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Surface Engineered Graphene Oxide and Its Derivatives
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Zaira Zaman Chowdhury, Abu Nasser Faisal, Shahjalal Mohammad Shibly, Devarajan Thangadurai, Saher Islam, Jeyabalan Sangeetha
As previously stated, chitosan (CS) was used as a vector for gene transfer and as a transporter for drugs. GO treated with CS has the potential to reduce its cytotoxicity while increasing its biocompatibility and capacity to carry the genes. Hepatic binder protein (HBP) is a type of glycoprotein receptor (ASGP/R) found over the hepatocytic membrane that recognizes galactose groups inside the de-sialylated glycoproteins. Thus, GO functionalized with lacto-sylated CS oligo-saccharide containing quaternary ammonium units may be used to improve the delivery of DNA inside the hepato-carcinoma (QGY-7703) cell matrix of humans (Cao et al. 2015). Additionally, using 1-pyrene-methylamine hydrochloride, GO may be grafted with folic acid (FA) to form a GO-PEG-FA/PyNH2 combination for cancer therapy and intracellular release of sRNA. PEG was utilized to enhance the solubility of this gene vector in serum and physiological media. The paradigm of multi-functionalization strategy, provided GO/PEI–PEG–FA/si-Stat-3 based system in order to achieve increased si-Stat-3 translation efficacy and subsequently decreased the toxicity. The results indicated that increasing the PEI weight ratios ramped up the transfection aptitude. Additionally, folate targeting facilitated the introduction of si-Stat-3 into SMMC-7721 cells with intent to lower the protein levels (Wang et al. 2016).
Polymeric Nanoparticles for Tumor-Targeted Drug Delivery
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Tania Betancourt, Amber Doiron, Lisa Brannon-Peppas
A possible limitation of folate targeting is the noted variability of FR expression levels not only between patients, but also within a single tumor.44 In addition, it has been reported that expression of FR in cancerous cell lines is not representative of those one sees in vivo.44 Consequently, screening protocols for FR expression will need to be utilized clinically in order to determine if folate-targeted therapies are appropriate.
Actively targeted nanocarriers for drug delivery to cancer cells
Published in Expert Opinion on Drug Delivery, 2019
Stefania Biffi, Rebecca Voltan, Barbara Bortot, Giorgio Zauli, Paola Secchiero
In humans, there are four isoforms of the FR (FRα, FRβ, FRγ, FRδ) [84]. Notwithstanding FRβ‘s expression on some cancers and on tumor-associated macrophages of many cancers, the Frα isoform has the most potential for active targeting strategies. Normal tissue distribution of FRα is relatively restricted to a limited number of polarized epithelia (uterus, placenta, choroid plexus, lung, and kidney), which expression localized only at the apical surface of polarized cells, preventing exposure to the circulation [84] (Figure 2). In the malignant context, intercellular junctions are lost and FRα loses its polarized cellular location, thus becoming positioned on the entire tumor cell surface (Figure 2). Due to the important role that FRα plays in cancer development and progression, this receptor is frequently highly overexpressed in several epithelial tumors, including a variable percentage of ovarian, breast, lung, kidney, and colon carcinomas [85]. This consequently enables the use of folate-targeting ligands to guide the receptor-mediated endocytosis of folate-targeted nanocarrier containing therapeutic payloads. Upon endocytosis, nanocarrier can release its content into the cytosol of the tumor cells. Indeed, several studies have been conducting to develop various conjugates that employ a folate ligand for active targeting [86] (Table 3).
Targeting efficiency of nanoliposomes on atherosclerotic foam cells: polyethylene glycol-to-ligand ratio effects
Published in Expert Opinion on Drug Delivery, 2020
Anastasia Darwitan, Yang Fei Tan, Yee Shan Wong, Anu Maashaa Nedumaran, Bertrand Czarny, Subbu Venkatraman
Finally, the effect of PEG-to-ligand ratio on cell uptake was evaluated (Figure 4). Serum-preincubated nanoliposomes containing PEG 2000-Folate (0.5 mol%) and varying ligand-free PEG lengths and concentrations were treated to foam cells. Our findings demonstrated that, firstly, the active targeting effect is present with PEG 750 (0.25–1 mol%) and PEG 2000 (0.25 mol%) liposomal formulations even in the presence of 80% serum. Secondly, the highest targeting efficiency was achieved at low PEG density with the configuration of longer folate spacer length and shorter folate-free PEG. This finding on the optimum configuration agrees with the previous reports using folate-liposomes and KB cells [28,29]. Our findings agree with our hypothesis that the targeting effect of folate-targeting nanoliposomes will progressively decrease and eventually be lost as PEG-to-ligand ratio is increased. We found that the value of PEG-to-ligand ratio at which the targeting effect is lost, is dependent on the PEG length (>2 for PEG 750; >0.5 for PEG 2000; <0.5 for PEG 5000). The same trend was observed in a study with nanoemulsion containing integrin specific arginine-glycine-aspartic acid (RGD) peptide and PEG 2000 on HUVEC cells [31] where a loss in targeting efficiency was observed at PEG/ligand ratio >3. The higher PEG/ligand ratio threshold could be due to the difference in the control, where peptide-free PEGylated nanoemulsions were used as the control in the report. Using the model by de Gennes et al. [32], we calculated that the PEG was predominantly in mushroom configuration, except for PEG 5000 from 3 mol% onwards were in brush configuration. Clearly, the brush configuration did not present any cell uptake enhancement. Typically, liposome morphology is adversely affected above 7 mol% (forming micelles instead of vesicles) [33], and thus we did not try higher PEG concentration.
Folate conjugation improved uptake and targeting of porous hydroxyapatite nanoparticles containing epirubicin to cancer cells
Published in Pharmaceutical Development and Technology, 2020
Legha Ansari, Mansooreh Derakhshi, Elnaz Bagheri, Nasser Shahtahmassebi, Bizhan Malaekeh-Nikouei
To evaluate the cytotoxicity effect of different types of HAp formulations, we incubated different formulations with C-26 cells. According to the MTT assay, free EPI, PEG-HAp-EPI, and FA-PEG-HAp-EPI exhibited IC50 values of 0.6016, 1.050, and 0.1558 mg/ml, respectively. This result indicates the intense effect of folate targeting on the uptake of folate functionalized nanoparticles by cells, as this type of nanoparticles showed a lower amount of IC50. The cytotoxicity of blank HAp was also investigated by MTT assay. The cell viability after 48 h incubation with HAp in maximum concentration was about 109%, which proves that HAp nanoparticles are biocompatible. This result is in agreement with the reported results of other studies (Bral and Mommaerts 2016). As shown in Figure 5, FA-PEG-HAp-EPI exhibited better cytotoxicity against the C-26 cancer cells than free EPI after 48 h. Nearly, the cell viability after 48 h incubation with FA-PEG-HAp-EPI is significantly lower than free EPI in all concentrations. The cell viability at the end of 48 h incubation with FA-PEG-HAp-EPI reaches 19% which is nearly two-fold better than that of treated with free EPI. The cell viabilities after incubation with concentrations of more than 0.03 mg/ml FA-PEG-HAp-EPI were significantly lower than PEG-HAp-EPI. The latter may attribute to more targeted folate functionalized nanoparticles being uptake by cancer cells compared to the uptake of similar non-targeted pegylated nanoparticles. In addition, the aforementioned drug release study showed that the released drug in acidic pH (e.g. endosome) in FA-PEG-HAp-EPI is more than PEG-HAp-EPI. So, it can concluded that the synergistic effect of a more released drug in acidic pH and targeting property of FA-PEG-HAp-EPI, lead to the lower viability in cells treated with FA-PEG-HAp-EPI compared to PEG-HAp-EPI. Our finding is in agreement with the results of the quantitative study reported by Sandoval et al. (Sandoval et al. 2015). The increase in cell uptake with folate ligand indicates that FA-PEG-HAp-EPI is a good candidate for use in targeting applications for destroying cancer cells as well as reduction of side effects.