Abstract:
:Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release. A series of BCPs were prepared through one-pot synthesis from clinically used small molecule anticancer drugs. The ring-opening reaction of drug-conjugated thiolactones releases mercapto groups via aminolysis by N-(3-aminopropyl)-imidazole, which further react with poly(ethylene glycol)-block-poly(pyridyldisulfide ethylmethacrylate) (PEG-PDSEMA) to produce imidazole and disulfide bonds-incorporated BCPs. Taking paclitaxel (PTX) for example, PTX BCPs exhibited high drug-loading content (>50%) and low critical micellization concentration (5 × 10-3 g/L), which can self-assemble into micellar nanoparticles in aqueous solution with a small size (∼40 nm). The nanoparticles showed high tumor accumulation and uniform distribution in hypopermeable tumors via systemic administration. Meanwhile, imidazole moieties endow nanoparticles tumor pH-sensitive charge transition from nearly neutral to positive, which promoted cellular internalization. Disulfide bonds can be cleaved by intracellular glutathione (GSH) of cancer cells, which accelerate the release of active PTX drug inside cells. Finally, highly aggressive murine breast cancer 4T1 tumor and hypopermeable human pancreatic adenocarcinoma BxPC3 tumor were completely ablated after treatment by PTX BCP nanoparticles. Consequently, the robust and facile preparation strategy based on thiolactone chemistry represents an efficient approach to construct multifunctional BCPs for better therapeutic efficacy via addressing multiple physiological barriers.
journal_name
Biomaterialsjournal_title
Biomaterialsauthors
Ke W,Yin W,Zha Z,Mukerabigwi JF,Chen W,Wang Y,He C,Ge Zdoi
10.1016/j.biomaterials.2017.11.006subject
Has Abstractpub_date
2018-02-01 00:00:00pages
261-274eissn
0142-9612issn
1878-5905pii
S0142-9612(17)30727-5journal_volume
154pub_type
杂志文章相关文献
BIOMATERIALS文献大全abstract::Chitin grafted with poly(acrylic acid) (chitin-PAA) was prepared with the aim of obtaining a hydrogel characteristic for wound dressing application. The chitin-PAA films were synthesized at various acrylic acid feed contents to investigate its effect on water sorption ability. Acrylic acid (AA) was first linked to chi...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2003.08.020
更新日期:2004-03-01 00:00:00
abstract::The ability to manipulate and control the surface properties, without altering the substrate properties, is of crucial importance in the designing of biomedical materials. In this work, surface-initiated atom transfer radical polymerization (ATRP) is employed to tailor the functionality of polycaprolactone (PCL) film ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2010.01.032
更新日期:2010-04-01 00:00:00
abstract::Gd3+-based contrast agents monopolize in the clinical MR imaging-based diagnosis of hepatic tumors, however, the inherent toxicity by the released Gd3+-ions triggered an urgent demand for safer alternatives. Here, we demonstrate hollow manganese silicate nanoparticles (HMS), which exert burst-release of Mn2+-ions by s...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2019.119600
更新日期:2020-02-01 00:00:00
abstract::Topographical cues, independent of biochemistry, generated by the extracellular matrix may have significant effects upon cellular behavior. Studies have documented that substratum topography has direct effects on the ability of cells to orient themselves, migrate, and produce organized cytoskeletal arrangements. Basem...
journal_title:Biomaterials
pub_type: 杂志文章,评审
doi:10.1016/s0142-9612(98)00209-9
更新日期:1999-03-01 00:00:00
abstract::Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form micelles, which act as nanosized photosensitizing agents for photodynamic therapy (PDT) and further encapsulate hydrophobic drugs. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photod...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2009.03.048
更新日期:2009-07-01 00:00:00
abstract::The development of biocompatible photopolymerizing polymers for biomedical and tissue engineering applications has the potential to reduce the invasiveness and cost of biomaterial implants designed to repair or augment tissues. However, more information is needed about the cellular toxicity of the compounds and initia...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.04.024
更新日期:2005-04-01 00:00:00
abstract::A lipid/calcium/phosphate (LCP) nanoparticle (NP) formulation (particle diameter ∼25 nm) with superior siRNA delivery efficiency was developed and reported previously. Here, we describe the successful formulation of (111)In into LCP for SPECT/CT imaging. Imaging and biodistribution studies showed that, polyethylene gl...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2014.02.030
更新日期:2014-05-01 00:00:00
abstract::A technique for preparing micropatterns and gradients of proteins on polymeric substrates has been developed in this work. Peroxides were generated on the substrate surface by UV preirradiation and they initiated graft polymerization of acrylic acid (AA) onto the surface upon a second UV irradiation. Micropatterns and...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.05.004
更新日期:2005-05-01 00:00:00
abstract::Nanobubbles, as a kind of new ultrasound contrast agent (UCAs), have shown promise to penetrate tumor vasculature to allow for targeted imaging. However, their inherent physical instability is an ongoing concern that could weaken their imaging ability with ultrasound. Gas vesicles (GVs), which are genetically encoded,...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2020.119803
更新日期:2020-04-01 00:00:00
abstract::The standard solution-depletion method is implemented with SDS-gel electrophoresis as a multiplexing, separation-and-quantification tool to measure competition between two proteins (i and j) for adsorption to the same hydrophobic adsorbent particles (either octyl sepharose or silanized glass) immersed in binary-protei...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2009.08.016
更新日期:2009-11-01 00:00:00
abstract::As a chronic and lifelong disease, obesity not only significant impairs health but also dramatically shortens life span (at least 10 years). Obesity requires a life-long effort for the successful treatment because a number of abnormalities would appear in the development of obesity. Nanomaterials possess large specifi...
journal_title:Biomaterials
pub_type: 杂志文章,评审
doi:10.1016/j.biomaterials.2019.119474
更新日期:2019-12-01 00:00:00
abstract::Biological processes are of great significance for the normal physiological functions of living organisms and closely related to the health. Monitoring of biological processes and diagnosis of diseases based on fluorescent techniques would provide comprehensive insight into mechanism of life and pathogenesis of diseas...
journal_title:Biomaterials
pub_type: 杂志文章,评审
doi:10.1016/j.biomaterials.2017.09.004
更新日期:2017-11-01 00:00:00
abstract::Construction of bio-mimetic well-organized three-dimensional (3D) tissue with various cells in vitro is one of the ultimate goals of tissue engineering. In particular, fabrication of vasculature in 3D tissue is one of the most important tasks in tissue engineering, because a vascular network is indispensable for almos...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2012.10.009
更新日期:2013-01-01 00:00:00
abstract::Reactive oxygen species (ROS) have been shown to play crucial roles in regulating various cellular functions, e.g. focal adhesion (FA) dynamics and cell migration upon growth factor stimulation. However, it is not clear how ROS are regulated at subcellular FA sites to impact cell migration. We have developed a biosens...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.01.092
更新日期:2013-05-01 00:00:00
abstract::Delivery of polynucleotide-based therapeutics into target cells involves interactions with glycosaminoglycan chains that are located on cell membrane milieu. Mechanisms governing glycosaminoglycan-mediated changes in the nanoparticulate structures of polymer-polynucleotide complexes are unknown, and cannot be fully el...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2017.11.037
更新日期:2018-02-01 00:00:00
abstract::Synthesis and characterization of cinnamated Type I collagen and its related mechanical properties after photomediated crosslinking were investigated in detail. Using an EDC/NHS conjugation method, collagen was chemically modified to incorporate a photosensitive cinnamate moiety. The cinnamated collagen was fully char...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.10.017
更新日期:2005-06-01 00:00:00
abstract::Skeletal muscle is a highly organized tissue in which the extracellular matrix (ECM) is composed of highly-aligned cables of collagen with nanoscale feature sizes, and provides structural and functional support to muscle fibers. As such, the transplantation of disorganized tissues or the direct injection of cells into...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.10.067
更新日期:2014-02-01 00:00:00
abstract::We report a novel silk-gold nanocomposite based nerve conduit successfully tested in a neurotmesis grade sciatic nerve injury model in rats over a period of eighteen months. The conduit was fabricated by adsorbing gold nanoparticles onto silk fibres and transforming them into a nanocomposite sheet by electrospinning w...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2015.04.047
更新日期:2015-09-01 00:00:00
abstract::The management of trauma-associated nerve defects is difficult because of the absence of autologous donor motor or sensory nerves. Pre-clinical development and clinical experience has shown that damaged nerves can be surgically repaired using a tubular conduit interposed across the defect. Acceptable patient outcomes ...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2007.08.023
更新日期:2008-01-01 00:00:00
abstract::The blood-brain barrier (BBB) prevents entry of neurotoxic substances but also that of drugs into the brain. Here, the paracellular barrier is formed by tight junctions (TJs) with claudin-5 (Cldn5) being the main sealing constituent. Transient BBB opening by targeting Cldn5 could improve paracellular drug delivery. Th...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2018.01.028
更新日期:2018-04-01 00:00:00
abstract::A tissue-engineered bone has become a viable alternative to autologous bone for bone augmentation in atrophy alveolar ridge. The aim of the present study was to evaluate porous beta-tricalcium phosphate (beta-TCP) combined with autologous osteoblasts to augment edentulous alveolar ridge in a canine model. Autologous o...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2008.12.067
更新日期:2009-05-01 00:00:00
abstract::Achieving and maintaining safe and reliable lineage specific differentiation of stem cells is important for clinical translation of tissue engineering strategies. In an effort to circumvent the multitude of problems arising from the usage of growth factors and growth factor delivery systems, we have explored the use o...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2016.09.029
更新日期:2016-12-01 00:00:00
abstract::There is great interest for developing poly(lactide-co-glycolide) (PLGA) based particles for targeted delivery and controlled release of encapsulated biological molecules. These PLGA particles can be used to deliver proteins, small molecule drugs and nucleotides. Furthermore, it has been shown that the co-encapsulatio...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2013.01.032
更新日期:2013-04-01 00:00:00
abstract::We have prepared unique macroporous and ordered dextran-based hydrogels using a single-step biocatalytic transesterification reaction between dextran and divinyladipate in neat dimethylsulfoxide. These hydrogels show a unimodal distribution of interconnected pores with average diameters from 0.4 to 2.0 microm dependin...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2004.11.051
更新日期:2005-08-01 00:00:00
abstract::The search for a cell-supporting scaffold with controlled topography and surface chemistry is a constant topic within tissue engineering. Here we have employed M13 phages, which are genetically modifiable biological nanofibers (∼ 880 nm long and ∼ 6.6 nm wide) non-toxic to human beings, to form films for supporting th...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2011.03.030
更新日期:2011-07-01 00:00:00
abstract::A simple and sensitive method for the quantitative determination of solid-supported primary and/or secondary amino groups using commercially available reagents is described. The solid supports are treated in an aqueous environment with either 2-iminothiolane (ITL) or sulpho-succinimidyl-3-(4-hydroxyphenyl)propionate (...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/0142-9612(94)90054-x
更新日期:1994-03-01 00:00:00
abstract::Following our recent report of attractive antibacterial properties of a designed amphiphilic peptide, A(9)K, we have investigated its antitumor activities by examining the modes of its action against different mammalian cell types. The peptide strongly inhibited the growth of cancerous HeLa cells and human promyelocyt...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2012.12.039
更新日期:2013-04-01 00:00:00
abstract::Bioabsorbable internal fixation devices were introduced clinically in the treatment of fractures and osteotomies of the extremities at the Department of Orthopaedics and Traumatology, Helsinki University, in 1984. Since November 5, 1984, a total of 3200 patients were managed using bone or ligament fixation devices mad...
journal_title:Biomaterials
pub_type: 杂志文章,评审
doi:10.1016/s0142-9612(00)00128-9
更新日期:2000-12-01 00:00:00
abstract::A series of polymer and copolymer networks with varying hydrophilicity and distribution of the hydrophilic groups was synthesized and biologically tested with monolayer culture of human chondrocytes in vitro. Cell viability (MTT), proliferation (BrdU incorporation) and aggrecan expression (PG ELISA) were quantified at...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/j.biomaterials.2005.07.030
更新日期:2006-03-01 00:00:00
abstract::The use of a composite graft of bovine trabecular demineralized bone matrix (DBM) and perichondrium has been found a reliable method for in vivo generation of cartilage. In the present study, the mechanism whereby this commercially available matrix increases cartilage formation was investigated. First, the time course...
journal_title:Biomaterials
pub_type: 杂志文章
doi:10.1016/s0142-9612(98)00165-3
更新日期:1999-02-01 00:00:00