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Nanotoxicology and Regulatory Aspects of Nanomaterials and Nanomedicines
Published in Yasser Shahzad, Syed A.A. Rizvi, Abid Mehmood Yousaf, Talib Hussain, Drug Delivery Using Nanomaterials, 2022
Caveolin-dependent endocytosis is a process of internalization of small particles and fluids through membrane invaginations as flask-shaped vesicles. It is commonly abundant in endothelial linings facilitating the extravasation of serum proteins and nutrients to the surrounding tissues. Caveolae are triggered through certain receptors, i.e., serum albumin gp60. Subsequent signalling cascade through Src tyrosine kinase activates phosphorylation and formation of Caveolin-1; a dimeric protein that forms a coating of caveolin striations around certain cholesterol/sphingolipids-rich bindings on the inner membrane layer. Caving-in or invaginating membranous vesicles ensues with the contraction of dynamin and dynamin arrangement by the actin cytoskeleton forming caveosomes (Conner and Schmid, 2003). Caveosomes have neutral pH and bypass the lysosomes protecting its package from degradation with subcellular smooth ER and cytosolic delivery. This route has been used by some pathogens and bacteria to evade lysosomal degradation (Pelkmans et al., 2001), and has been under investigations to enhance NPs internalization (Dauty et al., 2002). Caveolae have many biological roles, such as lipid and cholesterol hemostasis, regulating some cellular cascades, regulating endothelial NO synthase, and transcellular transport of serum albumin and nutrients (Cohen et al., 2004; Parton and Del Pozo, 2013). Caveolae involve transport small fluid vesicles of ~80 nm (Foroozandeh and Aziz, 2018).
Active Nanoparticle Targeting: Current Status and Future Challenges
Published in Sandeep Nema, John D. Ludwig, Parenteral Medications, 2019
Siddharth Patel, Janni Mirosevich
The caveolae-mediated pathway represents another well-studied endosomal pathway. Caveolae, through caveolin proteins, have been shown to bind several ligands involved in cell signaling pathways, such as non-receptor tyrosine kinases, insulin receptors, heterotrimeric G proteins, platelet-derived growth factor receptors, and endothelial nitric oxide synthase (Parton and Simons 2007). The resulting caveosomes have a diameter of about 50–100 nm and undergo slower internalization kinetics than CME endosomes (Razani and Lisanti 2002). This internalization pathway has attracted interest because it may avoid lysosomal degradation, thereby making it the preferred route for the delivery of proteins and nucleotides (Le and Nabi 2003). Proteins such as cholera toxin B and Shiga toxin, SV40 viral particles, and nanoparticles such as Abraxane and Doxil are known to undergo caveolae-mediated endocytosis (Montesano et al. 1982; Pelkmans, Püntener, and Helenius 2002; Doherty and McMahon 2009; Gradishar 2006; Sahay et al. 2010).
Antiviral Nanomaterials as Potential Targets for Malaria Prevention and Treatment
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Kantrol Kumar Sahu, Sunita Minz, Madhulika Pradhan, Monika Kaurav, Krishna Yadav
Pinocytosis is classified as caveolae-mediated endocytosis, clathrin-mediated endocytosis clathrin- and caveolae-independent endocytosis, and micropinocytosis (Sun et al. 2019) (Table 18.2). Caveolar-mediated endocytosis is a clathrin-independent endocytotic mechanism involving bulb-shaped caveolae. Caveolae are 50-60 nm plasma membrane invaginations. Caveolae are formed by caveolins, which are integral membrane proteins, and cavins are peripheral membrane proteins. Clathrin-mediated endocytosis possesses complex protein machinery that transiently assembles on the plasma membrane and creates clathrin-coated endocytic vesicles. This machinery selects and concentrates cargo molecules and shapes the membrane into a vesicle.
Synthesis and characterization of magnetic nanoparticles coated with polystyrene sulfonic acid for biomedical applications
Published in Science and Technology of Advanced Materials, 2020
Bo-Wei Chen, Yun-Chi He, Shian-Ying Sung, Trang Thi Huynh Le, Chia-Ling Hsieh, Jiann-Yeu Chen, Zung-Hang Wei, Da-Jeng Yao
To compare the internalization of PSS-MNPs between normal and tumor cells, we used NIH-3T3 fibroblasts and SK-HEP1 HCC cells as a proof-of-principle demonstration. Our results of the quantification of MNPs uptaken by cells (Figure 4) provide evidence that PSS-MNPs are more accessible in tumor cells, which might benefit from targeting of cancers. Although the mechanism underlying the preferential internalization of PSS-MNPs into the SK-HEP1 cells remains to be determined, the nanoparticle size and surface coating have been known to be key determinants of the uptake pathways [41,42]. Other than particle size, it is, in general, assumed that anionic nanoparticles appear to be mainly taken up by caveolae-mediated endocytosis. Caveolae are plasma membrane invaginations with size in a range typically from 50 to 100 nm and are composed of membrane protein caveolin, which confers on them a flask-shaped structure. Among three known caveolins (CAV-1, 2 and 3), caveolin-1 (CAV-1) is ubiquitously expressed in all cell types and was found to be over-expressed in numerous cancers in which it can act as a positive regulator of stress resistance and survival [43]. A recent meta-analytical study [44] supported that CAV-1 is correlated with an unfavorable clinico-pathological status of HCC, including a low degree of differentiation and metastasis. Based on the particle size and surface charge, the high rate of PSS-MNP internalization in SK-HEP1 HCC cells occurs, perhaps, through the enhanced caveolae-mediated endocytosis pathway that is contributed by the over-expressed CAV-1 on the cells. This feature in combination with greater saturation magnetization 60 emu g−1 Fe3O4 makes the present PSS-MNPs superior to previously reported MNPs coated with polymers of other types, including PEG [45–47], DEX [47–49], PVP [50] and PVA [51] for HCC theranostics with an applied magnetic field. We are currently optimizing the protocol of enhanced stability and cargo encapsulation. With these improvements, a further assessment of PSS-MNP-mediated drug delivery or hyperthermia for the treatment of HCC is thereby warranted.