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The Emerging Role of Exosome Nanoparticles in Regenerative Medicine
Published in Harishkumar Madhyastha, Durgesh Nandini Chauhan, Nanopharmaceuticals in Regenerative Medicine, 2022
Zahra Sadat Hashemi, Mahlegha Ghavami, Saeed Khalili, Seyed Morteza Naghib
The therapeutic efficiency of MSC-EVs is hampered by their quick elimination after systemic administration. A hydrogel slow-released system was developed to prolong the EVs retention and maintain their stability. A designed matrix metalloproteinase-2 (MMP2) sensitive self-assembling peptide (KMP2) hydrogel loaded EVs was exploited to deliver locally in mice with renal IRI. The MSC-EVs-loaded KMP2 hydrogel exerted cell apoptosis, inflammation, and angiogenesis effects due to its biologically compatible and nanosize characteristics. These properties promote the microvascular endothelial cell regeneration after IRI (Zhou et al. 2019). Matrix metalloproteinases (MMPs) are zinc end peptidases that act on the degradation of extracellular matrix (ECM) proteins involved in tissue remodelling (Kunugi et al. 2011). MMP-cleavable peptides have been applied in the production of MMP-degradable biomaterial for drug release and tissue repair (Wang et al. 2018b).
Barriers in the Tumor Microenvironment to Nanoparticle Activity
Published in Dan Peer, Handbook of Harnessing Biomaterials in Nanomedicine, 2021
Hanan Abumanhal-Masarweh, Lilach Koren, Omer Adir, Maya Kaduri, Maria Poley, Gal Chen, Aviram Avital, Noga Sharf Pauker, Yelena Mumblat, Jeny Shklover, Janna Shainsky-Roitman, Avi Schroeder
Cancer-associated fibroblasts (CAFs) are a main component in the heterogeneous cells’ complex network within the tumor microenvironment [100]. CAFs are often the dominant cell type within a solid tumor cell population and act as tumor promoters by expressing and secreting various growth factors, metabolites, cytokines and enzymes that induce cancer cells proliferation [101, 102]. In advanced stages of cancer, these cells produce matrix metalloproteinases (MMPs) leading to ECM degradation, thus enabling cancer cell’ motility and invasion [103, 104]. On the other hand, CAFs overexpressing ECM components such as fibronectin and collagen increase ECM rigidity due to cross-linking [105, 106]. As a result of ECM stiffness along with tumor solid stress, drug molecules and nanoparticles effective uptake and penetration into cancer cells is hindered [107].
Tunable Hydrogel Systems for Delivery and Release of Cell-Secreted and Synthetic Therapeutic Products
Published in Emmanuel Opara, Controlled Drug Delivery Systems, 2020
Kylie G. Nairon, Thomas DePalma, Hemamylammal Sivakumar, Aleksander Skardal
Disease and injury states are often marked by a local increase in cytokines, enzymes, and other biochemical signals. When designed with enzymatically cleavable motifs, hydrogels can become susceptible to enzymatic degradation specific to the disease state it is intended to treat. This method is especially attractive in cell-based therapies to enable self-remodeling of the hydrogel matrix.59 Matrix metalloproteinases (MMPs) are a family of enzymes capable of cleaving many ECM components, such as collagen and GAGs, and play a major role in cellular remodeling, and are thus upregulated in environments including cancerous tumors and soft tissue wounds.60 MMP-cleavable crosslinkers can be customized to the MMPs specific to an injury or disease state, inducing environment-controlled hydrogel degradation.61
The emergence of nanoporous materials in lung cancer therapy
Published in Science and Technology of Advanced Materials, 2022
Deepika Radhakrishnan, Shan Mohanan, Goeun Choi, Jin-Ho Choy, Steffi Tiburcius, Hoang Trung Trinh, Shankar Bolan, Nikki Verrills, Pradeep Tanwar, Ajay Karakoti, Ajayan Vinu
Enzyme sensitive functional nanoporous materials have been explored for lung cancer therapy as well. In fact, matrix-metalloproteinases (MMPs) are overexpressed in many types of cancer. This targeted approach can be applied for obtaining enhanced bioavailability through guided therapeutic targeting. To realize this strategy, MMP responsive NPs based on a functionalised copolymer mPEG-Peptide-PCL was used along with curcumin drug and were well internalized into cancer cells through macropinocytosis. The pharmacodynamics and cellular internalization analysis in vitro, and in vivo biodistribution studies confirmed that these enzyme responsive curcumin loaded nanoparticles showed better targetability and thus improved therapeutic outcome than the intact curcumin in the tumour tissue [344].
Understanding the complex microenvironment in oral cancer: the contribution of the Faculty of Dentistry, University of Otago over the last 100 years
Published in Journal of the Royal Society of New Zealand, 2020
Alison Mary Rich, Haizal Mohd Hussaini, Benedict Seo, Rosnah Bt Zain
Interleukin 17 is a pro-inflammatory cytokine with both pro- and anti-tumour effects which has been shown to have increased expression in some cancers. Its pro-tumour effects are mediated by mechanisms including inducing the expression of matrix metalloproteinases (MMPs) in tumour cells and/or stimulating increased tumour angiogenesis. The anti-tumour effects of IL17 are exerted through increased Tc cells and IFNγ activity. Our studies showed significantly more IL17+ cells were present in the TME of OSCC than inflammatory controls (Avadhani 2015). Double-labelling immunofluorescence studies revealed that Th cells, Tc cells, macrophages and mast cells co-expressed IL17 (Avadhani et al. 2017). Using an extracellular matrix (ECM) cell invasion assay kit with invasion assay chambers we found that IL17 significantly promoted the in vitro invasion of OSCC cell lines (Avadhani 2015). These results are consistent with the observations in other cancers where IL17 was found to facilitate tumour progression e.g. breast cancer cell lines, cervical cancer cell lines (Cochaud et al. 2013; Punt et al. 2015).
Functional biomimetic nanoparticles for drug delivery and theranostic applications in cancer treatment
Published in Science and Technology of Advanced Materials, 2018
Lei Li, Junqing Wang, Hangru Kong, Yun Zeng, Gang Liu
The extracellular matrix metalloproteinase (MMP) proteolytic enzymes are usually overexpressed in many types of tumors and play an important role in invasion and metastasis of cancer. MMP-2 and MMP-9 have been investigated as a trigger to chemically modulate the drug delivery from the carriers. Mallik et al. [130] developed the nanovesicles, which are responsive to overexpression of glutathione (GSH) and MMP-9 in the tumor microenvironment to deliver the anticancer drug gemcitabine (Gem) efficiently and selectively. Mallik et al. synthesized an MMP-9-cleavable, collagen mimetic lipopeptide which forms nanosized vesicles with the 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC), PEGylated 1-palmitoyl-2-oleoyl-snglycerosnglycero-3-phosphoethanolamine lipid (POPE-SS-PEG), and cholesteryl-hemisuccinate lipids as shown in Figure 9. In the tumor microenvironment, the increased glutathione reductively could remove the PEG groups, exposing the lipopeptides to MMP-9. The resultant destabilization of the lipid bilayer led to rapid release of encapsulated anticancer drug Gem. By using pancreatic cancer cell spheroids, internalization studies showed that the incorporated MMP-9-responsive lipopeptide triggers the drug release in the tumor’s extracellular matrix. Live animal imaging study confirmed the stability of the long-circulating nanovesicles. In vivo studies by employing a xenograft mouse model of human pancreatic cancer also confirmed the release of encapsulated gemcitabine in the tumor site and a reduction in tumor growth was observed in these nude mice.