Abstract:
:A chitosan oligosaccharide (CSO)-indomethacin (IDM) conjugate (CI) was synthesized to fabricate chemosensitizing nanoparticles (NPs) for tumor-targeted drug delivery. IDM was conjugated to a CSO backbone via amide bond formation, of which successful synthesis was confirmed by proton-nuclear magnetic resonance analyses. Doxorubicin (DOX)-loaded CI (CI10/DOX; CI:DOX=10:1 [w/w]) NPs with <75nm of mean diameter, polydispersity index of ∼0.2, and positive zeta potential were prepared. The release of DOX from the NPs was enhanced at acidic pH (pH 5.5 and 6.8) compared to physiological pH (pH 7.4). The release of IDM increased in the presence of A549 cell lysates. In A549 cells (human lung carcinoma cells), more efficient cellular uptake of CI10/DOX NPs than that of free DOX was observed by using confocal laser scanning microscopy and flow cytometry. The in vitro cytotoxicity of CI10/DOX NPs in A549 cells was higher than those of free DOX and CI NPs with free DOX groups. In vivo pharmacokinetic studies after intravenous administration in rats showed significantly lower clearance of DOX from NPs compared with the free DOX group. Tumor targetability of the developed CI NPs was also verified by a real-time optical imaging study. In summary, the chemosensitizing CI/DOX NP with enhanced anticancer activity, prolonged blood circulation, and passive tumor targeting can be a promising anticancer drug delivery system for tumor-targeted therapy. STATEMENT OF SIGNIFICANCE:Chemosensitizing nanoparticles (NPs) based on amphiphilic chitosan oligosaccharide-indomethacin (CSO-IDM; CI) conjugate were developed for tumor-targeted delivery of doxorubicin (DOX). IDM was introduced to the CSO backbone as a hydrophobic residue to synthesize an amphiphilic conjugate and a chemosenstizer of DOX for improving antitumor efficacies. IDM, conjugated to CSO, may inhibit the efflux of cellular uptaken DOX via multidrug resistance-associated protein (MRP) and subsequently augment the anti-proliferation potentials of DOX in A549 cells (MRP-expressed human lung cancer cells). Chemosensitizing properties of developed CI NPs were assessed in cell culture models and the tumor targetability of CI/DOX NPs was demonstrated in A549 tumor-xenografted mouse model by a real-time optical imaging. Developed CI NPs can be used as a multifunctional nanosystem for the therapy of MRP-expressed cancers.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Lee JY,Termsarasab U,Lee MY,Kim DH,Lee SY,Kim JS,Cho HJ,Kim DDdoi
10.1016/j.actbio.2017.05.012subject
Has Abstractpub_date
2017-07-15 00:00:00pages
262-273eissn
1742-7061issn
1878-7568pii
S1742-7061(17)30293-3journal_volume
57pub_type
杂志文章abstract::Cationic polymer-based vectors have been considered a promising strategy in gene therapy area due to their inherent ability to condense genetic material and successfully transfect cells. However, they usually exhibit high cytotoxicity. In this work, it is proposed the use of a tailor-made gene carrier based on a tri-b...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.10.015
更新日期:2017-01-01 00:00:00
abstract::Semiconducting nanoparticles, more commonly known as quantum dots, possess unique size and shape dependent optoelectronic properties. In recent years, these unique properties have attracted much attention in the biomedical field to enable real-time tissue imaging (bioimaging), diagnostics, single molecule probes, and ...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2019.05.022
更新日期:2019-08-01 00:00:00
abstract::Small intestine submucosa (SIS) has emerged as one of a number of naturally derived extracellular matrix (ECM) biomaterials currently in clinical use. In addition to clinical applications, ECM materials form the basis for a variety of approaches within tissue engineering research. In our preliminary work it was found ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.08.024
更新日期:2014-12-01 00:00:00
abstract::The surface of an implant device can be modified by immobilizing biological molecules on it to improve its integration into the host tissue. We have previously demonstrated that enzymatically tailored plant pectins are promising nanocoatings for biomaterials. This study investigates whether a coating of modified hairy...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.03.031
更新日期:2009-09-01 00:00:00
abstract::Gene delivery from a substrate depends, in part, on the vector-nucleic acid complex that is bound to the surface and the cell adhesive properties of the surface. Here, we present a method to deliver patterns of small interfering RNA (siRNA) that capitalize on a forward transfection method (transfection by introducing ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.01.004
更新日期:2009-06-01 00:00:00
abstract::Pressure ulcers are a significant healthcare concern, especially for elderly populations. Our work served to ameliorate the chronicity of these ulcers by addressing ischemia-reperfusion injury mediated by neutrophils and the concomitant loss of vasculature in these wounds. To this end, chitosan scaffolds loaded with b...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.03.002
更新日期:2009-07-01 00:00:00
abstract::There is increasing interest in the development of new tissue engineering strategies to deliver cells and bioactive agents encapsulated in a biodegradable matrix through minimally invasive procedures. The present work proposes to combine chitosan-beta-glycerophosphate salt formulations with bioactive glass nanoparticl...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.08.006
更新日期:2009-01-01 00:00:00
abstract::Chemokines are guiding cues for directional trafficking of mesenchymal stem cells (MSC) upon injury and local chemokine delivery at injury sites is an up-to-date strategy to potentiate and prolong recruitment of MSC. In this study we present the chemokine CCL25, also referred to as thymus-expressed chemokine, to mobil...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.01.036
更新日期:2018-03-15 00:00:00
abstract::Natural silk fiber spun by the silkworm Bombyx mori is widely used not only for textile materials, but also for biofunctional materials. In the present study, we genetically engineered an advanced silk material, named hSFSV, using a transgenic silkworm, in which the recombinant human acidic fibroblast growth factor (h...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.06.031
更新日期:2014-12-01 00:00:00
abstract:UNLABELLED:Epithelial cellular heterogeneity has been observed in pathological tissues with abnormal matrix stiffness and cells cultured on rigid substrates. However, it remains unclear how matrix stiffness influences cellular heterogeneity formation in multi-cellular population. Here, we demonstrated that cellular het...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.05.025
更新日期:2016-09-01 00:00:00
abstract::Multilaminated controlled release devices were formed through photopolymerization techniques to produce hydrogels with spatially varying solute loadings and network structures composed of poly(hydroxyl ethyl methacrylate) (PHEMA) and poly(ethylene glycol) (PEG). Using low molecular weight fluorescent dyes as model dru...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2006.11.006
更新日期:2007-07-01 00:00:00
abstract::Stimuli responsive polyelectrolyte nanoparticles have been developed for chemo-photothermal destruction of breast cancer cells. This novel system, called layer by layer Lipo-graph (LBL Lipo-graph), is composed of alternate layers of graphene oxide (GO) and graphene oxide conjugated poly (l-lysine) (GO-PLL) deposited o...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.10.040
更新日期:2018-01-01 00:00:00
abstract::Magnesium (Mg) medical devices are currently being marketed for orthopedic applications and have a complex degradation process which includes the evolution of hydrogen gas (H2). The effect of H2 exposure on relevant cell types has not been studied; and the concentration surrounding degrading Mg devices has not been qu...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.04.032
更新日期:2018-06-01 00:00:00
abstract::Antimicrobial peptides (AMP) are powerful components of the innate immune system, as they display wide activity spectrum and low tendency to induce pathogen resistance. Hence, the development of AMP-based coatings is a very promising strategy to prevent biomaterials-associated infections. This work aims to investigate...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.12.001
更新日期:2019-01-15 00:00:00
abstract::Globally, chronic wounds impose a notable burden to patients and healthcare systems. Such skin wounds are readily subjected to bacteria that provoke inflammation and hence challenge the healing process. Furthermore, bacteria induce infection impeding re-epithelialization and collagen synthesis. With an estimated globa...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2020.02.022
更新日期:2020-04-15 00:00:00
abstract::After skin tissue injury or pathological removal, vascularization timing is paramount in graft survival. As full thickness skin grafts often fail to become perfused over larger surfaces, split-thickness grafts are preferred and can be used together with biomaterials, which themselves are non-angiogenic. One way of pro...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.01.050
更新日期:2020-04-01 00:00:00
abstract::This study investigates the bone and tissue response to degrading magnesium pin implants in the growing rat skeleton by continuous in vivo microfocus computed tomography (μCT) monitoring over the entire pin degradation period, with special focus on bone remodeling after implant dissolution. The influence of gas releas...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.11.008
更新日期:2012-03-01 00:00:00
abstract::Poly(ethylene glycol) (PEG) can be functionalized and modified with various moieties allowing for a multitude of cross-linking chemistries. Here, we investigate how vinyl sulfone, acrylate, and maleimide functional end groups affect hydrogel formation, physical properties, viability of encapsulated cells, post-polymer...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.12.007
更新日期:2018-02-01 00:00:00
abstract::The aim of this study was to fabricate a fibrous scaffold that closely resembled the micro-structural architecture and mechanical properties of collagen fibres found in the anterior cruciate ligament (ACL). To achieve this aim, fibrous scaffolds were made by electrospinning L-lactide based polymers. L-Lactide was chos...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.07.012
更新日期:2012-11-01 00:00:00
abstract:UNLABELLED:The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly alloca...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.09.026
更新日期:2015-12-01 00:00:00
abstract::Titanium oxide coatings have been shown to exhibit desirable properties as biocompatible coatings. We report on the quantitative microstructure characterization and deformation behavior of TiO(2) nanotubes on Ti substrate. Nanotubes were processed using anodic oxidation of Ti in a NaF electrolyte solution. Characteriz...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2006.08.004
更新日期:2007-05-01 00:00:00
abstract:UNLABELLED:Chondrocyte dedifferentiation presents a major barrier in engineering functional cartilage constructs. To mitigate the effects of dedifferentiation, this study employed a post-expansion aggregate culture step to enhance the chondrogenic phenotype of passaged articular chondrocytes (ACs) before their integrat...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.07.044
更新日期:2016-10-01 00:00:00
abstract::Functional and perfusable vascular network formation is critical to ensure the long-term survival and functionality of engineered tissues after their transplantation. Although several vascularization strategies have been reviewed in past, the significance of microvessel organization in three-dimensional (3D) scaffolds...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2019.03.016
更新日期:2019-09-01 00:00:00
abstract::This study demonstrated that the surface crystallinity of carbon nanostructures is an additional independent factor that should be considered for the inhibition of cancer proliferation without activating reactive oxygen species (ROS). In addition, cytotoxic evaluation of both proliferating cancer cells and fully diffe...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.05.013
更新日期:2012-09-01 00:00:00
abstract::Due to the prevalence of problems caused by wear particles, the reduced durability of total joint replacements is well documented. The characterization of wear debris enables the size and morphology of these wear particles to be measured and provides an assessment of the biological response in vivo. However, the impac...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.07.039
更新日期:2013-12-01 00:00:00
abstract::Intervertebral disc (IVD) disorders and age-related degeneration are believed to contribute to lower back pain. There is significant interest in cell-based strategies for regenerating the nucleus pulposus (NP) region of the disc; however, few scaffolds have been evaluated for their ability to promote or maintain an im...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.11.013
更新日期:2014-03-01 00:00:00
abstract::Polymeric fibrous scaffolds have been considered as replacements for load-bearing soft tissues, because of their ability to mimic the microstructure of natural tissues. Poor toughness of fibrous materials results in failure, which is an issue of importance to both engineering and medical practice. The toughness of fib...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.02.046
更新日期:2013-07-01 00:00:00
abstract::Damages in pelvic floor muscles often cause dysfunction of the entire pelvic urogenital system, which is clinically challenging. A bioengineered skeletal muscle construct that mimics structural and functional characteristics of native skeletal muscle could provide a therapeutic option to restore normal muscle function...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.12.012
更新日期:2021-02-01 00:00:00
abstract::Lanreotide (LT), a synthetic analog of somatostatin, has been demonstrated to specifically bind to somatostatin receptors (SSTRs), which are widely overexpressed in several types of cancer cells. In this study, we incorporated a chemotherapeutic agent, methotrexate (MTX), and a photosensitizer material, polyaniline (P...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.12.033
更新日期:2018-03-01 00:00:00
abstract::Implant-associated infections is one of the most challenging post-operative complications in bone-related implantations. To tackle this clinical issue, we developed a low-cost and durable surface coating for medical grade titanium implants that uses positively charged silane molecules. The in vitro antimicrobial tests...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.07.040
更新日期:2020-09-15 00:00:00