Abstract:
UNLABELLED:The design of polymeric nanoparticles for gene therapy requires engineering of polymer structure to overcome multiple barriers, including prolonged colloidal stability during formulation and application. Poly(β-amino ester)s (PBAEs) have been shown effective as polymeric vectors for intracellular DNA delivery, but limited studies have focused on polymer modifications to enhance the stability of PBAE/DNA polyplexes. We developed block copolymers consisting of PBAE oligomer center units and poly(ethylene glycol) (PEG) end units. We fabricated a library of PEG-PBAE polyplexes by blending PEGylated PBAEs of different PEG molecular weights and non-PEGylated PBAEs of different structures at various mass ratios of cationic polymer to anionic DNA. Non-PEGylated PBAE polyplexes aggregated following a 24h incubation in acidic and physiological buffers, presenting a challenge for therapeutic use. In contrast, among 36 PEG-PBAE polyplex formulations evaluated, certain polyplexes maintained a small size under these conditions. These selected polyplexes were further evaluated for transfection in human small cell lung cancer cells (H446) in the presence of serum, and the best formulation transfected ∼40% of these hard-to-transfect cells while preventing polymer-mediated cytotoxicity. When PEG-PBAE polyplex delivered Herpes simplex virus thymidine kinase plasmid in combination with the prodrug ganciclovir, the polyplexes killed significantly more H446 cancer cells (35%) compared to healthy human lung fibroblasts (IMR-90) (15%). These findings indicate that PEG-PBAE polyplexes can maintain particle stability without compromising their therapeutic function for intracellular delivery to human small cell lung cancer cells, demonstrate potential cancer specificity, and have potential as safe materials for small cell lung cancer gene therapy. STATEMENT OF SIGNIFICANCE:Many natural and synthetic biomaterials have been investigated as non-viral vectors to deliver nucleic acids for cancer therapy. However, there are multiple hurdles to successful transfection including achieving particle stability, efficient delivery to cancer cells, and low cytotoxicity. In particular, engineering the physicochemical surface properties of a nanoparticle to improve stability is often offset by a decrease in the cellular entry and transfection efficiency. We developed stable polymeric nanoparticles that demonstrate high transfection efficiency by modifying synthetic biodegradable cationic polymers and engineering nanoparticle formulations using a combinatorial approach. The results of this study show the potential of biodegradable surface-modified polymeric nanoparticles as clinically translatable, biomaterial-based vehicles for cancer gene therapy.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Kim J,Kang Y,Tzeng SY,Green JJdoi
10.1016/j.actbio.2016.05.040subject
Has Abstractpub_date
2016-09-01 00:00:00pages
293-301eissn
1742-7061issn
1878-7568pii
S1742-7061(16)30268-9journal_volume
41pub_type
杂志文章abstract::Multicomponent formulations coupled with complex processing conditions govern the final properties of photopolymerizable dental composites. In this study, a single test substrate was fabricated to support multiple formulations with a gradient in degree of conversion (DC), allowing the evaluation of multiple processing...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.01.043
更新日期:2009-07-01 00:00:00
abstract::The humid atmosphere and permanent occurrence of chewing forces in the oral environment lead to degradation of ceramics used for prosthetic restorations. The aim of this in vitro study was to evaluate the influence of artificial aging on the load-bearing capacity of four-unit bridges, with both undamaged and predamage...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.04.012
更新日期:2008-09-01 00:00:00
abstract::Antibiotic resistance of bacterial biofilms limits available treatment methods for implant-associated orthopaedic infections. This study evaluated the effects of applying cathodic voltage-controlled electrical stimulations (CVCES) of -1.5V and -1.8V (vs. Ag/AgCl) to coupons of commercially pure titanium (cpTi) incubat...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.11.056
更新日期:2017-01-15 00:00:00
abstract::Whales, dolphins, and porpoises have unusual vaginal folds of unknown function(s) that are hypothesized to play an important role in sexual selection. The potential function of vaginal folds was assessed by testing the mechanical properties of common bottlenose dolphin (Tursiops truncatus) reproductive tract tissues i...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.01.012
更新日期:2019-03-01 00:00:00
abstract::Peripheral arterial disease differentially affects the superficial femoral (SFA) and the popliteal (PA) arteries, but their morphometric, structural, mechanical, and physiologic differences are poorly understood. SFAs and PAs from 125 human subjects (age 13-92, average 52±17 years) were compared in terms of radii, wal...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.11.025
更新日期:2021-02-01 00:00:00
abstract::Cardiac fibrosis, an important pathological feature of structural remodeling, contributes to ventricular stiffness, diastolic dysfunction, arrhythmia and may even lead to sudden death. Matrix stiffness, one of the many mechanical factors acting on cells, is increasingly appreciated as an important mediator of myocardi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.01.031
更新日期:2014-06-01 00:00:00
abstract::Despite progress in use of decellularized lung scaffolds in ex vivo lung bioengineering schemes, including use of gels and other materials derived from the scaffolds, the detailed composition and functional role of extracellular matrix (ECM) proteoglycans (PGs) and their glycosaminoglycan (GAG) chains remaining in dec...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.11.029
更新日期:2020-01-15 00:00:00
abstract::We compared porous silicon (pSi) with smooth Si as chip-implant surfaces in a nerve regeneration setting. Silicon chips can be used for recording neural activity and are potential nerve interface devices. A silicon chip with one smooth and one porous side inserted into a tube was used to bridge a 5 mm defect in rat sc...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.02.010
更新日期:2009-07-01 00:00:00
abstract::In this research, the flexural performance of hedgehog spines is investigated in four ways. First, X-ray micro-computed tomography (μCT) is employed to analyze the complex internal architecture of hedgehog spines. μCT images reveal distinct structural morphology, characterized by longitudinal stringers and transverse ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.04.036
更新日期:2019-08-01 00:00:00
abstract::The use of human mesenchymal stromal cells (hMSC) for treating diseased tissues with poor vascularization has received significant attention, but low cell survival has hampered its translation to the clinic. Bioglasses and glass-ceramics have also been suggested as therapeutic agents for stimulating angiogenesis in so...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.12.009
更新日期:2018-02-01 00:00:00
abstract::In vitro degradation and chondrocyte-encapsulation of chitosan hydrogel made of crosslinkable and water-soluble chitosan derivative (CML) at neutral pH and body temperature were studied with respect to weight loss, cytoviability, DNA content and cell morphology. In vitro degradation of the chitosan hydrogels was sensi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2006.06.007
更新日期:2007-01-01 00:00:00
abstract::Surgical suture is a strand of biocompatible material designed for wound closure, and therefore can be a medical device potentially suitable for local drug delivery to treat pain at the surgical site. However, the preparation methods previously introduced for drug-delivery sutures adversely influenced the mechanical s...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.06.003
更新日期:2013-09-01 00:00:00
abstract::Antimicrobial peptides (AMPs) are currently receiving interest as an alternative to conventional antibiotics to treat biomaterial-associated infection. However, the inherent instability of such peptides often limits their efficacy in intended clinical applications. Covalent immobilization of AMPs to surfaces is one st...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.10.039
更新日期:2019-01-01 00:00:00
abstract::The aim of this work was to study the phase transformation during the setting reaction of two calcium phosphate bone cements based on either alpha tricalcium phosphate (alpha-TCP) or tetracalcium phosphate (TetCP) initial solid phase, and a magnesium carbonate-phosphoric acid solution as the hardening liquid. Low mole...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.01.006
更新日期:2008-07-01 00:00:00
abstract::Diabetics are prone to chronic wounds that have slower healing, and methods of accelerating the wound closure and to ensure protection from infections are critically needed. MicroRNA-146a gets dysregulated in diabetic wounds and injection of this microRNA combined with reactive oxygen species-scavenging cerium oxide n...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.11.014
更新日期:2020-01-01 00:00:00
abstract::Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Autophagy has been shown to facilitate sorafenib resistance. miR-375 has been shown to be an inhibitor of autophagy. In this study, miR-375 and sorafenib were co-loaded into calcium carbonate nanoparticles with lipid coating (miR-375/Sf-LCC NPs). The n...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.03.022
更新日期:2018-05-01 00:00:00
abstract::Analytical protocol greatly influences the measurement of human serum albumin (HSA) adsorption to commercial expanded polytetrafluororethylene (ePTFE) exhibiting superhydrophobic wetting properties. Degassing of buffer solutions and evacuation of ePTFE adsorbent to remove trapped air immediately prior to contact with ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.11.003
更新日期:2009-06-01 00:00:00
abstract::Calcium hydroxide (Ca(OH)(2)) has been broadly used in endodontics, including apexification to obtain apical closure by mineralization. However, the detailed mechanism of mineralization induced by Ca(OH)(2) is still unclear. This study focuses on the function of calcium and hydroxyl ions which dissociate from Ca(OH)(2...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.08.005
更新日期:2010-02-01 00:00:00
abstract::Abdominal aortic aneurysms (AAAs), a prototypic proteolytic cardiovascular disorder, are localized expansions of the aortal wall. Chronically upregulated and overexpressed proteases irreversibly degrade and disrupt the elastic matrix, which provides stretch and recoil properties to the aortal wall. Adult vascular smoo...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.05.037
更新日期:2020-08-01 00:00:00
abstract::Cell transplantation therapies to treat diseases related to dysfunction of retinal ganglion cells (RGCs) are limited in part by an inability to navigate to the optic nerve head within the retina. During development, RGCs are guided by a series of neurotrophic factors and guidance cues; however, these factors and their...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.08.032
更新日期:2014-12-01 00:00:00
abstract::Poloxamers, or pluronics, have been proposed as biomimetic substitutes for physiological gels. Concern regarding their ability to resist swelling under fluid flows has impeded their implementation. Using a combination of techniques including cryo-TEM and rapid X-ray imaging, we found that rapid flow rates stabilized t...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.07.021
更新日期:2019-09-15 00:00:00
abstract::Nano-sized objects such as liposomes are modified by adsorption of biomolecules in biological fluids. The resulting corona critically changes nanoparticle behavior at cellular level. A better control of corona composition could allow to modulate uptake by cells. Within this context, in this work, liposomes of differen...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.02.018
更新日期:2020-04-01 00:00:00
abstract::Two of the most prominent challenges that limit the clinical success of siRNA therapies are a lack of control over cargo release from the delivery vehicle and an incomplete understanding of the link between gene silencing dynamics and siRNA dosing. Herein, we address these challenges through the formulation of siRNA p...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.01.003
更新日期:2017-03-01 00:00:00
abstract::Throughout the process of aging, dynamic changes of bone material, micro- and macro-architecture result in a loss of strength and therefore in an increased likelihood of fragility fractures. To date, precise contributions of age-related changes in bone (re)modeling and (de)mineralization dynamics to this fragility inc...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.02.007
更新日期:2020-04-01 00:00:00
abstract:UNLABELLED:The present study serves three main functions. First, it presents a novel random copolymer, made of octadecyl acrylate hydrophobic blocks and 2-(dimethylamino)ethyl methacrylate hydrophilic groups, and it zwitterionic form. Second, random copolymer and zwitterionic random copolymer, OmDn and Z-OmDn, are used...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.01.031
更新日期:2016-08-01 00:00:00
abstract::Infection is a major cause of failure of inserted or implanted biomedical devices (biomaterials). During surgery, bacteria may adhere to the implant, initiating biofilm formation. Bacteria are also observed in and recultured from the tissue surrounding implants, and may even reside inside host cells. Whether these bac...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.08.012
更新日期:2014-12-01 00:00:00
abstract::Hydrogel microspheres with the capability to interact with charged species such as various drugs by ion-exchange processes are useful in a variety of biomedical applications. Such systems have been developed to allow active loading of the microsphere with chemotherapeutic agents in the hospital pharmacy for subsequent...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.02.013
更新日期:2017-04-15 00:00:00
abstract::The quest for predictive tumor markers for osteosarcoma (OS) has not well progressed over the last two decades due to a lack of preclinical models. The aim of this study was to investigate if microenvironmental modifications in an original humanized in vivo model alter the expression of OS tumor markers. Human bone mi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.02.051
更新日期:2019-04-15 00:00:00
abstract::High porosity and pore interconnectivity are important features of a successful tissue engineering scaffold. The objective of this work was to optimize the pore interconnectivity and to increase the porosity of an elastomeric degradable/polar/hydrophobic/ionic (D-PHI) polyurethane porous scaffold while maintaining its...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2010.06.018
更新日期:2010-11-01 00:00:00
abstract::Palliation therapy for dysphagia using esophageal stents is the current treatment of choice for those patients with inoperable esophageal malignancies. However, the metallic and plastic stents currently used in the clinical setting may cause complications, such as tumor ingrowth and stent migration into the stomach. T...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.10.035
更新日期:2019-01-01 00:00:00