Stapf¹,

Pömpner²,

Teichgräber³

et al. 2016

IJN

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“…The folate receptor is overexpressed in various types of cancer such as breast, ovarian, lung, colon, kidney, and brain cancers [29]. It has two isoforms: the alpha isoform, which is overexpressed in most cancers, and the beta isoform, which is expressed on the surface of activated macrophages [2].…”

Section: Active Targeting Of Tumor Cellsmentioning

confidence: 99%

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

Porfire¹,

Achim²,

Tefas³

et al. 2017

Liposomes

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The liposomes present great potential for applications in targeted delivery of chemotherapeutics in the treatment of cancer. The use of liposomal drug carriers as vehicles for targeting of chemotherapeutic agents to tumor tissues is based on their advantages over other dosage forms, represented by their low systemic toxicity, their bioavailability, and their possibility to enhance the solubility of different chemotherapeutic agents, due to the ability to encapsulate both hydrophilic and lipophilic drugs. They enhance the therapeutic index of anticancer drugs by increasing the drug concentration in tumor cells through tumor targeting. The available approaches used for tumor targeting using liposomes are passive targeting, active targeting, and triggered drug release. The most advanced targeting strategies proposed for cancer treatment are the development of multifunctional liposomes, having combined targeting mechanism. In this chapter, the tumor-targeting mechanisms are described in detail as well as the possibilities to design the targeted liposomal nanocarrier in order to reach the desired target in the body and minimizing the off-target effects. Moreover, the current status of preclinical and clinical evaluation is highlighted.

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“…123 The folate receptor has also been recognized as a tumor marker as it is overly overexpressed on the surface of different cancers making it a good target for folate nanoconjugates. 126 For example, various folic acid functionalized polyethylenimine (PEI) polymers were evaluated to deliver PD-L1 siRNA to SKOV-3-Luc epithelial ovarian cancer cells. Folic acid modified PEI polymers increased siRNA uptake into SKOV-3-luc cells and decreased non-specific uptake into monocytes resulting in enhanced T cell killing.…”

Section: Combination Therapymentioning

confidence: 99%

Potential applications of nanoparticles in cancer immunotherapy

Jia

Omri

Krishnan

et al. 2016

Human Vaccines & Immunotherapeutics

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In recent years considerable progress has been made in the field of cancer immunotherapy whereby treatments that modulate the body's own immune system are used to combat cancer. This has the potential to not only elicit strong anti-cancer immune responses which can break pre-existing tolerance and help promote tumor regression, but could also induce immunological memory which may help prevent tumor recurrence. In order to ensure effective delivery of immunotherapeutic agents, such as vaccines, checkpoint inhibitors, chemotherapeutic agents and nucleic acids, a safe and effective delivery system is often required. One such approach is the use of multifunctional nanoparticles (NPs), such as liposomes, polymers, micelles, dendrimers, inorganic NPs, and hybrid NPs, which have the potential to combine the delivery of a diverse range of therapeutic immunomodulators thereby increasing the efficacy of tumor cell killing. This review focuses on recent progress in NP-mediated immunotherapy for the treatment of cancer.

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Utilizing the folate receptor for active targeting of cancer nanotherapeutics

Cited by 428 publications

References 54 publications

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Heterogeneous response of different tumor cell lines to methotrexate-coupled nanoparticles in presence of hyperthermia

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

Potential applications of nanoparticles in cancer immunotherapy

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