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      Lipid-Based Drug Delivery Nanoplatforms for Colorectal Cancer Therapy

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          Abstract

          Colorectal cancer (CRC) is a prevalent disease worldwide, and patients at late stages of CRC often suffer from a high mortality rate after surgery. Adjuvant chemotherapeutics (ACs) have been extensively developed to improve the survival rate of such patients, but conventionally formulated ACs inevitably distribute toxic chemotherapeutic drugs to healthy organs and thus often trigger severe side effects. CRC cells may also develop drug resistance following repeat dosing of conventional ACs, limiting their effectiveness. Given these limitations, researchers have sought to use targeted drug delivery systems (DDSs), specifically the nanotechnology-based DDSs, to deliver the ACs. As lipid-based nanoplatforms have shown the potential to improve the efficacy and safety of various cytotoxic drugs (such as paclitaxel and vincristine) in the clinical treatment of gastric cancer and leukemia, the preclinical progress of lipid-based nanoplatforms has attracted increasing interest. The lipid-based nanoplatforms might be the most promising DDSs to succeed in entering a clinical trial for CRC treatment. This review will briefly examine the history of preclinical research on lipid-based nanoplatforms, summarize the current progress, and discuss the challenges and prospects of using such approaches in the treatment of CRC.

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          Most cited references191

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          Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota

          The gut microbiota can be altered by dietary interventions to prevent and treat various diseases. However, the mechanisms by which food products modulate commensals remain largely unknown. We demonstrate that plant-derived e xosomes- l ike n anoparticles (ELNs) are taken up by the gut microbiota and contain RNAs that alter microbiome composition and host physiology. Ginger ELNs (GELNs) are preferentially taken up by Lactobacillaceae in a GELN lipid-dependent manner and contain microRNAs that target various genes in Lactobacillus rhamnosus (LGG). Among these, GELN mdo-miR7267-3p-mediated targeting of the LGG monooxygenase ycnE yields increased indole-3-carboxaldehyde (I3A). GELN RNAs or I3A, a ligand for aryl hydrocarbon receptor (AHR), are sufficient to induce production of IL-22, which is linked to barrier function improvement. These functions of GELN RNAs can ameliorate mouse colitis via IL-22-dependent mechanisms. These findings reveal how plant products and their effects on the microbiome may be used to target specific host processes to alleviate disease. Teng et al. show that exosomes-like nanoparticles (ELNs) from edible plants such as ginger are preferentially taken up by gut bacteria in an ELN lipid dependent manner. ELN RNAs regulate gut microbiota composition and localization as well as host physiology, notably enhancing gut barrier function to alleviate colitis.
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            Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.

            There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
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              Core-shell nanoscale coordination polymers combine chemotherapy and photodynamic therapy to potentiate checkpoint blockade cancer immunotherapy

              Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT). Synergy between oxaliplatin and pyrolipid-induced PDT kills tumour cells and provokes an immune response, resulting in calreticulin exposure on the cell surface, antitumour vaccination and an abscopal effect. When combined with anti-PD-L1 therapy, NCP@pyrolipid mediates regression of both light-irradiated primary tumours and non-irradiated distant tumours by inducing a strong tumour-specific immune response.
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                Author and article information

                Journal
                Nanomaterials (Basel)
                Nanomaterials (Basel)
                nanomaterials
                Nanomaterials
                MDPI
                2079-4991
                21 July 2020
                July 2020
                : 10
                : 7
                : 1424
                Affiliations
                [1 ]Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Digestive Disease Research Group, Georgia State University, Atlanta, GA 30302, USA; dmerlin@ 123456gsu.edu
                [2 ]Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
                Author notes
                [* ]Correspondence: cyang16@ 123456gsu.edu ; Tel.: +1(404)-413-3597; Fax: +1(404)-413-3580
                Author information
                https://orcid.org/0000-0003-0805-1008
                Article
                nanomaterials-10-01424
                10.3390/nano10071424
                7408503
                32708193
                64e8bb3b-b772-4f4e-aeb8-11d0248bdd24
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 July 2020
                : 20 July 2020
                Categories
                Review

                colorectal cancer,lipid-based nanoparticles,targeted drug delivery,plant-derived lipid nanoparticles,exosomes

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