The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts

Yhee, Ji Young; Yoon, Hong Yeol; Kim, Hyunjoon; Jeon, Sangmin; Hergert, Polla; Im, Jingtaek; Panyam, Jayanth; Kim, Kwangmeyung; Nho, Richard Seonghun

doi:10.2147/ijn.s138129

Cited by 22 publications

(12 citation statements)

References 38 publications

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“…The difference in the BSA-AuNCs internalization was correlated with more ECM production on nanofibers compared to TCPS. Previous studies also suggest the rapid and accelerated cellular internalizations of nanoparticles on ECM substrates compared to the flat surfaces [ 29 ]. These results are also supported by previous studies which show the role of cell cycle stages on nanoparticle internalizations.…”

Section: Resultsmentioning

confidence: 99%

Biomimetic polycaprolactone-chitosan nanofibrous substrate influenced cell cycle and ECM secretion affect cellular uptake of nanoclusters

Jhala

Rather

Kedaria

et al. 2019

Bioactive Materials

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Biomimetic cell culture substrates are developed as an alternative to the conventional substrates. They provide necessary biochemical and biophysical cues to the cells from their surrounding environment for their optimal growth, behaviour and physiology. Changes in physiology of cells growing on biomimetic substrate can essentially affect results of in vitro biological experiments such as drug cytotoxicity, nanoparticle internalization or signalling pathways. As majority of ECM proteins are fibrous in nature, nanofibrous scaffolds have more biomimicking properties. Therefore, in this study, we developed ECM mimicking polycaprolactone-chitosan nanofiber substrate and evaluated its effect on cell morphology, proliferation, cell cycle and ECM production. Further, cellular uptake of BSA-AuNCs has been assessed on conventional and biomimetic substrate in order to demonstrate the effect of these events on cellular properties. It was observed that the cells that were grown for 15 days on the nanofibers, had majority of cells in the proliferative phase of cell cycle compared to TCPS. Moreover, these cells showed extensive collagen and fibronectin production. Due to these conditions C3H10T1/2 cells displayed higher cell internalization of BSA-AuNCs. Overall, this study indicates that the nano-topographical and biochemical environment could alter the cell proliferative behaviour and ECM production, which affects the cell internalization of BSA-AuNCs. Also, PCL-chitosan nanofibrous substrate could be a better alternative to TCPS for cell culture studies.

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Section: Resultsmentioning

confidence: 99%

Biomimetic polycaprolactone-chitosan nanofibrous substrate influenced cell cycle and ECM secretion affect cellular uptake of nanoclusters

Jhala

Rather

Kedaria

et al. 2019

Bioactive Materials

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“…In the control, without HIFU exposure, Cy5.5-labeled DOX-CNPs (red colors) slowly bound to cell membranes after 10 min post-incubation and then they were internalized into the cytoplasm at up to 30 min, wherein the bright red colors of Cy5.5-labeled DOX-CNPs were clearly observed in the cytoplasm compartment of A549 cells. It is reported that CNPs show a fast uptake into cancer cells via diverse nanoparticle-derived endocytic pathways [ 42 , 43 , 44 ]. Interestingly, the HIFU-triggered cellular uptake of Cy5.5-labeled DOX-CNPs (red color) was clearly observed after 5 min of HIFU pre-treatment (destruction mode; power: 10 MHz, mechanical index: 0.235), compared to untreated Cy5.5-labeled DOX-CNPs.…”

Section: Resultsmentioning

confidence: 99%

Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

et al. 2020

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The dense extracellular matrix (ECM) in heterogeneous tumor tissues can prevent the deep tumor penetration of drug-loaded nanoparticles, resulting in a limited therapeutic efficacy in cancer treatment. Herein, we suggest that the deep tumor penetration of doxorubicin (DOX)-loaded glycol chitosan nanoparticles (CNPs) can be improved using high-intensity focused ultrasound (HIFU) technology. Firstly, we prepared amphiphilic glycol chitosan-5β-cholanic acid conjugates that can self-assemble to form stable nanoparticles with an average of 283.7 ± 5.3 nm. Next, the anticancer drug DOX was simply loaded into the CNPs via a dialysis method. DOX-loaded CNPs (DOX-CNPs) had stable nanoparticle structures with an average size of 265.9 ± 35.5 nm in aqueous condition. In cultured cells, HIFU-treated DOX-CNPs showed rapid drug release and enhanced cellular uptake in A549 cells, resulting in increased cytotoxicity, compared to untreated DOX-CNPs. In ECM-rich A549 tumor-bearing mice, the tumor-targeting efficacy of intravenously injected DOX-CNPs with HIFU treatment was 1.84 times higher than that of untreated DOX-CNPs. Furthermore, the deep tumor penetration of HIFU-treated DOX-CNPs was clearly observed at targeted tumor tissues, due to the destruction of the ECM structure via HIFU treatment. Finally, HIFU-treated DOX-CNPs greatly increased the therapeutic efficacy at ECM-rich A549 tumor-bearing mice, compared to free DOX and untreated DOX-CNPs. This deep penetration of drug-loaded nanoparticles via HIFU treatment is a promising strategy to treat heterogeneous tumors with dense ECM structures.

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“…The confocal microscope images of the VX2 tumor cells showed that the NIRF signal of the Cy5.5-CNPs in the cytoplasm was gradually increased by the treatment concentration of Cy5.5-CNPs at 24 h ( Figure 2 a). This is because the Cy5.5-CNPs could internalize into the cells via a nanoparticle-derived cellular uptake mechanism [ 38 , 39 ]. To evaluate the cytotoxicity of Cy5.5-CNPs and ICG-CNPs in the VX2 tumor cells, the cell viability of the VX2 tumor cells that were treated with CNPs, Cy5.5-CNPs, and ICG-CNPs for 24 h was measured using Cell Counting Kit-8 (CCK-8).…”

Section: Resultsmentioning

confidence: 99%

Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer

Rho

Yoon

et al. 2020

Pharmaceutics

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Theranostic nanoparticles can deliver therapeutic agents as well as diverse imaging agents to tumors. The enhanced permeation and retention (EPR) effect is regarded as a crucial mechanism for the tumor-targeted delivery of nanoparticles. Although a large number of studies of the EPR effect of theranostic nanoparticles have been performed, the effect of the change in the body size of the host on the EPR effect is not fully understood. In this regard, comparative research is needed on the behavior of nanoparticles in large animals for developing the nanoparticles to the clinical stage. In this study, we prepared fluorophore (indocyanine green (ICG) or cyanine 5.5 (Cy5.5))–conjugated glycol chitosan nanoparticles (CNPs) for comparing the tumor-targeting efficacy in VX2 tumor-bearing mouse and rabbit models. As expected, the CNPs formed nano-sized spherical nanoparticles and were stable for 8 days under aqueous conditions. The CNPs also exhibited dose-dependent cellular uptake into VX2 tumor cells without cytotoxicity. The half-life of the near-infrared fluorescence (NIRF) signals in the blood were 3.25 h and 4.73 h when the CNPs were injected into mice and rabbits, respectively. Importantly, the CNPs showed excellent tumor accumulation and prolonged biodistribution profiles in both the VX2 tumor-bearing mouse and rabbit models, wherein the tumor accumulation was maximized at 48 h and 72 h, respectively. Based on the excellent tumor accumulation of the CNPs, finally, the CNPs were used in the image-guided surgery of the rabbit orthotopic VX2 lung tumor model. The lung tumor tissue was successfully removed based on the NIRF signal from the CNPs in the tumor tissue. This study shows that CNPs can be potentially used for tumor theragnosis in small animals and large animals.

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The effects of collagen-rich extracellular matrix on the intracellular delivery of glycol chitosan nanoparticles in human lung fibroblasts

Cited by 22 publications

References 38 publications

Biomimetic polycaprolactone-chitosan nanofibrous substrate influenced cell cycle and ECM secretion affect cellular uptake of nanoclusters

Biomimetic polycaprolactone-chitosan nanofibrous substrate influenced cell cycle and ECM secretion affect cellular uptake of nanoclusters

Deep Tumor Penetration of Doxorubicin-Loaded Glycol Chitosan Nanoparticles Using High-Intensity Focused Ultrasound

Tumor-Targeting Glycol Chitosan Nanoparticles for Image-Guided Surgery of Rabbit Orthotopic VX2 Lung Cancer

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