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    Chitosan-based nanoscale systems for doxorubicin delivery: Exploring biomedical application in cancer therapy
    (AICHE Online Library, 2022) Ashrafizadeh, Milad; Hushmandi, Kiavash; Mirzaei, Sepideh; Bokaie, Saied; Bigham, Ashkan; Makvandi, Pooyan; Rabiee, Navid; Thakur, Vijay Kumar; Kumar, Alan Prem; Sharifi, Esmaeel; Varma, Rajender S.; Aref, Amir Reza; Wojnilowicz, Marcin; Zarrabi, Ali; Karimi-Maleh, Hassan; Voelcker, Nicolas H.; Mostafavi, Ebrahim; Orive, Gorka
    Green chemistry has been a growing multidisciplinary field in recent years showing great promise in biomedical applications, especially for cancer therapy. Chitosan (CS) is an abundant biopolymer derived from chitin and is present in insects and fungi. This polysaccharide has favorable characteristics, including biocompatibility, biodegradability, and ease of modification by enzymes and chemicals. CS-based nanoparticles (CS-NPs) have shown potential in the treatment of cancer and other diseases, affording targeted delivery and overcoming drug resistance. The current review emphasizes on the application of CS-NPs for the delivery of a chemotherapeutic agent, doxorubicin (DOX), in cancer therapy as they promote internalization of DOX in cancer cells and prevent the activity of P-glycoprotein (P-gp) to reverse drug resistance. These nanoarchitectures can provide co-delivery of DOX with antitumor agents such as curcumin and cisplatin to induce synergistic cancer therapy. Furthermore, co-loading of DOX with siRNA, shRNA, and miRNA can suppress tumor progression and provide chemosensitivity. Various nanostructures, including lipid-, carbon-, polymeric- and metal-based nanoparticles, are modifiable with CS for DOX delivery, while functionalization of CS-NPs with ligands such as hyaluronic acid promotes selectivity toward tumor cells and prevents DOX resistance. The CS-NPs demonstrate high encapsulation efficiency and due to protonation of amine groups of CS, pH-sensitive release of DOX can occur. Furthermore, redox- and light-responsive CS-NPs have been prepared for DOX delivery in cancer treatment. Leveraging these characteristics and in view of the biocompatibility of CS-NPs, we expect to soon see significant progress towards clinical translation.
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    Customizing nano-chitosan for sustainable drug delivery
    (PMC, 2022) Mostafa Saeedi 1, Omid Vahidi 1, Mohammadreza Moghbeli 1, Sepideh Ahmadi 2, Mohsen Asadnia 3, Omid Akhavan 4, Farzad Seidi 5, Mohammad Rabiee 6, Mohammad Reza Saeb 7, Thomas J Webster 8, Rajender S Varma 9, Esmaeel Sharifi 10, Ali Zarrabi 11, Navid Rabiee 12 Affiliations collapse; Saeedi, Mostafa; Vahidi, Omid; Moghbeli, Mohammadreza; Ahmadi, Sepideh; Asadnia, Mohsen; Akhavan, Omid; Seidi, Farzad; Rabiee, Mohammad; Saeb, Mohammad Reza; Webster, Thomas J.; Zarrabi, Ali; Rabiee, Navid; Varma, Rajender S.; Sharifi, Esmaeel
    Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, the various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article
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    Gene editing-based technologies for beta-hemoglobinopathies treatment
    (MDPI, 2022) Rahimmanesh, Ilnaz; Boshtam, Maryam; Kouhpayeh, Shirin; Khanahmad, Hossein; Dabiri, Arezou; Ahangarzadeh, Shahrzad; Esmaeili, Yasaman; Bidram, Elham; Vaseghi, Golnaz; Haghjooy, Shaghayegh; Shariati, Laleh; Zarrabi, Ali; Varma, Rajender S.
    Simple Summary: ?-thalassemia syndromes are clinically and genetically heterogeneous blood disorders presented by ?-chain deficiency in hemoglobin production. Despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, which have been recently applied to improve ?-thalassemia symptoms. Nevertheless, several obstacles, such as off-target effects, protospaceradjacent motif requirement, efficient gene transfer and expression methods, DNA-damage toxicity, and immunotoxicity issues still need to be addressed in order to improve the safety and efficacy of the gene editing approaches. Hence, additional efforts are needed to address these problems, evaluate the safety of genome editing tools at the clinical level and follow the outcomes of gene editing tools-mediated therapeutic approaches in related patients. Abstract: Beta (?)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the ?-globin chains in hemoglobin structure. Traditional treatment for ?-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat–Cas-associated nucleases. These tools have concentrated on ?- or ?-globin addition, regulating the transcription factors involved in expression of endogenous ?-globin such as KLF1, silencing of ?-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for ?-thalassemia treatment and paving the way for patients’ therapy.
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    Sustainable synthesis: natural processes shaping the nanocircular economy
    (Royal Soc Chemistry, 2024) Khosravi, Arezoo; Zarepour, Atefeh; Iravani, Siavash; Varma, Rajender S.; Zarrabi, Ali
    Sustainable synthesis in nano domain refers to the development of nanomaterials through deployment of natural processes and principles to minimize the use of hazardous materials and reduce the generation of waste. This method aims to mitigate the environmental impact associated with traditional synthesis methods wherein natural processes, such as biomineralization and self-assembly, offer valuable insights into the nanocircular economy (NE) thus creating numerous benefits. Firstly, it reduces the environmental footprint of nanotechnology by minimizing energy consumption and waste generation. Secondly, it promotes the efficient use of resources by incorporating principles of recycling and reusability. By mimicking natural processes, various nanomaterials can be created, which are biocompatible, biodegradable, and less harmful to the environment. However, challenges such as scale-up, cost, regulatory frameworks, and material selection ought to be addressed to ensure their widespread adoption. The prospects for sustainable synthesis in the NE are promising, with potential advancements in advanced materials, and the integration of circular economy concepts into nanomedicine, and environmental appliances; its future lies in bioinspired synthesis, adherence to green chemistry principles, waste recycling and up-cycling, energy-efficient techniques, life cycle assessment (LCA), and multi-disciplinary collaborations. This review seeks to contribute to the existing knowledge and understanding of sustainable synthesis and its impact on shaping eco-friendlier and resource-efficient NE by describing the methodology involved and discuss the benefits, challenges, and future opportunities emphasizing the importance of sustainability and responsible practices in development of nanomaterials. This perspective aims to shed light on the transformative potential of sustainable synthesis in guiding the transition towards circular economy conceptions in the nanotechnology domain.