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Advantages and Limitations of RNAi Delivery for Cancer Biological Therapeutics Imaging
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
We report on bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted CT imaging and chemotherapy of MCF-7 human breast tumor (Scheme 7.1). HAI-NGs were obtained from hyaluronic acid-cystamine-tetrazole (HA-Cys-Tet) and reductively degradable polyiodixanol-methacrylate (SS-PI-MA) via nanoprecipitation and a photo-click crosslinking reaction. HAI-NGs were designed with the following unique features: (i) both HA and iodixanol have excellent biocompatibility and are currently used in the clinic; (ii) the “tetrazole-ene” photo-click crosslinking reaction is highly selective, which prevents cross-reaction with most drugs and furthermore endows nanogels with bright green fluorescence [210,211]; (iii) HA can actively target CD44 receptors which are overexpressed on various malignant tumor cells and stem cells [212–215]; (iv) HAI-NGs can be used for targeted CT imaging in vivo; and (v) the reduction-sensitivity of HAI-NGs allows fast intracellular release of payloads like PTX to achieve efficient and targeted chemotherapy. Tetrazole (Tet) and cystamine diisocyanate (CDI) were synthesized according to previous reports [210,216]. Herein, the stability of HAI-NGs and the reduction-triggered PTX release from PTX loaded HAI-NGs were investigated. Furthermore, the targetability of HAI-NGs and antitumor activity of PTX loaded HAI-NGs toward MCF-7 cells, the pharmacokinetics and biodistribution, NIR and CT imaging, as well as therapeutic effects in MCF-7 human breast tumor xenografts in mice were evaluated.
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
HA is known to play an important role in cellular adhesion, migration, invasion, proliferation, and angiogenesis by binding to the CD44 receptor and HA-mediated motility (RHAMM). CD44 overexpression in cancer cell lines is also considered to be associated with drug-resistant cancer and considered to have prognostic value for the identification of lung, ovarian and other forms of cancer. This known pharmacological significance of HA makes it an interesting molecule for being used in nanodrug delivery applications. As a result, the HA-DSPE system was developed, which was used for the development of paclitaxel-encapsulated HA-DSPE (PTX-HA-DSPE) NPs of 114 nm size. It was reported to be effective against ovarian cancer [133]. Similarly, paclitaxel-encapsulated HA-cholanic acid NPs were also developed for the treatment of head and neck cancer [134, 135].
Recent Advances with Targeted Liposomes for Drug Delivery
Published in Vladimir Torchilin, Handbook of Materials for Nanomedicine, 2020
Josimar O. Eloy, Raquel Petrilli, Fabíola Silva Garcia Praça, Marlus Chorilli
Other cancer targets have been also explored for aptamer-mediated liposomal delivery. EGFR aptamers have been evaluated for the delivery of erlotinib to lung cancer, with some promising results in reversing the hypoxia drug resistance both in vitro and in vivo (F. Li, Mei, Xie, et al. 2017; F. Li, Mei, Gao, et al., 2017). Another target with great potential for clinical application is the CD44 receptor, which is one of the most common cancer stem cell surface markers of a variety of tumors. Alshaer and collaborators, in 2015, synthesized anti-CD44 liposomes based on a thiol-maleimide reaction. Flow cytometry and confocal microscopy revealed high selectivity and sensitivity for binding CD44 positive cell lines (Alshaer et al., 2015). More recently, the same research group published a paper on aptamer-guided liposomes for selective delivery of siRNA to CD44-expressing breast cancer cells. It was demonstrated the ability of siRNA to silence luciferase gene both in vitro and in vivo (Alshaer et al., 2018).
Formulation and evaluation of a two-stage targeted liposome coated with hyaluronic acid for improving lung cancer chemotherapy and overcoming multidrug resistance
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Xuelian Wang, Hongye Cai, Xinyu Huang, Zhuhang Lu, Luxi Zhang, Junjie Hu, Daizhi Tian, Jiyu Fu, Guizhi Zhang, Yan Meng, Guohua Zheng, Cong Chang
Additionally, the endocytosis of HA/TT LP/C6 was assessed using several inhibitors, including indomethacin, chlorpromazine, amiloride and HA. Specifically, the selection of indomethacin, chlorpromazine, and amiloride was based on their known effects on the caveolin-dependent, clathrin-dependent, and macropinocytosis pathways of endocytosis. HA is a specific ligand of CD44 receptors, which are overexpressed on the cell membrane of many solid cancer cells, including NSCLC. The interaction between HA and CD44 receptors has been investigated as a potential target for drug delivery to cancer cells. As shown in Figure 6A, the factors that most influenced intracellular fluorescence intensity were HA, chlorpromazine, indomethacin, and amiloride in that order, indicating that the endocytic pathways of HA/TT LP/C6 were primarily mediated by CD44 receptors, followed by clathrin-mediated, caveolin-mediated, and macropinocytosis pathways.
Injectable enzyme-catalyzed crosslinking hydrogels as BMSCs-laden tunable scaffold for osteogenic differentiation
Published in Journal of Biomaterials Science, Polymer Edition, 2023
Hongwei Pan, Wanxin Li, Yue Qu, Simei Li, Ayixiemu Yusufu, Jia Wang, Lihua Yin
Hyaluronic acid (HA), a biodegradable, non-immunogenic, and non-inflammatory natural linear polysaccharide, is the main component of the extracellular matrix and composes of N-acetyl-D-glucosamine and D-glucuronic acid, and is widely distributed in connective tissue, epithelial tissue, nerve tissue, and other tissues. It can interact with CD44 to regulate cell movement and adhesion and promote osteogenic differentiation of stem cells [4, 24, 25]. However, the turnover of HA is fast, and a large number of HA body component is degraded and remodeled every day, so HA needs to be modified to increase mechanical stability for tissue engineering [26]. In previous studies, Tyr-modified HA (HA-Tyr) has been introduced as an enzyme crosslinked hydrogel for drug delivery and tissue engineering [27–29]. Cells can combine, proliferate and spread with HA-Tyr through HA-bound cell surface proteins, which makes it a scaffold material suitable for cell encapsulation and tissue engineering [30, 31]. However, these hydrogels have shortcomings, such as limited mechanical properties and rapid degradation, which dramatically limits their application. Although mechanical properties and degradability can be improved by increasing horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) concentrations, this will increase cytotoxicity and potentially induce immune responses [31–33]. Thus, HA hydrogels can benefit from composite systems that enhance mechanical properties and degradation resistance.
Carbon-based nanomaterials as scaffolds in bone regeneration
Published in Particulate Science and Technology, 2020
Liana Crisan, Bogdan Vasile Crisan, Simion Bran, Florin Onisor, Gabriel Armencea, Sergiu Vacaras, Ondine Patricia Lucaciu, Ileana Mitre, Mihaela Baciut, Grigore Baciut, Cristian Dinu
The cellular adhesion molecule CD44 is a receptor of the surface of the cell membrane which achieves the connection between various components of the extracellular matrix and cell surface (Hayer et al. 2005). CD 44 is known as a homing lymphocyte receptor. The major physiological role of CD44 is the maintenance of tissue homeostasis, making connections between the components of extracellular matrix (collagen, fibronectin, chondroitin sulfate, and collagen type I) and a cell surface protein – osteopontin. This glycoprotein is intensely expressed by osteocytes, while osteoblasts are negative for this marker. Periosteal cells and osteoclast cells also express CD44, but not as intensely as osteocytes (Hughes et al. 1994). The location of such glycoproteins was evidenced by immunohistochemical studies. In round osteoblasts, attached to the surface of the bone, the immunoreactivity is strictly at the level of the plasmatic membrane, and osteocytes incorporated into bone matrix expresses the intense level of CD44 at the level of plasmatic membrane. These findings suggest that the osteoblastic line expresses CD44 more intensely as it is transforming into osteocytes (Nakamura et al. 1995).