Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

Wang, Qi; Alshaker, Heba; Böhler, Torsten; Srivats, Shyam; Chao, Yimin; Cooper, Christopher S.; Pchejetski, Dmitri

doi:10.1038/s41598-017-06142-x

Cited by 50 publications

(36 citation statements)

References 37 publications

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“…To improve the efficacy and tolerability of fingolimod, second-generation derivatives and complex pharmaceutical formulations were engineered and tested in various preclinical tumor models. These include the analog OSU-2S, which shows reduced S1PR modulation and increased inhibition of tumor cell proliferation (Omar et al, 2011), lipid-encapsulated ingolimod for oral delivery (Estella-Hermoso de Mendoza et al, 2015), nanoparticles combining fingolimod with docetaxel Wang et al, 2017), and fingolimod-loaded nanocarriers targeting CD19, CD20 or CD37 (Mao et al, 2014). However, again, these new developments were tested at clinically unrealistic mg/kg doses and therefore conclusions for anti-tumor activity in patients cannot be drawn.…”

Section: S1pr-independent Effects (Off-target)mentioning

confidence: 99%

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Huwiler

Zangemeister‐Wittke

2018

Pharmacology & Therapeutics

176

134

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The immunomodulatory drug fingolimod (FTY720, Gilenya) was approved for oral treatment of relapsing-remitting multiple sclerosis, due to its impressive efficacy and good tolerability. Pharmacologically, it acts as an unselective agonist of sphingosine 1-phosphate receptors (S1PR) and as a selective functional antagonist of the S1P subtype by induction of receptor downregulation. Since S1P is crucial for the regulation of lymphocyte trafficking, its downregulation causes redistribution of the immune cells to secondary lymphoid tissues, resulting in the depletion from the circulation and hence immunosuppression. Numerous preclinical studies have since been performed with the aim to increase the spectrum of potential indications for fingolimod with emphasis on other autoimmune disorders and diseases associated with inflammation and uncontrolled cell proliferation, including cancer. As an alternative to fingolimod, novel S1PR modulators with a more selective receptor activation profile and improved pharmacokinetic performance and tolerability have also been developed. Preclinical and clinical studies are ongoing to investigate their therapeutic potential. This review discusses the most relevant preclinical and clinical findings from S1PR-targeting and from less-well defined off-target effects reported in the literature, and reveals perspectives for using fingolimod and functionally-related derivatives and new formulations in the management of an increasing number of diseases.

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Section: S1pr-independent Effects (Off-target)mentioning

confidence: 99%

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Huwiler

Zangemeister‐Wittke

2018

Pharmacology & Therapeutics

176

134

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“…Many strategies, including passive and active targeting, have thus been utilized to enable the efficient delivery of drugs to cancer cells. [ 49 , 50 , 51 ]. These strategies are used for the development of targeted anti-cancer therapies.…”

Section: Targetingmentioning

confidence: 99%

“…Active targeting depends on the biological interactions between the outer cells, targeting ligands, and the specific target cells. Currently, researchers are mainly focusing on active targeting strategies involving PLHNPs for effective treatment for cancer [ 51 , 56 ].…”

Section: Active Targeting With Surface Engineered Plhnpsmentioning

confidence: 99%

Utilization of Polymer-Lipid Hybrid Nanoparticles for Targeted Anti-Cancer Therapy

2020

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Cancer represents one of the most dangerous diseases, with 1.8 million deaths worldwide. Despite remarkable advances in conventional therapies, these treatments are not effective to completely eradicate cancer. Nanotechnology offers potential cancer treatment based on formulations of several nanoparticles (NPs). Liposomes and polymeric nanoparticle are the most investigated and effective drug delivery systems (DDS) for cancer treatment. Liposomes represent potential DDS due to their distinct properties, including high-drug entrapment efficacy, biocompatibility, low cost, and scalability. However, their use is restricted by susceptibility to lipid peroxidation, instability, burst release of drugs, and the limited surface modification. Similarly, polymeric nanoparticles show several chemical modifications with polymers, good stability, and controlled release, but their drawbacks for biological applications include limited drug loading, polymer toxicity, and difficulties in scaling up. Therefore, polymeric nanoparticles and liposomes are combined to form polymer-lipid hybrid nanoparticles (PLHNPs), with the positive attributes of both components such as high biocompatibility and stability, improved drug payload, controlled drug release, longer circulation time, and superior in vivo efficacy. In this review, we have focused on the prominent strategies used to develop tumor targeting PLHNPs and discuss their advantages and unique properties contributing to an ideal DDS.

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“…There is now evidence that nanoparticle-based therapies are advantageous due to characteristics such as targeted drug delivery and precise kinetics of release (123,151). Additionally, nanocarriers may confer other properties, including imaging capability and minimization of toxicity, when used for delivery of combined therapies.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target

2020

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It is now well-established that sphingosine kinase 1 (SK1) plays a significant role in breast cancer development, progression, and spread, whereas SK1 knockdown can reverse these processes. In breast cancer cells and tumors, SK1 was shown to interact with various pathways involved in cell survival and chemoresistance, such as nuclear factor-kappa B (NFκB), Notch, Ras/MAPK, PKC, and PI3K. SK1 is upregulated by estrogen signaling, which, in turn, confers cancer cells with resistance to tamoxifen. Sphingosine-1-phosphate (S1P) produced by SK1 has been linked to tumor invasion and metastasis. Both SK1 and S1P are closely linked to inflammation and adipokine signaling in breast cancer. In human tumors, high SK1 expression has been linked with poorer survival and prognosis. SK1 is upregulated in triple negative tumors and basal-like subtypes. It is often associated with high phosphorylation levels of ERK1/2, SFK, LYN, AKT, and NFκB. Higher tumor SK1 mRNA levels were correlated with poor response to chemotherapy. This review summarizes the up-to-date evidence and discusses the therapeutic potential for the SK1 inhibition in breast cancer, with emphasis on the mechanisms of chemoresistance and combination with other therapies such as gefitinib or docetaxel. We have outlined four key areas for future development, including tumor microenvironment, combination therapies, and nanomedicine. We conclude that SK1 may have a potential as a target for precision medicine, its high expression being a negative prognostic marker in ER-negative breast cancer, as well as a target for chemosensitization therapy.

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Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer

Cited by 50 publications

References 37 publications

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: Recent findings and new perspectives

Utilization of Polymer-Lipid Hybrid Nanoparticles for Targeted Anti-Cancer Therapy

Sphingosine Kinase 1 in Breast Cancer—A New Molecular Marker and a Therapy Target

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