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Radionuclide Labeling and Imaging of Magnetic Nanoparticles
Published in Nguyễn T. K. Thanh, Clinical Applications of Magnetic Nanoparticles, 2018
Benjamin P. Burke, Christopher Cawthorne, Stephen J. Archibald
Although such xenograft models allow the use of human tissue, a key disadvantage is the absence of adaptive immunity in the host, which is not reflective of the clinical situation. Syngeneic models include a functional host immune system, and commonly consist of murine cells that have spontaneously arisen or been induced, and are implanted into a genetically related host in an ectopic or orthotopic site. The 4T1 model (murine breast cancer cells implanted into the mammary fat pad of Balb/C mice) is often reported for NP evaluation, with fluorescent and luminescent cell variants reported for imaging of disease burden.130 Syngeneic models also include mice that have been genetically engineered to bear cell lineages that mimic the mutational sequence undergone by particular cancer types (genetically engineered mouse models, GEMMs). There is some evidence that these models better reflect the clinical situation.131
Quantum Dots Designed for Biomedical Applications
Published in Claudia Altavilla, Enrico Ciliberto, Inorganic Nanoparticles: Synthesis, Applications, and Perspectives, 2017
Ragusa Andrea, Zacheo Antonella, Aloisi Alessandra, Pellegrino Teresa
Papaggiannaros et al. utilized long-circulating NIR QD-PEGs incorporated into micelles (QD-Ms) for both tumor detection and for biodistribution studies (Papagiannaros et al. 2009). 4T1 murine breast cancer cells were injected subcutaneously in mice to produce tumor. After 2 weeks, QD-Ms or commercially QD-PEGs were injected into the tumor-bearing mice via the tail vein. Comparing the two treatments, the authors observed significant differences in their biodistribution patterns. Within 1 h after injection, QD-Ms accumulated rapidly in the organs and tumor resulting in high intensity of the signal while after the whole 6 h observation period, a limited fluorescence was observed. The QD-PEGs produced the maximum signal-to-noise ratio only after 3 h, with a diffuse fluorescence over the entire body of the animal and poorly contrasted images due to their longer time circulation in blood vessels (in tissues around tumor). These results clearly demonstrated that functionalized QD-Ms were deposited faster in organs and tumors and were also cleared faster than QD-PEGs.
Sustainable Green Polymeric Nanoconstructs for Active and Passive Cancer Therapeutics
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Ankit Rochani, Sreejith Raveendran, D. Sakthi Kumar
Heparin is water soluble with known pharmacological activity and biodegradable in nature. This makes it an interesting biomaterial for developing NPs for anticancer nanomedicine. Being anionic in nature, this material can be used for developing NPs by classical polyelectrolyte complexation method [148]. In order to improve its characteristics for drug delivery applications, this biomaterial is often complexed or grafted with natural or synthetic hydrophobic polymers. For example, poly (β-benzyl-L-aspartate) (PBCA), polycaprolactone (PCL) or deoxycholic acid (DOCA) has been used for the development of heparin-hybrid biomaterials for anticancer nanotherapy as shown in Fig. 7.8. Heparin-DOCA material was used for the development of nanoparticle (180 to 200 nm), which was used for the delivery of DOX. These NPs were assessed to have anticancer potential towards murine squamous cell carcinoma (SCC) and human umbilical vein endothelial cells (HUVEC) under in vitro conditions [149]. In another study, caspase-activated DOX/heparin composite NPs were developed. Here, DEVD-S-DOX (caspase-activated) prodrug was developed and it was co-encapsulated with DOX in heparin to form NPs of the size of around 123 nm. The study showed under in vivo condition that this nanomedicine can work considerably well for the caspase-3 activated treatment of murine squamous cell carcinoma [150]. The free carboxyl groups present in heparin molecules makes it an interesting biomaterial for the development of drug-heparin nanoconjugates by forming covalent interactions. For instance, pH-responsive, dendronized-heparin-DOX self-assembled NPs (as shown in Fig. 7.8) of size around 80 nm were developed. It was found to be effective against 4T1 breast cancer tumors [151]. This chemically conjugated nanoconstruct showed relatively smaller particle size compared to other self-assembled nanomedicine. Further, thiol-functionalized heparins were also developed for synthesis of heparin-AuNPs for photodynamic therapy [152]. These studies clearly indicated the importance of heparins for passive targeted therapies of cancer.
pH-sensitive curcumin conjugated micelles for tumor triggered drug delivery
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Hamid Rashidzadeh, Seyed Jamal Tabatabaei Rezaei, Sahar Zamani, Elnaz Sarijloo, Ali Ramazani
In this study, a novel drug vehicle based on glycidyl azide polymer (GAP) and monomethoxy polyethylene glycol (MPEG) were synthesized to improve water-solubility of the hydrophobic chemotherapeutic agents (CUR). Our method is based on the simple conjugation of CUR into copolymeric vehicles bearing amine pendent groups through imine linkage bonds, which is stable under normal physiological condition while could easily dissociate by a weak acidic environment and subsequently the pro-drug is then activated to inhibit cell growth. In vitro drug release revealed that this nano-conjugate is stable at normal physiological environment but susceptible to mild acidic conditions which resulted in pH-trigger CUR release. In addition, the PCCs exhibited excellent cytotoxicity potential against 4T1 mouse breast cancer cell line whereas the drug vehicle had no significant effects on cell viability of 4T1 cell line since the cell viability percentage was over 82% at high concentration of carrier. Also, the drug vehicles did not display considerable toxicity against A. salina even at high doses. In addition, the synthesized PDCs presented hemolysis below 6% which indicate the hemocompatibility of the synthesized drug vehicle. Moreover, oral acute toxicity (LD50) was another assay which confirmed the safety of synthesized drug vehicle, since all experimental animal which given the highest concentration of drug vehicle were alieved after one week. According to our results it can be concluded that these smart pH-sensitive PCCs may provide a promising approach for delivery of the anticancer drugs to cancer cells.
Stereocomplex micelle loaded with paclitaxel for enhanced therapy of breast cancer in an orthotopic mouse model
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Longyi Piao, Yongmeng Li, Hanwen Zhang, Jing Jiang
The cytotoxicities of free PTX and SCM/PTX were evaluated by MTT assay. In detail, 4T1 cells were seeded in 96-well plates (7 × 103 cells per well) in 200 μL of culture medium and incubated at 37 °C for 24 h. And then, the free PTX and SCM/PTX with a PTX concentration from 0.16 to 10.0 μg mL−1 in 20.0 μL of PBS were added to each well and cultured for another 48 h. After that, the cells were subjected to MTT assay. The absorbance of medium was measured on a Bio-Rad 680 microplate reader at 490 nm. The relative cell viability was calculated by comparing the absorbance at 490 nm with control wells containing only cell culture medium. Data were presented as means ± standard deviation (n = 6).
Fabrication of silk fibroin film enhanced by acid hydrolyzed silk fibroin nanowhiskers to improve bacterial inhibition and biocompatibility efficacy
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Minjie Lin, Wenjiao Xie, Xiuwen Cheng, Yuncong Yang, Jegatheeswaran Sonamuthu, Ying Zhou, Xiaogang Yang, Yurong Cai
To confirm the adding of SNWs is beneficial to the growth and adhesion of cells [29], the growth and adhesion of 4T1 cells on the SNWs/RSF film were evaluated. Firstly, the films were sterilized by UV and placed into the 12-well culture plate. Washing each sample three times with PBS before the cell seeding. Subsequently, 1 mL of 4T1 cells suspension with a cell density of 1 × 104 cells/cm2 was seeded in each well and cultured at 37 °C in 5% CO2 for 24 h, and observing the cell morphology under the inverted microscope (OLYMPUS, China).