Abstract:
:Combretastatin A4 (CA4) is a leading agent in vascular disrupting strategies for tumor therapy. Although many small-molecule prodrugs of CA4 have been developed to improve its solubility, the overall therapeutic efficiency is moderate. A key reason for this is the reversible effect that CA4 has on tubulin as well as its rapid clearance from plasma and tissues. In this study, we proposed a poly(l-glutamic acid)-CA4 conjugate (PLG-CA4) nanomedicine to fulfill the requirements for fully liberating the potential of CA4 on tumor therapy. Enhanced accumulation and retention of CA4 in tumor tissue, especially, high distribution and gradual release around tumor blood vessels resulted in prolonged vascular disruption and markedly enhanced therapeutic efficiency. We examined and compared the therapeutic effect of PLG-CA4 and commercial combretastatin-A4 phosphate (CA4P) in a murine colon C26 tumor. PLG-CA4 showed significantly prolonged retention in plasma and tumor tissue. Most importantly, the PLG-CA4 was mainly distributed around the tumor vessels because of its low tissue penetration in solid tumor. Pathology tests showed that PLG-CA4 treatment resulted in persistent vascular disruption and tumor damage 72h after a single injection, this in contrast to CA4P treatment, which showed quick relapse at an equal dose. Tumor suppression tests showed that PLG-CA4 treatment resulted in a tumor suppression rate of 74%, which indicates a significant advantage when compared to tumor suppression rate of the CA4P group, which was 24%. This is the first time that an advantage of the polymeric CA4 nanomedicine with low tissue penetration for solid tumor therapy has been shown. Thus, the results presented in this study provide a new idea for enhancing the tumor therapeutic effect of vascular disrupting agents. STATEMENT OF SIGNIFICANCE:Nanomedicine usually has low tissue penetration in solid tumors, which limits the efficacy of nanomedicine in most cases. But herein, we demonstrate a nanosized vascular disruptive agent (VDA) PLG-CA4 has supper advantages over small molecular combretastatin-A4 phosphate (CA4P) because the PLG-CA4 was mainly distributed around the tumor vessels due to its low tissue penetration in solid tumor.
journal_name
Acta Biomaterjournal_title
Acta biomaterialiaauthors
Liu T,Zhang D,Song W,Tang Z,Zhu J,Ma Z,Wang X,Chen X,Tong Tdoi
10.1016/j.actbio.2017.02.001subject
Has Abstractpub_date
2017-04-15 00:00:00pages
179-189eissn
1742-7061issn
1878-7568pii
S1742-7061(17)30096-Xjournal_volume
53pub_type
杂志文章abstract::Well-organized composite formations such as hierarchical nested-network (NN) structure in bone tissue and reticular connective tissue present remarkable mechanical strength and play a crucial role in achieving physical and biological functions for living organisms. Inspired by these delicate microstructures in nature,...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.02.003
更新日期:2018-04-01 00:00:00
abstract::Avidin was covalently conjugated to the surface of calcium phosphate nanoparticles, coated with a thin silica shell and terminated by sulfhydryl groups (diameter of the solid core about 50nm), with a bifunctional crosslinker connecting the amino groups of avidin to the sulfhydryl group on the nanoparticle surface. Thi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.05.049
更新日期:2017-07-15 00:00:00
abstract:UNLABELLED:The novel concept of modifying and enhancing the properties of existing functional micelles through self-complementary interactions has significant potential. In this study, a practical approach to living polymerization of functionalized thermoresponsive monomers enabled the incorporation of self-constituted...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.01.018
更新日期:2016-03-01 00:00:00
abstract::Bone replacement using synthetic and degradable materials is desirable in various clinical conditions. Most applied commercial materials are based on hydroxyapatite, which is not chemically degradable under physiological conditions. Here we report the effect of a long-term intramuscular implantation regime on the diss...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2011.05.022
更新日期:2011-09-01 00:00:00
abstract::To search for potential non-viral nucleic acids carriers, a series of novel cationic polymers, multi-armed poly(aspartate-graft-oligoethylenimine) (MP-g-OEI) copolymers were designed and synthesized by grafting different types of oligoethylenimine (OEI) to a multi-armed poly(l-aspartic acid) backbone. The as-synthesiz...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.02.007
更新日期:2013-06-01 00:00:00
abstract::Silicon-doped hydroxyapatite has been functionalized with biotin molecules as a new methodology for the attachment of proteins, peptides or growth factors through the formation of avidin-biotin complex in this material. Bioceramic biotinylation has been performed by esterification reaction between the OH groups of hyd...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.09.004
更新日期:2010-03-01 00:00:00
abstract::The antimicrobial properties of silver and copper nanoparticles were investigated using Escherichia coli (four strains), Bacillus subtilis and Staphylococcus aureus (three strains). The average sizes of the silver and copper nanoparticles were 3 nm and 9 nm, respectively, as determined through transmission electron mi...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2007.11.006
更新日期:2008-05-01 00:00:00
abstract::Tissue-derived extracellular matrix (ECM) biomaterials to regenerate the meniscus have gained increasing attention in treating meniscus injuries and diseases, particularly for aged persons and athletes. However, ECM scaffold has poor cell infiltration and can only be implanted using surgical procedures. To overcome th...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2015.01.027
更新日期:2015-04-01 00:00:00
abstract::Surface modification of poly(dl-lactic acid) (PLA) scaffolds has been performed using a biofunctional small peptide composed of collagen-like repetitive sequence and laminin-derived sequence (AG73-G(3)-(PPG)(5)) via hydrophobic interaction. The results of surface analysis suggest that AG73-G(3)-(PPG)(5) can be stably ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2009.12.001
更新日期:2010-06-01 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::Tissue-engineered temporomandibular joint (TMJ) discs offer a viable treatment option for patients with severe joint internal derangement. To date, only a handful of TMJ tissue engineering studies have been carried out and all have incorporated the use of synthetic scaffold materials. These current scaffolds have show...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2008.01.016
更新日期:2008-07-01 00:00:00
abstract::Antimicrobial peptides (AMPs), which are produced by multicellular organisms as a defense mechanism against competing pathogenic microbes, appear to be excellent candidates for the development of novel antimicrobial agents. Amphipathicity is traditionally believed to be crucial to the de novo design or systematic opti...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.08.043
更新日期:2014-01-01 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::Abnormal wound healing caused by the over-expression of collagen and fibronectin leads to fibrosis, the major complication of all treatment modalities. A three-layer nanofiber scaffold was designed, optimized, and fabricated. This scaffold comprised two supportive polycaprolactone (PCL)-chitosan layers on the sides an...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.06.031
更新日期:2020-09-01 00:00:00
abstract::Recent biotechnological progress has enabled the production of spider silk proteins, spidroins, in heterologous hosts. Matrices based on recombinant spidroins support stem cell growth and are well tolerated when implanted in living tissue, thus the material is highly attractive for use in regenerative medicine. Howeve...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2013.09.030
更新日期:2014-04-01 00:00:00
abstract::We report injectable nanoengineered hemostats for enhanced wound healing and tissue regeneration. The nanoengineered system consists of the natural polysaccharide, κ-carrageenan (κCA), loaded with synthetic two-dimensional (2D) nanosilicates. Nanoengineered hydrogels showed shear-thinning characteristics and can be in...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2018.01.045
更新日期:2018-04-01 00:00:00
abstract::Biomaterials made of biodegradable poly(α-hydroxyesters) such as poly(lactide-co-glycolide) (PLGA) are known to decrease the pH in the vicinity of the implants. Bioactive glass (BG) is being investigated as a counteracting agent buffering the acidic degradation products. However, in dentistry the question arises wheth...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2013.06.030
更新日期:2013-11-01 00:00:00
abstract::There is an increasing clinical need to design novel dental materials that combine regenerative and antibacterial properties. In this work the characterization of a recently developed sol-gel-derived bioactive glass ceramic containing silver ions (Ag-BG) is presented. The microstructural characteristics, ion release p...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.04.030
更新日期:2014-08-01 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::The innate biological response to peripheral nerve injury involves a complex interplay of multiple molecular cues to guide neurites across the injury gap. Many current strategies to stimulate regeneration take inspiration from this biological response. However, little is known about the balance of cell-matrix and Schw...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.10.008
更新日期:2015-01-01 00:00:00
abstract::Periodontal diseases like periodontitis and peri-implantitis have been linked with Gram-negative anaerobes. The incorporation of various chemotherapeutic agents, including metal ions, into several materials and devices has been extensively studied against periodontal bacteria, and materials doped with metal ions have ...
journal_title:Acta biomaterialia
pub_type: 杂志文章,评审
doi:10.1016/j.actbio.2014.03.028
更新日期:2014-08-01 00:00:00
abstract::Sr and CO3 co-substituted hydroxyapatite (SrCHA) nanopowder was synthesized by neutralization. The powder was characterized. The improved solubility in Hanks' balanced solution of SrCHA granules (400-600 microm of dimensional range), potentially usable as bone filler, was assessed and compared with that of an analogou...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2007.10.010
更新日期:2008-05-01 00:00:00
abstract::Titanium (Ti) based tissue engineering scaffolds can be used to repair damaged bone. However, successful orthopedic applications of these scaffolds rely on their ability to mimic the mechanical properties of trabecular bone. Selective laser melting (SLM) was used to manufacture scaffolds of a new β-Ti35Zr28Nb alloy fo...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2019.01.051
更新日期:2019-03-15 00:00:00
abstract::The present study focuses on apatite coating on collagen films, with various different densities of carboxyl groups, using an alternate soaking process. Anionic collagen (AC), which has different densities of carboxylic groups compared to native collagen (NC), was obtained by hydrolysis of carboxyamides of asparagine ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2007.02.008
更新日期:2007-09-01 00:00:00
abstract::The encapsulation of cells in microscale hydrogels can provide a mimic of a three-dimensional (3D) microenvironment to support cell viability and functions and to protect cells from the environmental stress, which have been widely used in tissue regeneration and cell therapies. Here, a microfluidics-based approach is ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2020.05.024
更新日期:2020-07-15 00:00:00
abstract::Full-length versions of the four main components of silk cocoons of Vespa simillima hornets, Vssilk1-4, were produced as recombinant proteins in Escherichia coli. In shake flasks, the recombinant Vssilk proteins yielded 160-330mg recombinant proteinl(-1). Films generated from solutions of single Vssilk proteins had a ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2014.05.013
更新日期:2014-08-01 00:00:00
abstract::Three protease-resistant bioorganic 304 stainless steel surfaces were created through the reaction of synthetic peptides consisting of the D-enantiomeric isomer (D-K122-4), the retro-inverso D-enantiomeric isomer (RI-K122-4), and a combination of the two peptides (D+RI) of the Pseudomonas aeruginosa PilA receptor bind...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2012.11.026
更新日期:2013-04-01 00:00:00
abstract::The mechanical properties of Bombyx mori silk fibroin (SF), such as elasticity and tensile strength, change remarkably upon hydration. However, the microscopic interaction with water is not currently well understood on a molecular level. In this work, the dynamics of water molecules interacting with SF was studied by ...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2016.12.052
更新日期:2017-03-01 00:00:00
abstract::This study investigated whether a novel alkali-based surface modification enhances in vitro mineralization as well as in vivo bone formation around titanium (Ti) implants in a femoral condyle model of 36 male Wister rats. All implant surfaces were grit-blasted and then received either acid-etching treatment, alkali-ba...
journal_title:Acta biomaterialia
pub_type: 杂志文章
doi:10.1016/j.actbio.2017.05.016
更新日期:2017-07-15 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