scholarly journals Mechanism Study of Thermally Induced Anti-Tumor Drug Loading to Engineered Human Heavy-Chain Ferritin Nanocages Aided by Computational Analysis

Biosensors ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 444
Author(s):  
Shuang Yin ◽  
Yongdong Liu ◽  
Sheng Dai ◽  
Bingyang Zhang ◽  
Yiran Qu ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Heavy Chain ◽  
Computational Analysis ◽  
Drug Loading ◽  
Size Exclusion ◽  
In Vitro Tests ◽  
Mechanism Study ◽  
Thermally Induced ◽  
Recovery Yield ◽  
Loading Ratio

Diverse drug loading approaches for human heavy-chain ferritin (HFn), a promising drug nanocarrier, have been established. However, anti-tumor drug loading ratio and protein carrier recovery yield are bottlenecks for future clinical application. Mechanisms behind drug loading have not been elaborated. In this work, a thermally induced drug loading approach was introduced to load anti-tumor drug doxorubicin hydrochloride (DOX) into HFn, and 2 functionalized HFns, HFn-PAS-RGDK, and HFn-PAS. Optimal conditions were obtained through orthogonal tests. All 3 HFn-based proteins achieved high protein recovery yield and drug loading ratio. Size exclusion chromatography (SEC) and transmission electron microscopy (TEM) results showed the majority of DOX loaded protein (protein/DOX) remained its nanocage conformation. Computational analysis, molecular docking followed by molecular dynamic (MD) simulation, revealed mechanisms of DOX loading and formation of by-product by investigating non-covalent interactions between DOX with HFn subunit and possible binding modes of DOX and HFn after drug loading. In in vitro tests, DOX in protein/DOX entered tumor cell nucleus and inhibited tumor cell growth.

Tumor Cell Surface Display of Immunoglobulin Heavy Chain Fc by Gene Transfer as a Means to Mimic Antibody Therapy

2005 ◽  
Vol 0 (0) ◽  
pp. 050701034702008
Author(s):  
David S. Riddle ◽  
Laura Sanz ◽  
Heung Chong ◽  
Jill Thompson ◽  
Richard G. Vile
Keyword(s):  
Gene Transfer ◽  
Cell Surface ◽  
Tumor Cell ◽  
Heavy Chain ◽  
Surface Display ◽  
Antibody Therapy ◽  
Immunoglobulin Heavy Chain ◽  
Cell Surface Display

Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia

Blood ◽  
2000 ◽  
Vol 95 (8) ◽  
pp. 2651-2658 ◽  
Author(s):  
John W. Donovan ◽  
Marco Ladetto ◽  
Guangyong Zou ◽  
Donna Neuberg ◽  
Christina Poor ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tumor Cell ◽  
B Cell ◽  
Heavy Chain ◽  
Real Time Pcr ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
B Cell Malignancies ◽  
Normal Cells ◽  
Pcr Method

Tumor-related immunoglobulin heavy-chain (IgH) rearrangements are markers for polymerase chain reaction (PCR) detection of minimal residual disease (MRD) in B-cell malignancies. Nested PCR with patient IgH allele-specific oligonucleotide primers can detect 1 tumor cell in 104 to 106 normal cells. In childhood acute lymphoblastic leukemia (ALL), persistence of PCR-detectable disease is associated with increased risk of relapse. The clinical significance of qualitative PCR data can be limited, however, because patients can harbor detectable MRD for prolonged periods without relapse. Recent studies indicate that a quantitative rise in tumor burden identifies patients who are at high risk for relapse. Therefore, an efficient and reliable PCR method for MRD quantification is needed for ALL patients. We have developed a real-time PCR method to quantify MRD with IgH VH gene family consensus fluorogenically labeled probes. With this method, a small number of probes can be used to quantify MRD in a large number of different patients. The assay was found to be both accurate and reproducible over a wide range and capable of detecting approximately 1 tumor cell in 5 × 104 normal cells. We demonstrate that this methodology can discriminate between patients with persistence of MRD who relapse and those who do not. This technique is generally applicable to B-cell malignancies and is currently being used to quantify MRD in a number of prospective clinical studies at our institution.

Anti-Tumor Study of H6, a 4-Substituted Coumarins Derivative, Loaded Biodegradable Self-Assembly Nano-Micelles In Vitro and In Vivo

2019 ◽  
Vol 15 (7) ◽  
pp. 1515-1531 ◽  
Author(s):  
Zejiang Zhu ◽  
Zhengying Su ◽  
Jianhong Yang ◽  
Huili Liu ◽  
Minghai Tang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Therapeutic Window ◽  
Tumor Growth Inhibition ◽  
Mechanism Study ◽  
Tumor Models ◽  
Substituted Coumarins

In our previous study, we identified a class of 4-substituted coumarins as a powerful microtubule inhibitors binding to the colchicine site of β-tubulin. H6 showed potent anti-proliferative ability with IC50 values from 7 to 47 nM, and remarkable ability to reduce tumor growth in several xenograft models including taxol resistant tumor models. However, the extremely hydrophobicity limited its clinical application. In this study, to improve the anticancer activity and reduce the toxicity of H6, we successfully prepared MPEG-PCL with different proportions and H6-loaded polymeric micelles (H6/MPEG2kPCL2k micelles) by a simple thin-film hydration method. The prepared H6/MPEG-PCL micelles had a drug loading of 3.79 ± 0.001%, an encapsulation efficiency of 98.00 ± 0.41%, a mean particle size of 30.45 ± 0.18nm and a polydispersity index (PDI) of 0.096 ± 0.009. Computer simulation results revealed a good compatibility of H6 and MPEG2k-PCL2k copolymer. In in vitro release study and pharmacokinetic study showed H6 micelles can release H6 over an extended period. Furthermore, H6 micelles possessed comparative effect as free H6 in inhibiting cell growth, preventing cell migration, and inducing apoptosis. Mechanism study identified that H6 is a novel reversible microtubule inhibitor. In in vivo studies, H6 micelles exhibited tumor growth inhibition on two pulmonary metastatic tumor models (B16/F10 and 4T1). Importantly, H6 micelles significantly improved the solubility, reduced the toxicity, extended the half-life of drugs, and augmented the therapeutic window. All these results imply that H6 micelles have great potential for suppression of tumor metastasis.

Application of composite dissolving microneedles with high drug loading ratio for rapid local anesthesia

2018 ◽  
Vol 121 ◽  
pp. 330-337 ◽  
Author(s):  
Haohui Zhan ◽  
Fengsen Ma ◽  
Yingcong Huang ◽  
Jie Zhang ◽  
Xiayun Jiang ◽  
...  
Keyword(s):  
Local Anesthesia ◽  
Drug Loading ◽  
High Drug ◽  
Dissolving Microneedles ◽  
Loading Ratio ◽  
High Drug Loading

scholarly journals Cordycepin Induced MA-10 Mouse Leydig Tumor Cell Apoptosis through Caspase-9 Pathway

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Chun-Yi Jen ◽  
Chun-Yu Lin ◽  
Bu-Miin Huang ◽  
Sew-Fen Leu
Keyword(s):  
Tumor Cell ◽  
Cell Apoptosis ◽  
Tumor Cell Line ◽  
Phase Cell ◽  
Mechanism Study ◽  
Caspase 9 ◽  
M Phase ◽  
Apoptotic Effect ◽  
Leydig Tumor Cells ◽  
Induced Apoptosis

In the present study, the apoptotic effect of cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by cordycepin (10 μM to 5 mM for 24 h), and cells with plasma membrane blebbing could be observed by 100 μM cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 μM to 5 mM) and duration (3–24 h) of cordycepin treatment increased (P< 0.05). Cordycepin at 100 μM and 1 mM for 24 h treatment induced significant DNA fragmentation (P< 0.05). In addition, the percentage of G1 and G2/M phase cell significantly declined by cordycepin (100 μM and 1 mM) for 24 h treatment, while the percentages of subG1 phase cell increased by 100 μM and/or 1 mM cordycepin in 6, 12 and 24 h treatments (P< 0.05), respectively, which highly suggested that cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH2terminal kinase (JNK) or reactive oxygen species (ROS) inhibitors plus cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.

Sterically stabilized polyionic complex nanogels of chitosan lysate and PEG-b-polyglutamic acid copolymer for delivery of irinotecan active metabolite (SN-38)

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohsen Salmanpour ◽  
Mahvand Saeed-Vaghefi ◽  
Samira Sadat Abolmaali ◽  
Alimohamad Tamaddon
Keyword(s):  
Glutamic Acid ◽  
Active Metabolite ◽  
Drug Loading ◽  
Free Particle ◽  
Hydrolytic Degradation ◽  
Weight Ratio ◽  
Size Exclusion ◽  
Spherical Particles ◽  
Wide Range ◽  
Polyionic Complex

Background:: Polyionic Complex (PIC) nanogels are promising delivery systems with numerous attractions such as simple, fast, and organic solvent-free particle formation and mild drug loading conditions. Among polyelectrolytes, poly (L-amino acid) copolymers such as poly (ethylene glycol)-block-poly (L-glutamic acid) copolymers (PEG-b-PGlu) are interesting biocompatible and biodegradable candidates bearing carboxylic acid functional groups. Objectives:: Aiming to solubilize and to preserve short-acting irinotecan active metabolite (SN38), sterically stabilized PIC nanogels were prepared through electrostatic charge neutralization between PEG-b-PGlu and chitosan lysate, a polycationic natural polymer obtained through digestion of chitosan by hydrogen peroxide oxidation and is soluble in a wide range of pH. Methods:: Synthesis of PEG-b-PGlu was accomplished by N-carboxyanhydride polymerization of γ -benzyl L-glutamic acid, which is initiated by methoxy PEG-NH2 and successive debenzylation reaction. Result:: The resulting block copolymer was characterized by FTIR, 1H-NMR, and Size Exclusion Chromatography (SEC). Self-assembling properties of the PIC nanogels were investigated by pyrene assay, Dynamic Light Scattering (DLS), and Transmission Electron Microscopy (TEM), indicating formation of homogeneous spherical particles with a mean size of 28 nm at the PEG-b-PGlu concentrations/LMWC weight ratio of 5:1. Upon direct loading of SN38, the drug solubility enhanced more than 4×103 folds with a mean loading efficiency of 89% and the drug loading of 30%. PIC nanogels exhibited zeta potential of +1 mV, acceptable biocompatibility, and superior cytotoxicity in murine colorectal carcinoma (CT26 cell line) compared to free drug. Conclusion:: In addition, the PIC nanogels provided SN38 protection against hydrolytic degradation in physiologic condition. Conclusively, the well-tuned PIC nanogels are suggested as a potential biocompatible nanocarrier for SN38 delivery.

FABRICATION AND IN VITRO EVALUATION OF FOLATE-MODIFIED IRON FERRITE NANOPARTICLES WITH HIGH DOXORUBICIN LOADING FOR RECEPTORS-MAGNETIC-GUIDED DRUG DELIVERY

NANO ◽  
2014 ◽  
Vol 09 (02) ◽  
pp. 1450021 ◽  
Author(s):  
LIN GUO ◽  
WENCE DING ◽  
FANDIAN MENG
Keyword(s):  
Tumor Cells ◽  
Drug Loading ◽  
Ferrite Nanoparticles ◽  
Reactant Ratio ◽  
Folate Receptors ◽  
Dual Functional ◽  
Dual Targeting ◽  
Loading Ratio ◽  
Iron Ferrite

Folate-modified iron ferrite nanoparticles with high doxorubicin loading (FDMP) were developed for dual targeting of tumor cells. Large quantities of doxorubicin and folate ligand were chemically coupled to the synthesized dual-functional magnetic nanoparticles by using the multihand cross-linker poly-L-glutamic acid. FDMP exhibits high drug loading ability, narrow size distribution and pH sensitivity to drug release. The drug loading ratio and the magnetic response can be adjusted by controlling the reactant ratio. FDMP possesses high magnetic-guided ability and exhibits enhanced uptake by folate receptors expressing tumor cells and increased cancer cell cytotoxicity.

Antheraea pernyi Silk Fibroin Nanoparticles for Drug Delivery

2014 ◽  
Vol 27 ◽  
pp. 75-81 ◽  
Author(s):  
Shen Zhou Lu ◽  
Juan Wang ◽  
Li Mao ◽  
Gui Jun Li ◽  
Jian Jin
Keyword(s):  
Drug Delivery ◽  
Silk Fibroin ◽  
Molecular Conformation ◽  
Ph Value ◽  
Drug Loading ◽  
Antheraea Pernyi ◽  
Silk Fibroin Nanoparticles ◽  
Loading Ratio ◽  
Α Helix ◽  
Average Size

Silk nanoparticles were easily obtained from regenerated Antheraea Pernyi Silk Fibroin (ASF). The morphology and average size of the silk particles was sensitive to pH value of fibroin solution. The diameter of nanoparticles prepared was in the range of 30 nm to 1000 nm with a narrow size distribution. On this process, the molecular conformation of regenerated ASF changed from α-helix to β-sheet structure. The shape of prepared nanoparticles were regular spherical structure when the pH value was about 4.3 (pI) in ASF solution. Doxorubicin hydrochloride (DOX) was loaded in the ASF particles as drug release model and the drug-loading ratio was 3.4 %. The release rate of DOX from ASF nanoparticles was pH sensitive. After 23 days release, there was still 84% DOX in the ASF nanoparticles. The result suggested that the ASF nanoparticles might be suitable microcarriers for drug delivery.

Sign in / Sign up

Export Citation Format

Share Document