scholarly journals Near-infrared dye loaded polymeric nanoparticles for cancer imaging and therapy and cellular response after laser-induced heating

2014 ◽  
Vol 5 ◽  
pp. 313-322 ◽  
Author(s):  
Tingjun Lei ◽  
Alicia Fernandez-Fernandez ◽  
Romila Manchanda ◽  
Yen-Chih Huang ◽  
Anthony J McGoron

Background: In the past decade, researchers have focused on developing new biomaterials for cancer therapy that combine imaging and therapeutic agents. In our study, we use a new biocompatible and biodegradable polymer, termed poly(glycerol malate co-dodecanedioate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of near-infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT). HT is currently used in clinical trials for cancer therapy in combination with radiotherapy and chemotherapy. One of the potential problems of HT is that it can up-regulate hypoxia-inducible factor-1 (HIF-1) expression and enhance vascular endothelial growth factor (VEGF) secretion. Results: We explored cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NPs) induced-heating, and compared it to slow, long-term and high thermal dose heating by a cell incubator. The expression levels of the reactive oxygen species (ROS), HIF-1 and VEGF following the two different modes of heating. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. The ROS level was highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. Our results show that elevated ROS expression inside the cells could result in the promotion of HIF-1 expression after incubator induced-HT. The VEGF secretion was also significantly enhanced compared to laser/NP HT, possibly due to the promotion of HIF-1. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging. Conclusion: IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 507 ◽  
Author(s):  
Liu ◽  
Gao ◽  
Zhou ◽  
Nie ◽  
Cheng ◽  
...  

Abstract: The development of versatile nanoscale drug delivery systems that integrate with multiple therapeutic agents or methods and improve the efficacy of cancer therapy is urgently required. To satisfy this demand, polydopamine (PDA)-modified polymeric nanoplatforms were constructed for the dual loading of chemotherapeutic drugs. The hydrophobic anticancer drug docetaxel (DTX) was loaded into the polymeric nanoparticles (NPs) which were fabricated from the star-shaped copolymer CA-PLGA. Then DTX-loaded NPs were coated with PDA, followed by conjugation of polyelethyl glycol (PEG)-modified targeting ligand aptamer AS1411(Apt) and adsorption of the hydrophilic anticancer drug doxorubicin (DOX). This “four-in-one” nanoplatform, referred to as DTX/NPs@PDA/DOX-PEG-Apt, demonstrated high near-infrared photothermal conversion efficiency and exhibited pH and thermo-responsive drug release behavior. Furthermore, it was able to specifically target MCF-7 human breast carcinoma cells and provide synergistic chemo-photothermal therapy to further improve the anticancer effect both in vitro and in vivo, providing a novel promising strategy for cancer therapy.


2010 ◽  
Vol 46 (18) ◽  
pp. 3167 ◽  
Author(s):  
Fong-Yu Cheng ◽  
Chia-Hao Su ◽  
Ping-Ching Wu ◽  
Chen-Sheng Yeh

1989 ◽  
Vol 257 (2) ◽  
pp. F177-F181 ◽  
Author(s):  
C. Khadouri ◽  
S. Marsy ◽  
C. Barlet-Bas ◽  
A. Doucet

Because previous studies indicated that in the collecting tubule, N-ethylmaleimide (NEM)-sensitive ATPase, the biochemical equivalent of the proton pump, is controlled by mineralocorticoids in the long term, the present study was designed to investigate whether such control also exists in the short term. Therefore we investigated the in vivo and in vitro effects of aldosterone on the enzyme activity in cortical and outer medullary collecting tubules (CCT and MCT, respectively) from adrenalectomized rats. Administration of aldosterone (10 micrograms/kg body wt) markedly stimulated NEM-sensitive ATPase activity in the CCT and MCT within 3 h. Similarly, incubating CCT or MCT for 3 h in the presence of 10(-8) M aldosterone enhanced NEM-sensitive ATPase activity up to values similar to those previously measured in the corresponding nephron segments of normal rats. In vitro stimulation of NEM-sensitive ATPase was dose dependent in regard to aldosterone (apparent affinity constant approximately 10(-9) M), appeared after a 30-min lag period, and reached its maximum after 2-2.5 h. Finally, actinomycin D and cycloheximide totally abolished the in vitro action of aldosterone, demonstrating the involvement of protein synthesis in this process.


Nanomaterials ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 1360 ◽  
Author(s):  
Asma Khalid ◽  
Romina Norello ◽  
Amanda N. Abraham ◽  
Jean-Philippe Tetienne ◽  
Timothy J. Karle ◽  
...  

Imaging of biological matter by using fluorescent nanoparticles (NPs) is becoming a widespread method for in vitro imaging. However, currently there is no fluorescent NP that satisfies all necessary criteria for short-term in vivo imaging: biocompatibility, biodegradability, photostability, suitable wavelengths of absorbance and fluorescence that differ from tissue auto-fluorescence, and near infrared (NIR) emission. In this paper, we report on the photoluminescent properties of magnesium oxide (MgO) NPs that meet all these criteria. The optical defects, attributed to vanadium and chromium ion substitutional defects, emitting in the NIR, are observed at room temperature in NPs of commercial and in-house ball-milled MgO nanoparticles, respectively. As such, the NPs have been successfully integrated into cultured cells and photostable bright in vitro emission from NPs was recorded and analyzed. We expect that numerous biotechnological and medical applications will emerge as this nanomaterial satisfies all criteria for short-term in vivo imaging.


2018 ◽  
Vol 30 (8) ◽  
pp. 1154 ◽  
Author(s):  
Anne-Laure Nivet ◽  
Isabelle Dufort ◽  
Isabelle Gilbert ◽  
Marc-André Sirard

In reproduction, FSH is one of the most important hormones, especially in females, because it controls the number of follicles and the rate of follicular growth. Although several studies have examined the follicular response at the transcriptome level, it is difficult to obtain a clear and complete picture of the genes responding to an increase in FSH in an in vivo context because follicles undergo rapid morphological and physical changes during their growth. To help define the transcriptome downstream response to FSH, an in vitro model was used in the present study to observe the short-term (4 h) cellular response. Gene expression analysis highlighted a set of novel transcripts that had not been reported previously as being part of the FSH response. Moreover, the results of the present study indicate that the epithelial to mesenchymal transition pathway is inhibited by short-term FSH stimuli, maintaining follicles in a growth phase and preventing differentiation. Modulating gene expression in vitro has physiological limitations, but it can help assess the potential downstream response and begin the mapping of the granulosa cell transcriptome in relation to FSH. This information is a key feature to help discriminate between the effects of FSH and LH, or to elucidate the overlapping of insulin-like growth factor 1 and FSH in the granulosa mitogenic response.


2015 ◽  
Vol 51 (49) ◽  
pp. 10054-10057 ◽  
Author(s):  
Qin Liu ◽  
Chunyang Sun ◽  
Qun He ◽  
Daobin Liu ◽  
Adnan Khalil ◽  
...  

Uniform MoO2 nanoparticles coated with ultrathin carbon layers, synthesized by a solvothermal method, were demonstrated as a promising NIR photothermal agent by in vitro and in vivo tests.


1996 ◽  
Vol 16 (1) ◽  
pp. 81-88 ◽  
Author(s):  
M Tena-Sempere ◽  
L Pinilla ◽  
E Aguilar

ABSTRACT In the present work in vitro GH pituitary responsiveness to GHRH in short-term (STO) and long-term orchidectomized (LTO) male rats was compared. In agreement with previous data obtained in vivo, pituitaries from STO rats showed reduced GH release after GHRH stimulation while LTO male pituitaries presented responses similar to those from control animals after maximal GHRH (10-6 m) stimulation. This suggests that compensatory mechanisms have taken place, probably at the pituitary level, in order to restore GH pituitary responsiveness to high doses of GHRH. However, LTO male rats showed a reduced sensitivity to GHRH relative to intact males, as indicated by a higher EC50 vs controls (40·82 ± 12·03 nm vs 0·35 ± 0·09 nm in intact males). We aimed to investigate further the events involved in the compensatory mechanisms that take place in LTO rats. For this purpose, we compared in vitro GH secretion by pituitaries from intact and LTO male rats after stimulation with specific activators of the signal transduction pathways related to GH release. Forskolin and dibutyryl cyclic-adenosine 3′,5′-monophosphate were more effective in eliciting GH secretion (expressed in terms of percent increment over basal GH release) in LTO males, whereas phorbol 12-myristate 13-acetate was completely ineffective in stimulating GH release in this group. Thus, our results clearly showed that long-term orchidectomy enhances the effectiveness of the cAMP pathway in inducing GH release while it completely blunts that of the protein kinase C pathway. In conclusion, orchidectomy decreased the effectiveness of GHRH in eliciting GH release in vitro. However, long-term orchidectomy activated compensatory mechanisms that restored complete GH pituitary responsiveness to maximal GHRH stimulation. These mechanisms seem not to operate in STO rats. An increased effectiveness of the cAMP pathway in eliciting GH release in LTO rats is probably involved in the aforementioned compensatory mechanisms.


Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3781-3790 ◽  
Author(s):  
Ole Johan Borge ◽  
Jörgen Adolfsson ◽  
Annica Mårtensson, Inga-Lill Mårtensson, and Sten E.W. Jacobsen

Abstract The two tyrosine kinase receptors, c-kit and flt3, and their respective ligands KL and FL, have been demonstrated to play key and nonredundant roles in regulating the earliest events in hematopoiesis. However, their precise roles and potential interactions in promoting early lymphoid commitment and development remain unclear. Here we show that most if not all murine Lin−/loSca1+c-kit+ bone marrow (BM) cells generating B220+CD19+proB-cells in response to FL and interleukin-7 (IL-7) also have a myeloid potential. In contrast to FL + IL-7, KL + IL-7 could not promote proB-cell formation from Lin−/loSca1+c-kit+ cells. However, KL potently enhanced FL + IL-7–stimulated proB-cell formation, in part through enhanced recruitment of FL + IL-7–unresponsive Lin−/loSca1+c-kit+progenitors, and in part by enhancing the growth of proB-cells. The enhanced recruitment (4-fold) in response to KL occurred exclusively from the Lin−/loSca1+c-kit+flt3−long-term repopulating stem cell population, whereas KL had no effect on FL + IL-7–stimulated recruitment of Lin−/loSca1+c-kit+flt3+short-term repopulating cells. The progeny of FL + IL-7–stimulated Lin−/loSca1+c-kit+ cells lacked in vitro and in vivo myeloid potential, but efficiently reconstituted both B and T lymphopoiesis. In agreement with this FL, but not KL, efficiently induced expression of B220 and IL-7 receptor- on Lin−/loSca1+c-kit+flt3+cells. Thus, whereas KL appears crucial for recruitment of FL + IL-7–unresponsive candidate (c-kit+flt3−) murine stem cells, FL is essential and sufficient for development toward lymphoid restricted progenitors from a population of (c-kit+flt3+) multipotent short-term reconstituting progenitors.


Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3781-3790 ◽  
Author(s):  
Ole Johan Borge ◽  
Jörgen Adolfsson ◽  
Annica Mårtensson, Inga-Lill Mårtensson, and Sten E.W. Jacobsen

The two tyrosine kinase receptors, c-kit and flt3, and their respective ligands KL and FL, have been demonstrated to play key and nonredundant roles in regulating the earliest events in hematopoiesis. However, their precise roles and potential interactions in promoting early lymphoid commitment and development remain unclear. Here we show that most if not all murine Lin−/loSca1+c-kit+ bone marrow (BM) cells generating B220+CD19+proB-cells in response to FL and interleukin-7 (IL-7) also have a myeloid potential. In contrast to FL + IL-7, KL + IL-7 could not promote proB-cell formation from Lin−/loSca1+c-kit+ cells. However, KL potently enhanced FL + IL-7–stimulated proB-cell formation, in part through enhanced recruitment of FL + IL-7–unresponsive Lin−/loSca1+c-kit+progenitors, and in part by enhancing the growth of proB-cells. The enhanced recruitment (4-fold) in response to KL occurred exclusively from the Lin−/loSca1+c-kit+flt3−long-term repopulating stem cell population, whereas KL had no effect on FL + IL-7–stimulated recruitment of Lin−/loSca1+c-kit+flt3+short-term repopulating cells. The progeny of FL + IL-7–stimulated Lin−/loSca1+c-kit+ cells lacked in vitro and in vivo myeloid potential, but efficiently reconstituted both B and T lymphopoiesis. In agreement with this FL, but not KL, efficiently induced expression of B220 and IL-7 receptor- on Lin−/loSca1+c-kit+flt3+cells. Thus, whereas KL appears crucial for recruitment of FL + IL-7–unresponsive candidate (c-kit+flt3−) murine stem cells, FL is essential and sufficient for development toward lymphoid restricted progenitors from a population of (c-kit+flt3+) multipotent short-term reconstituting progenitors.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Giovanna Del Pozzo ◽  
Dina Mascolo ◽  
Rossella Sartorius ◽  
Alessandra Citro ◽  
Pasquale Barba ◽  
...  

The ability of fd bacteriophage particles to trigger different arms of the immune system has been previously shown by us with particular emphasis on the ability of phages to raise CTL responses in vitro and in vivo. Here we show that fd virions in the absence of adjuvants are able to evoke a DTH reaction mediated by antigen specific CD8+ T cells. In addition, we analyzed the induction of CTL responses in mice depleted of CD4+ T cells, and we observed that short-term secondary CTL responses were induced in the absence of CD4+ T cells while induction of long-term memory CTLs required the presence of CD4+ T lymphocytes. These results examine the cellular mechanism at the basis of fd efficiency and provide new elements to further validate the use of fd particles for eliciting and monitoring antigen-specific CTLs.


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