The Influence of Drug Loading on Caveolin-1 Mediated Intracellular Internalization of Doxorubicin Nanomicelles in vitro

Nehoff, Hayley

doi:10.4172/2157-7439.1000197

Cited by 10 publications

(6 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is consistent with the lower in vitro activity of nanocarriers [ 19 ]. Micelles are internalized into the cells via endocytosis [ 20 ], a time and energy-dependent process in contrast to the simple diffusion of the free complex. MCF-7 cells ( Figure 3 A) appeared more resistant to the cytotoxic effect of the curcumin complexes and micelles when compared to MDA-MB-231 and 4T1 cells and showed that both CD and SMA–CD had no significant difference in their cytotoxic profile after 48 h incubation ( Table 2 , IC 50 of 3.373 µM and 3.370 µM, respectively).…”

Section: Resultsmentioning

confidence: 99%

Curcumin–Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer

et al. 2018

View full text Add to dashboard Cite

Breast cancer is the most common cancer diagnosed among females worldwide. Although breast cancer survival has largely improved in the past 30 years, it remains highly heterogeneous in its response to treatment. Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks the expression of the estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor-2 (Her2). While TNBC may initially be responsive to chemotherapy, recurrence and subsequent high mortality rates are frequently reported. Studies have shown curcumin and its derivatives to be effective against TNBC cell lines in vitro. To improve its anti-cancer effects, we have synthesized Fe3+–curcumin (Fe–Cur3) and Cu2+–curcumin (CD) complexes and investigated them experimentally. Further, CD was encapsulated into a poly(styrene)-co-maleic acid (SMA) micelle to enhance its stability. We assessed the cytotoxicity of these formulations both in vitro and in vivo. SMA–CD demonstrated dose-dependent cytotoxicity and abolished TNBC tumor growth in vivo. The encapsulation of the curcumin–copper complex improved its anti-cancer activity without overt adverse effects in a murine model of TNBC. These results provide evidence and insights into the value of nanoformulations in enhancing drug-delivery and increasing the potential therapeutic efficacy of curcumin derivatives.

show abstract

Section: Resultsmentioning

confidence: 99%

Curcumin–Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Further, the recycling of transmembrane proteins may also be influenced by interaction with proteins like Caveolin 1, among others 64 . Interestingly, constitutive in vitro expression of Caveolin 1 is markedly higher in MDA-MB-231 cells than in many other tumor cell lines 65 , 66 , suggesting its potential for a greater influence in this cell line. Similarly, upregulation of exocytotic release of exosomes or vesicles from tumor cells during hypoxia is known to play a significant role in tumor development and signaling 37 , 67 , with implications for altered or upregulated exocytosis.…”

Section: Discussionmentioning

confidence: 95%

Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

Brownlee

Seib

2018

Sci Rep

View full text Add to dashboard Cite

Breast cancer cells adapt to the hypoxic tumoral environment by undergoing changes in metabolism, cell signalling, endo-lysosomal receptor uptake and recycling. The resulting hypoxic cell phenotype has the potential to undermine the therapeutic efficacy of nanomedicines designed for endocytic uptake and specific intracellular trafficking. The aim of this study was to examine the impact of hypoxia and simulated reperfusion on the in vitro uptake and release of nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal changes in the hypoxic circuit (e.g. HIF-1α expression). The preconditioned cells were then dosed with nanoparticles for 45 or 180 minutes emulating nanomedicine access following tumor reperfusion. Hypoxic preconditioning significantly increased nanoparticle retention by up to 10% when compared to normoxic cultures, with the greatest relative difference between normoxic and hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies indicated that the preconditioned cells had a significantly increased nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were able to show that hypoxic preconditioning regulates both the endocytosis and exocytosis of nanomedicines in human breast cancer cells.

show abstract

“…SMA has demonstrated a potential for oral delivery and is proven to traverse intestinal barriers with appropriate therapeutic outcomes [32]. The SMA micellar system was used previously for the oral delivery of anticancer agents [32,33]. The SMA system is especially well-suited for different applications, due to the low cost of the polymer, simplicity of the preparation process, and the loading can be controlled (up to 40% w/w) [33].…”

Section: Introductionmentioning

confidence: 99%

Oral Insulin Delivery Using Poly (Styrene Co-Maleic Acid) Micelles in a Diabetic Mouse Model

et al. 2020

View full text Add to dashboard Cite

The oral delivery of insulin is a convenient and safe physiological route of administration for management of diabetes mellitus. In this study, we developed a poly-(styrene-co-maleic acid) (SMA) micellar system for oral insulin delivery to overcome the rapid degradation of insulin in the stomach, improve its absorption in the intestine, and provide a physiologically-relevant method of insulin to reach portal circulation. The insulin was encapsulated into SMA micelles in a pH-dependent process. The charge and size of the nanoparticles were determined by dynamic light scattering. The insulin loading of the nanoparticles was measured by HPLC. The transport of the SMA-insulin through biological membranes was assessed in vitro using Caco-2 cells, ex vivo rat intestinal section, and in vivo in a streptozotocin-induced diabetes mouse model. SMA-insulin micelles were negatively charged and had a mean diameter of 179.7 nm. SMA-insulin efficiently stimulated glucose uptake in HepG-2 hepatic cells and was transported across the Caco-2 epithelial cells in vitro by 46% and ex vivo across intestinal epithelium by 22%. The animal studies demonstrated that orally-administered SMA-insulin can produce a hypoglycemic effect up to 3 h after administration of one dose. Overall, our results indicate that SMA micelles are capable of the oral delivery of bioactive compounds like insulin and can be effective tools in the management of diabetes.

show abstract

The Influence of Drug Loading on Caveolin-1 Mediated Intracellular Internalization of Doxorubicin Nanomicelles in vitro

Cited by 10 publications

References 38 publications

Curcumin–Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer

Curcumin–Copper Complex Nanoparticles for the Management of Triple-Negative Breast Cancer

Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by human breast cancer cells

Oral Insulin Delivery Using Poly (Styrene Co-Maleic Acid) Micelles in a Diabetic Mouse Model

Contact Info

Product

Resources

About