In recent years, various nanomaterials have emerged as an exciting tool in cancer theranostic applications due to their multifunctional property and intrinsic molecular property aiding effective diagnosis, imaging, and successful therapy. However, chemically synthesized nanoparticles have several issues related to the cost, toxicity and effectiveness. In this context, bio-inspired nanoparticles (NPs) held edges over conventionally synthesized nanoparticles due to their low cost, easy synthesis and low toxicity. In this present review article, a detailed overview of the cancer theranostics applications of various bio-inspired has been provided. This includes the recent examples of liposomes, lipid nanoparticles, protein nanoparticles, inorganic nanoparticles, and viral nanoparticles. Finally, challenges and the future scopes of these NPs in cancer therapy and diagnostics applications are highlighted.
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Recent times have witnessed an upsurge in the incidence of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Prion disease, and amyotrophic lateral sclerosis. The treatment of the same remains a daunting challenge due to the limited access of therapeutic moieties across the blood–brain barrier. Engineered nanoparticles with a size less than 100 nm provide multifunctional abilities for solving these biomedical and pharmacological issues due to their unique physico‐chemical properties along with capability to cross the blood–brain barrier. Needless to mention, there is a scarcity of review articles summarizing recent developments of various nanomaterials including liposomes, polymeric nanoparticles, metal nanoparticles, and bio‐nanoparticles toward the therapeutic and theranostics applications for various neurodegenerative disorders. Here, a broad spectrum of nanomedicinal approaches to eradicate neurodegenerative disorders is provided, along with a brief account of neuroprotection and neuronal tissue regeneration, current clinical status, issues related to safety, toxicity, challenges, and future outlook.
Angiogenesis is a process of generation of de-novo blood vessels from already existing vasculature. It has a crucial role in different physiological process including wound healing, embryonic development, and tumor growth. The methods by which therapeutic drugs inhibit tumor angiogenesis are termed as anti-angiogenesis cancer therapy. Developments of angiogenic inhibiting drugs have various limitations causing a barrier for successful treatment of cancer, where angiogenesis plays an important role. In this context, investigators developed novel strategies using nanotechnological approaches that have demonstrated inherent antiangiogenic properties or used for the delivery of antiangiogenic agents in a targeted manner. In this present article, we decisively highlight the recent developments of various nanoparticles (NPs) including liposomes, lipid NPs, protein NPs, polymer NPs, inorganic NPs, viral and bio-inspired NPs for potential application in antiangiogenic cancer therapy. Additionally, the clinical perspectives, challenges of nanomedicine, and future perspectives are briefly analyzed.
Clear cell renal cell carcinoma (ccRCC) is known for its highly vascular phenotype which is associated with elevated expression of vascular endothelial growth factor A (VEGF), also known as vascular permeability factor (VPF). Accordingly, VEGF has been an attractive target for antiangiogenic therapies in ccRCC. Two major strategies have hitherto been utilized for VEGF-targeted antiangiogenic therapies: targeting VEGF by antibodies, ligand traps or aptamers, and targeting the VEGF receptor signaling via antibodies or small-molecule tyrosine-kinase inhibitors (TKIs). In the present article we utilized two entirely different approaches: targeting mammalian target of rapamycin (mTOR) pathway that is known to be involved in VEGF synthesis, and disruption of VEGF/Neuroplin-1 (NRP1) axis that is known to activate proangiogenic and pro-tumorigenic signaling in endothelial and tumor cells, respectively. Everolimus (E) and a small-molecule inhibitor EG00229 (G) were used for the inhibition of mTOR and the disruption of VEGF/NRP1 axis, respectively. We also exploited a liposomal formulation decorated with a proprietary tumor-targeting-peptide (TTP) to simultaneously deliver these two agents in a tumor-targeted manner. The TTP-liposomes encapsulating both Everolimus and EG00229 (EG-L) demonstrated higher in vitro and in vivo growth retardation than the single drug-loaded liposomes (E-L and G-L) in two different ccRCC models and led to a noticeable reduction in lung metastasis in vivo. In addition, EG-L displayed remarkable inhibition of tumor growth in a highly aggressive syngeneic immune-competent mouse model of ccRCC developed in Balb/c mice. Taken together, this study demonstrates an effective approach to achieve improved therapeutic outcome in ccRCC.
Background: Renal cell carcinoma (RCC) is notorious for its resistance towards chemotherapy and radiation therapy in general. Combination therapy is often helpful in alleviating the resistance mechanisms by targeting multiple signaling pathways but is usually more toxic than monotherapy. Co-encapsulation of multiple therapeutic agents in a tumor-targeted drug delivery platform is a promising strategy to mitigate these limitations. Methods: A tumor-targeted liposomal formulation was prepared using phospholipids, cholesterol, DSPE-(PEG) 2000 -OMe and a proprietary tumor-targeting-peptide (TTP)-conjugated lipopeptide. An efficient method was optimized to encapsulate everolimus and vinorelbine in this liposomal formulation. Single drug-loaded liposomes were also prepared for comparison. Finally, the drug-loaded liposomes were tested in vitro and in vivo in two different RCC cell lines. Results: The tumor-targeted liposomal formulation demonstrated excellent tumor-specific uptake. The dual drug-loaded liposomes exhibited significantly higher growth inhibition in vitro compared to the single drug-loaded liposomes in two different RCC cell lines. Similarly, the dual drug-loaded liposomes demonstrated significantly higher suppression of tumor growth compared to the single drug-loaded liposomes in two different subcutaneous RCC xenografts. In addition, the dual drug-loaded liposomes instigated significant reduction in lung metastasis in those experiments. Conclusion: Taken together, this study demonstrates that co-delivery of everolimus and vinorelbine with a tumor-targeted liposomal formulation is an effective approach to achieve improved therapeutic outcome in RCC.
Since its first clinical application, methotrexate (MTX) has been widely used for the treatment of human diseases. Despite great advantages, some properties such as poor absorption, short plasma half-life and unpredictable bioavailability have led researchers to seek novel delivery systems to improve its characteristics for parenteral and oral administration. Recently, great attention has been directed to hydrogels for the preparation of MTX formulations. This review describes the potential of hydrogels for the formulation of MTX to treat cancer, rheumatoid arthritis, psoriasis and central nervous system diseases. We will delineate the state-of-the-art and promising potential of hydrogels for systemic MTX delivery as well as transdermal delivery of the drug-using hydrogel-based formulations.
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