Multi-modal strategies for overcoming tumor drug resistance: Hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology

Milane, Lara; Ganesh, Shanthi; Shah, Shruti; Duan, Zhenfeng; Amiji, Mansoor M.

doi:10.1016/j.jconrel.2011.03.032

Cited by 116 publications

(81 citation statements)

References 113 publications

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“…Under hypoxic conditions, tumor cells switch from oxygen-dependent glucose metabolism to anaerobic glycolysis (6). This cellular adaptation to hypoxia, known as the Warburg effect, is supported by an observed increase in glucose transport and consumption (7). High rates of glucose uptake and glycolysis supply the energy required for proliferation of malignant cells and tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lǚ

Yang

et al. 2016

Oncology Letters

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Abstract.Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18 F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUV max ) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUV max value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Lǚ

Yang

et al. 2016

Oncology Letters

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“…Subsequently, chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare TCAD@Ce6 nanoparticles (TCAD@Ce6 NPs), with TPGS as the hydrophilic shell, and chlorin e6 and DOX as the hydrophobic core. Thanks to the characteristic lower pH value present in tumor tissues and also in some intracellular vesicles as endosomes and lysosomes, 5,33 the acid-sensitive amide linker present in our TCAD@Ce6 nanoparticles acts as "OFF/ON" switch. Under ideal circumstances, our theranostic nanoparticles would not leak DOX and would self-quench the fluorescence of Ce6 by π-π interactions in blood circulation.…”

Section: 3mentioning

confidence: 99%

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

et al. 2016

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The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions ( pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo-photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo-photodynamic system for theranostics of lung cancer, etc. in the near future.

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“…More advanced 3D models can also add more intricate modifications such as the biochemical activity of the tumor, thereby creating a different tumor microenvironment that induces a higher chemoresistance and, more in general, different cell response. 146 Such effects are of prime interest when using bubbles as the local carriers (Fig. 2).…”

Section: Agent Behavior and Tissue Typementioning

confidence: 99%

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

et al. 2016

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Besides their use as contrast agents for ultrasound imaging, microbubbles are increasingly studied for a wide range of therapeutic applications. In particular, their ability to enhance the uptake of drugs through the permeabilization of tissues and cell membranes shows great promise. In order to fully understand the numerous paths by which bubbles can interact with cells and the even larger number of possible biological responses from the cells, thorough and extensive work is necessary. In this review, we consider the range of experimental techniques implemented in in vitro studies with the aim of elucidating these microbubble-cell interactions. First of all, the variety of cell types and cell models available are discussed, emphasizing the need for more and more complex models replicating in vivo conditions together with experimental challenges associated with this increased complexity. Second, the different types of stabilized microbubbles and more recently developed droplets and particles are presented, followed by their acoustic or optical excitation methods. Finally, the techniques exploited to study the microbubble-cell interactions are reviewed. These techniques operate over a wide range of timescales, or even off-line, revealing particular aspects or subsequent effects of these interactions. Therefore, knowledge obtained from several techniques must be combined to elucidate the underlying processes. V C 2016 AIP Publishing LLC.

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Multi-modal strategies for overcoming tumor drug resistance: Hypoxia, the Warburg effect, stem cells, and multifunctional nanotechnology

Cited by 116 publications

References 113 publications

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

Expression and clinical significance of glucose transporter-1 in pancreatic cancer

pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo–photodynamic combination therapy

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

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