Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Xiang, Shengnan; Sarem, Melika; Shah, Samveg; Shastri, V. Prasad

doi:10.1002/smll.201704245

Cited by 21 publications

(17 citation statements)

References 55 publications

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“…It has been suggested that the presence of cholesterol and poly-saturated fatty acids in the lipid bilayer increases the stiffness [45]. We have recently shown that cell plasma membrane lipid bilayer composition is altered by lipid transfer, and this impacts the deformability of cell membrane [46]. Since several genes associated with lipid transfer and lipid storage were downregulated in low -ACNs, we investigated if these differences at the gene expression level translate into changes in the stiffness of cells.…”

Section: Resultsmentioning

confidence: 99%

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis

et al. 2019

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BackgroundAlthough mesenchymal stem/stromal cell (MSC) chondrogenic differentiation has been thoroughly investigated, the rudiments for enhancing chondrogenesis have remained largely dependent on external cues. Focus to date has been on extrinsic variables such as soluble signals, culture conditions (bioreactors), and mechanical stimulation. However, the role of intrinsic mechanisms of MSC programming-based mechanobiology remains to be explored. Since aggregation of MSCs, a prerequisite for chondrogenesis, generates tension within the cell agglomerate, we inquired if the initial number of cells forming the aggregate (aggregate cell number (ACN)) can impact chondrogenesis.MethodsAggregates of varying ACN were formed using well-established centrifugation approach. Progression of chondrogenic differentiation in the aggregates was assessed over 3 weeks in presence and absence of transforming growth factor-beta 1 (TGF-β1). Mechanical properties of the cells were characterized using high-throughput real-time deformability cytometry (RT-DC), and gene expression was analyzed using Affymetrix gene array. Expression of molecular markers linked to chondrogenesis was assessed using western blot and immunofluorescence.ResultsReducing ACN from 500 k to 70 k lead to activation and acceleration of the chondrogenic differentiation, independent of soluble chondro-inductive factors, which involves changes to β-catenin-dependent TCF/LEF transcriptional activity and expression of anti-apoptotic protein survivin. RT-DC analysis revealed that stiffness and size of cells within aggregates are modulated by ACN. A direct correlation between progression of chondrogenesis and emergence of stiffer cell phenotype was found. Affymetrix gene array analysis revealed a downregulation of genes associated with lipid synthesis and regulation, which could account for observed changes in cell stiffness. Immunofluorescence and western blot analysis revealed that increasing ACN upregulates the expression of lipid raft protein caveolin-1, a β-catenin binding partner, and downregulates the expression of N-cadherin. As a demonstration of the relevance of these findings in MSC-based strategies for skeletal repair, it is shown that implanting aggregates within collagenous matrix not only decreases the necessity for high cell numbers but also leads to marked improvement in the quality of the deposited tissue.ConclusionsThis study presents a simple and donor-independent strategy to enhance the efficiency of MSC chondrogenic differentiation and identifies changes in cell mechanics coincident with MSC chondrogenesis with potential translational applications.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1103-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis

et al. 2019

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“…It has been reported that genetic changes of Cav1 might modify the risk for breast cancer,151 and Cav1 acts both as a tumor suppressor as well as an oncogene, and plays a key role in breast cancer tumorigenesis 152. In addition to breast cancer carcinogenic process, Cav1 is also associated with lung cancer,153,154 colorectal cancer,155 gastric cancer,156,157 cervical cancer,158 hepatocellular carcinoma,159 pancreatic cancer,160 bladder cancer,161 pulmonary hypertension,162–164 virus infection,165,166 cardiovascular disease,167,168 diabetes mellitus,169 nanomedicines endocytosis170 and lipodystrophy 171. Besides, it has been reported that caveo-lin-2 (Cav2) can also mediate the initiation and development of breast cancer 26…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

<p>Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment</p>

Qian

Pan

Huang

et al. 2019

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Human breast cancer is one of the most frequent cancer diseases and causes of death among female population worldwide. It appears at a high incidence and has a high malignancy, mortality, recurrence rate and poor prognosis. Caveolin-1 (Cav1) is the main component of caveolae and participates in various biological events. More and more experimental studies have shown that Cav1 plays a critical role in the progression of breast cancer including cell proliferation, apoptosis, autophagy, invasion, migration and breast cancer metastasis. Besides, Cav1 has been found to be involved in chemotherapeutics and radiotherapy resistance, which are still the principal problems encountered in clinical breast cancer treatment. In addition, stromal Cav1 may be a potential indicator for breast cancer patients' prognosis. In the current review, we cover the state-of-the-art study, development and progress on Cav1 and breast cancer, altogether describing the role of Cav1 in breast cancer progression and application in clinical treatment, in the hope of providing a basis for further research and promoting CAV1 gene as a potential target to diagnose and treat aggressive breast cancers.

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“…MMP-12-siRNA-CPA NPs ameliorate HFD feeding-induced hepatic steatosis, adiposity and systemic in ammation. Given that impaired insulin sensitivity facilitates the pathological progression of hepatic steatosis, adiposity and systemic in ammation 28 , we next examined the effects of MMP-12-siRNA-CPA NPs on these pathological parameters in HFD-fed mice. As shown in Fig.5a ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Delivery of MMP-12 siRNA with a Nanocarrier Improves the Homeostasis of the Small Intestine and Metabolic Dysfunction in High-Fat Diet Feeding-Induced Obese Mice

Song

Zhang

Tao

et al. 2020

Preprint

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The changes of small intestinal homeostasis have been recognized to contribute essentially to the obese development. However, the core small intestinal regulator which mediates overnutrient impacts on the homeostasis of the small intestines remains elusive. Here, we identify the MMP-12 as such a responsive factor in mouse small intestines. Taking advantages of the nano delivery system, we demonstrate that small intestine-specific MMP-12 knockdown alleviates high-fat diet feeding-induced metabolic disorders and improves intestinal homeostasis in mice, including a significant decrease in lipid transportation, bile acid reabsorption, and inflammation. In parallel, the small intestinal integrity is recovered and the gut microbiota composition is reversed towards that under normal diet feeding. Mechanistically, MMP-12, differing from its traditional elastolytic function, acts as a transcriptional factor to activate Fabp4 transcription through epigenetic modification. In translational medicine, clinical applications of our nanosystem and therapeutic interventions targeting MMP-12 will benefit patients with obesity and associated diseases.

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Liposomal Treatment of Cancer Cells Modulates Uptake Pathway of Polymeric Nanoparticles by Altering Membrane Stiffness

Cited by 21 publications

References 55 publications

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis

Cell number in mesenchymal stem cell aggregates dictates cell stiffness and chondrogenesis

<p>Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment</p>

Delivery of MMP-12 siRNA with a Nanocarrier Improves the Homeostasis of the Small Intestine and Metabolic Dysfunction in High-Fat Diet Feeding-Induced Obese Mice

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