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RNA Nanotechnology and Extracellular Vesicles (EVs) for Gene Therapy
Published in Peixuan Guo, Kirill A. Afonin, RNA Nanotechnology and Therapeutics, 2022
Zhefeng Li, Fengmei Pi, Peixuan Guo
Folate receptor is a cell surface glycoprotein highly expressed on cancer cells while its expression on normal cells is low or undetectable (Zwicke et al., 2012). Therefore, folate (FA) has been extensively investigated and applied for the selective delivery of therapeutics to cancers, including breast cancer (Fasehee et al., 2016), lung cancer (Shi et al., 2015), ovarian cancer (van Dam et al., 2011), colorectal cancer (Cisterna et al., 2016), and head and neck cancer (Saba et al., 2009). Conjugation of FA to therapeutic molecules, like chemotherapy drugs (Lee et al., 2009; Yang et al., 2013) has been shown to enhance their targeting and delivery to folate receptor-expressing cancer cells, making FA a superior target for a variety of cancers. However, endosome trapping of folate receptor-mediated endocytosis has been a major hurdle in clinical trial with FA-conjugated therapeutics such as siRNA (Turek et al., 1993; Leamon & Reddy, 2004; Sabharanjak & Mayor, 2004). The therapeutic efficiency is often compromised due to entrapment in endosomes after endocytosis.
Nanoprobes for Early Diagnosis of Cancer
Published in Klaus D. Sattler, st Century Nanoscience – A Handbook, 2020
Active targeting uses peptides and other biomolecules as targeting agents to selectively and successfully transport nanoprobes to cancerous tissue. Generally, passive targeting facilitates the efficient localization of nanoprobes in the tumor interstitium but cannot further promote their uptake by cancer cells. However, in terms of active targeting, specific interactions between the targeting agents on the surface of nanoprobes and receptors expressed on the tumor cells can facilitate nanoprobe’s internalization by triggering receptor-mediated endocytosis. For instance, folate targeting is a classic example of active targeting, as it has been extensively tried and tested over the past years. Folate receptor is overexpressed in a variety of cancer types such as ovarian carcinomas, osteosarcomas, and non-Hodgkin’s lymphomas.12 Nanoprobes conjugated to folate have greater chances of being internalized to a substantial extent, wherein the folate receptors are highly overexpressed.
Polymeric Nanoparticles for Tumor-Targeted Drug Delivery
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Tania Betancourt, Amber Doiron, Lisa Brannon-Peppas
FR are known to be overexpressed in various epithelial cancer cells, such as those of ovarian, mammary gland, colon, lung, prostate, and brain epithelial cancers, and in leukemic cells.49–61 Folate receptor overexpression has been correlated to poor prognosis. In addition, metastasized cancer cells have been found to overexpress the folate receptor to a larger degree than localized tumor cells.62 This finding is of great importance. The only nonpathological tissues where FR is expressed are choroid plexus, placenta, lungs, thyroid, and kidney.46,63 FR expression is limited to the apical (luminal) side of polarized epithelial cells, except for the cells of the proximal tubules in the kidney. As a consequence, FR is practically inaccessible to blood-borne folate-linked systems.44,45 These characteristics make folate receptors very advantageous for targeted delivery of nanoparticles with high payloads of therapeutic agents, imaging agents, and even genes for the treatment, detection, and monitoring of cancer. What is more, the macromolecular size of nanoparticles will prevent gromerular filtration and the consequent exposure of kidney tissue to folate-targeted nanoparticles.
Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Zheng Wang, Minhua Ye, Dehua Ma, Jianfei Shen, Fang Fang
Bombesin and GRP-similar peptides have been implicated as growth factors in various kinds of carcinoma over the last two decades. Most of the lung cancer tissues overexpress the gastrin-releasing peptide receptors [41–44]. Several bombesin derivatives with solid potential for GRPR have explored in clinical investigations for specific receptors treatment and imaging. Radionuclide imaging of lung cancers has been successfully performed using radio-bombesin analogues in clinical trials [45–47]. Therefore, HEL-299 human lung cells have been utilized as tumour models to assess novel bombesin probes [48]. A membrane-bound protein with a great affinity for binding and delivering folate into cells, folate receptor-α (FR-α) is a folate receptor. Enhanced control of cell metabolism, folate is also involved in DNA synthesis and repair and cellular respiration. Antifolates are often used in cancer treatment because cancer cells, which quickly increase, have higher folate requirements to retain DNA engineering. All lung cancer subtypes and overexpress FRs. FRs are significantly expressed in HEL-299 cells, according to current polymerase chain reaction (PCR) investigations [49–52].
Folic acid-modified β-cyclodextrin nanoparticles as drug delivery to load DOX for liver cancer therapeutics
Published in Soft Materials, 2019
Wenbo Fan, Yuedi Xu, Zheng Li, Qiang Li
Folic acid (FA) is a vitamin that is usually used as targeting ligands for cancer nanotechnology, because it binds selectively the folate receptor (FR) which is found to be overexpressed on the surfaces of a significant number of human cancers, including breast, ovarian, liver, lung, and brain metastases.[18,19] The FA–FR complex can be absorbed by cells and moves through many organelles involved in endocytic trafficking. Moreover, FA has the ability to react with various molecules while keeping high stability and low immunogenic property. So, many researches are focused on conjugation of FA to the DDS in order to fully exploit FA’s potential as a targeting ligand.[20–22] Upon the FR interaction, drugs can be delivered to the target tissue efficiently. The FA-conjugated β-CD NPs (FA–β-CD/Ada–DOX NPs), with average size of 1.5–2.5 nm, could target to human hedgehog interacting protein, and the efficiency of DOX delivery to FR cancer cells is eightfold higher than that of nontargeted drug complexes.[23] These targeted drug complexes have high drug association and controlled drug release properties with excellent biocompatibility and physiological stability.
Folate receptor-specific cell-cell adhesion by using a folate-modified peptide-based anchor
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Hiroko Nagai, Wataru Hatanaka, Masayoshi Matsuda, Akihiro Kishimura, Yoshiki Katayama, Takeshi Mori
Here we designed a peptide anchor with a folate through oligoethylene glycol (OEG) spacer (Figure 1). This molecule can be synthesized by straightforward solid phase peptide synthesis. The peptide sequence shown in blue, Lys-Lys(pal)-Lys-Lys-Lys(pal), is the membrane anchoring motif, which was found to be the best sequence in duration time of presentation in our previous report [7]. One of receptors for folate, folate receptor α (FRα), is highly expressed on some kinds of cancer cells [8]. Binding affinity of folate to FRα is relatively high; dissociation constants (Kd) = 0.1 nM [9]. The peptide anchor was labelled with nitrobenzofurazan (NBD) on ε-amine group of L-Lys residue. We utilized the peptide anchor for cell-cell adhesion via ligand-receptor specific interaction.