Targeted Delivery of Cisplatin to Tumor Xenografts Via the Nanoparticle Component of nano-diamino-tetrac

Sudha, Thangirala; Bharali, Dhruba J.; Yalçın, Murat; Darwish, Noureldien H. E.; Coşkun, Melis Debreli; Keating, Kelly A.; Lin, Hung Yun; Davis, Paul J.; Mousa, Shaker A.

doi:10.2217/nnm-2016-0315

Cited by 42 publications

(42 citation statements)

References 31 publications

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“…13 The goal of the delivery system is to achieve increased anticancer drug content within tumors and to reduce systemic toxicity. Evidence presented in this article and in a companion article on cisplatin delivery 23 validates this concept. We show here that the loading with paclitaxel or doxorubicin of the PLGA nanoparticle covalently linked to NDAT resulted in a 5-fold increase in the tumor content of paclitaxel and a 2.3-fold increase in tumor doxorubicin compared to conventional drug administration.…”

Section: Discussionsupporting

confidence: 57%

“…In the companion article in which the tumor delivery of cisplatin by NDAT was studied, we also found a 5-fold enhancement of tumor content of drug, compared to conventionally administered cisplatin. 23 The multifold increase in the tumor content of each of these widely used anticancer drugs supports the existence of the cancer-targeting property of NDAT. 31,32 NDAT (Nanotetrac), alone, is an anticancer agent, but the dose of NDAT (0.3 mg/kg daily) used in the current studies to deliver generic chemotherapeutic agents was suboptimal in terms of NDAT chemotherapeutic efficacy.…”

Section: Discussionmentioning

confidence: 95%

“…The substantial progress made elsewhere in the development of targeted PLGA-based anticancer drug delivery systems has been reviewed by van der Meel et al 14 and Iyer et al 15 Recently described cancer cell-targeting moieties 18 transferrin, 19 chemokine-targeting peptide, 20 modified epidermal growth factor (EGF), 21 and arginine-glycine-aspartic acid (RGD) peptide. 22 In a companion article, 23 we report the use of this delivery system to enhance cisplatin uptake by tumor xenografts and to reduce cisplatin-induced neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Sudha

Bharali

Yalçın

et al. 2017

IJN

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The tetraiodothyroacetic acid (tetrac) component of nano-diamino-tetrac (NDAT) is chemically bonded via a linker to a poly(lactic- co -glycolic acid) nanoparticle that can encapsulate anticancer drugs. Tetrac targets the plasma membrane of cancer cells at a receptor on the extracellular domain of integrin αvβ3. In this study, we evaluate the efficiency of NDAT delivery of paclitaxel and doxorubicin to, respectively, pancreatic and breast cancer orthotopic nude mouse xenografts. Intra-tumoral drug concentrations were 5-fold (paclitaxel; P <0.001) and 2.3-fold (doxorubicin; P <0.01) higher than with conventional systemic drug administration. Tumor volume reductions reflected enhanced xenograft drug uptake. Cell viability was estimated by bioluminescent signaling in pancreatic tumors and confirmed an increased paclitaxel effect with drug delivery by NDAT. NDAT delivery of chemotherapy increases drug delivery to cancers and increases drug efficacy.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Sudha

Bharali

Yalçın

et al. 2017

IJN

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“…However, data demonstrated that treatment with anti-angiogenic drugs results in a more efficient normalized vasculature that might allow for improved tumor delivery of drugs [63,64,65,66,67,68,69,70]. Additionally, other anti-angiogenesis strategies such as anti-αvβ3 integrin have been exploited for enhanced active targeted delivery into tumors [71,72]. …”

Section: Side Effects In Anti-angiogenic Therapymentioning

confidence: 99%

The Role of Angiogenesis in Cancer Treatment

2017

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A number of anti-angiogenesis drugs have been FDA-approved and are being used in cancer treatment, and a number of other agents are in different stages of clinical development or in preclinical evaluation. However, pharmacologic anti-angiogenesis strategies that arrest tumor progression might not be enough to eradicate tumors. Decreased anti-angiogenesis activity in single mechanism-based anti-angiogenic strategies is due to the redundancy, multiplicity, and development of compensatory mechanism by which blood vessels are remodeled. Improving anti-angiogenesis drug efficacy will require identification of broad-spectrum anti-angiogenesis targets. These strategies may have novel features, such as increased porosity, and are the result of complex interactions among endothelial cells, extracellular matrix proteins, growth factors, pericyte, and smooth muscle cells. Thus, combinations of anti-angiogenic drugs and other anticancer strategies such as chemotherapy appear essential for optimal outcome in cancer patients. This review will focus on the role of anti-angiogenesis strategies in cancer treatment.

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“…Tetraiodothyroacetic acid (tetrac) is a deaminated analog of T 4 that competes with thyroid hormone for a target or receptor on cell surface integrin α v β 3 and blocks the activity of thyroid hormone at this site . In addition to blocking the binding of thyroid hormone to integrin α v β 3 , tetrac and its nanoparticulate derivative nano‐diamino‐tetrac inhibit cancer cell proliferation and angiogenesis by disordering the expression of a number of genes relevant to apoptosis and blood vessel formation.…”

Section: The Interactions Between Steroid Hormones and Resveratrolmentioning

confidence: 99%

Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

Lin

Hsieh

Cheng

et al. 2017

Annals of the New York Academy of Sciences

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Nonpeptide hormones, such as thyroid hormone, dihydrotestosterone, and estrogen, have been shown to stimulate cancer proliferation via different mechanisms. Aside from their cytosolic or membrane-bound receptors, there are receptors on integrin α β for nonpeptide hormones. Interaction between hormones and integrin α β can induce signal transduction and eventually stimulate cancer cell proliferation. Resveratrol induces inducible COX-2-dependent antiproliferation via integrin α β . Resveratrol and hormone-induced signals are both transduced by activated extracellular-regulated kinases 1 and 2 (ERK1/2); however, hormones promote cell proliferation, while resveratrol induces antiproliferation in cancer cells. Hormones inhibit resveratrol-stimulated phosphorylation of p53 on Ser15, resveratrol-induced nuclear COX-2 accumulation, and formation of p53-COX-2 nuclear complexes. Subsequently, hormones impair resveratrol-induced COX-2-/p53-dependent gene expression. The inhibitory effects of hormones on resveratrol action can be blocked by different antagonists of specific nonpeptide hormone receptors but not integrin α β blockers. Results suggest that nonpeptide hormones inhibit resveratrol-induced antiproliferation in cancer cells downstream of the interaction between ligand and receptor and ERK1/2 activation to interfere with nuclear COX-2 accumulation. Thus, the surface receptor sites for resveratrol and nonpeptide hormones are distinct and can induce discrete ERK1/2-dependent downstream antiproliferation biological activities. It also indicates the complex pathways by which antiproliferation is induced by resveratrol in various physiological hormonal environments. .

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Targeted Delivery of Cisplatin to Tumor Xenografts Via the Nanoparticle Component of nano-diamino-tetrac

Abstract: NDAT markedly enhances cisplatin delivery to urinary bladder cancer xenografts and increases drug efficacy.

Cited by 42 publications

References 31 publications

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

Targeted delivery of paclitaxel and doxorubicin to cancer xenografts via the nanoparticle of nano-diamino-tetrac

The Role of Angiogenesis in Cancer Treatment

Mechanisms of action of nonpeptide hormones on resveratrol‐induced antiproliferation of cancer cells

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