Hyperbranched amphiphilic polymer with folate mediated targeting property
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Folate receptor
Lactide
Targeted delivery is a highly desirable strategy for diagnostic imaging due to enhanced efficacy and reduced dosage/toxicity. The need to develop target-specific magnetic resonance imaging (MRI) contrast agents to aid in disease characterization is highly essential. In this study, a specific contrast agent, Gd-DTPA-poly-L-lysine (PL-Gd-DTPA)-folate, was synthesized and evaluated for its efficacy as a targeted agent for the imaging of tumors that overexpress the folate receptor. Folic acid was conjugated to PL-Gd-DTPA via the ε-amino groups. The receptor binding properties of folate-PL-Gd-DTPA were studied in cultured tumor cells that overexpressed the folate receptor. The tumor-selecting properties of folate-PL-Gd-DTPA were then evaluated in BALB/c mice bearing subcutaneously implanted folate receptor-positive tumors. Tissue MR signal intensities were measured at six different time-points. In the in vitro study, the folate-PL-Gd-DTPA was able to bind to these cells, which overexpressed the folate receptor, as with free folic acid. Excellent tumor selectivity was also shown in the animal model; after the success of injection of folate-PL-Gd-DTPA, a maximum intensity increase of 125.4% was observed from pre-injection compared to post-injection images of the tumor at the 48 h time-point. The liver enhancement was non-specific and the muscle signal intensity at any time-point after injection showed no statistical difference with that observed before injection. Folate-PL-Gd-DTPA is a promising, novel receptor-specific MRI contrast agent with potential applications in the imaging of human folate receptor-positive tumors.
Folate receptor
MRI contrast agent
Pentetic acid
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Macrocyclic amphiphiles, a type of amphiphiles synthesized based on macrocyclic compounds, have attracted much attention over the past decades due to their unique superiority in the construction of various functional nanomaterials. The regulation of the state of macrocyclic amphiphiles by introducing stimuli-responsive motif to macrocyclic amphiphiles is an efficient way to extend their applications in diverse fields. Herein, pillararene-based macrocyclic amphiphile H1 was prepared. H1 can act as single-chain amphiphile to self-assemble into micelles in water when the pH was ≥5.0. H1 can be protonated to turn into H2 when pH changed to <5.0. Interestingly, H2 formed [c2]daisy chain-based bola-type supramolecular amphiphile. This bola-type supramolecular amphiphile self-assembled into nanosheets in water. Therefore, pH-induced transition between single-chain macrocyclic amphiphile and bola-type amphiphile and the corresponding self-assembly system based on pillararene in water were constructed.
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Radius of gyration
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Polylysine
Antibacterial peptide
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This chapter contains sections titled: Introduction General Principles of DLS (Photon Correlation Spectroscopy) Particle Size Standards Applied to DLS Unique DLS Instruments Sample Characterization Using DLS Measurements of Nanoparticles Result of DLS Characterization Conclusion References
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Objective To study folate-conjugated Gd-DTPA-Poly-L-Lysine (folate-PL-Gd-DTPA) as MR targeting agent to tumor cells via folate receptor, to evaluate feasibility and effectiveness by observing MR signal variations and imaging feature of pulmonary tumor xenografts in nude mice using this contrast material. Methods (1) Using Poly-L-Lysine (PL) as linker, after PL was tethered with caDTPA, GdCl_3 was added to label DTPA- PL, then PL-Gd-DTPA was conjugated to folate, a specific MR contrast agent, was thus prepared. (2) Using high performance liquid chromatography (HPLC) to evaluate the conjugate purity, and the ICP-AES to test Gd~(3+) concentration, while the activity evaluated by competitive folate receptor binding with folic acid. (3) Folate-PL-Gd-DTPA as specific contrast agents (study group, n = 6) and Gd-DTPA as non-specific contrast agents (control group, n =4 ) was injected respectively into caudal vein of the nude mice which was pulmonary tumor xenografts as experimental model in the study. MRI was performed with plain scans, enhanced scans at 30 minutes,3 hours ,6 hours, 14 hours,24 hours,38 bouts,48 hours,62 hours and 72 hours after the success of injection. Signal intensities of tumors and muscles were measured. Results ( 1 ) folate-PL-Gd-DTPA was successfully synthesized with high affinity to folate receptor and high concentration of Gd~(3+) (56 Gd~(3+)/folate). (2) folate-PL-Gd-DTPA had an excellent tumor selectivity in pulmonary tumor xenografts in the animal model. After injection, the tumor signal intensity in the study group was significantly higher than that observed before injection; An average intensity increase of 125.4% was observed from pre-contrast to post-contrast images of the tumor, which was observed at 24-48 hours after injection; The muscle signal intensity at any time-point after injection showed no statistically difference with that observed before injection. In control group, the tumor signal intensity showed statistically difference with that observed before injection at 0. 5 hour and 3 hours, the biggest difference appeared at 0. 5 hour; The muscle signal intensity at 0. 5 hour time-point showed statistically difference with that observed before injection. Conclusion Folate- PL-Gd-DTPA could be combined to tumor ceils appetencially via folate receptor and significantly targeted to tumor cells with rich folate receptors for MR imaging.
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