An In Vitro Assessment of Novel chitosan/bimetallic PtAu Nanocomposites As Delivery Vehicles for Doxorubicin

2020

Biomedicines

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The development of a biocompatible and nontoxic gene delivery vehicle remains a challenging task. Selenium nanoparticles (SeNPs) have the potential to increase delivery efficiency, to reduce side effects, and to improve therapeutic outcomes. In this study, chitosan (Ch) functionalized folate (FA)-targeted SeNPs were synthesized, characterized, and evaluated for their potential to bind, protect, and safely deliver Fluc-siRNA in vitro. SeNPs of less than 100 nm were successfully synthesised and further confirmed using UV-vis and Fourier transform infrared spectroscopy, transmission electron microscopy, and nanoparticle tracking analysis. Cell viability studies were conducted in vitro in selected cancer and non-cancer cell lines. Folate receptor (FOLR1) targeted and nontargeted luciferase gene silencing studies were assessed in the transformed Hela-tat-Luc cell line expressing the luciferase gene. Targeted and nontargeted SeNP nanocomplexes showed minimal toxicity in all cell lines at selected w/w ratios. Maximum gene silencing was achieved at optimum w/w ratios for both nanocomplexes, with Selenium-chitosan-folic acid (SeChFA) nanocomplexes showing slightly better transgene silencing, as supported by results from docking studies showing that SeChFA nanocomplexes interacted strongly with the folate receptor (FOLR1) with high binding energy of −4.4 kcal mol−1.

Section: Discussionmentioning

confidence: 99%

Polymerized Selenium Nanoparticles for Folate-Receptor-Targeted Delivery of Anti-Luc-siRNA: Potential for Gene Silencing

Maiyo

2020

Biomedicines

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“…The success of therapeutic mRNA delivery has been further hindered by mRNA instability, inefficient delivery and uptake, and limited transfection [10]. Core-shell nanoparticles composed of inorganic and organic materials are efficient delivery vehicles due to their defined physical features, tunable size, and versatile chemical and physical properties, which can be used over a wide range of gene and drug delivery platforms [14][15][16][17], in addition to their multifunctional capabilities, enhanced biocompatibility, and synergistic properties. To date, there are very few reports on their use for mRNA delivery and almost none on an inorganic/organic core shell system.…”

Section: Introductionmentioning

confidence: 99%

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy

Maiyo

2019

Pharmaceuticals

Systemic messenger RNA (mRNA) delivery, although still in its infancy, holds immense potential for application in cancer vaccination and immunotherapy. Its advantages over DNA transfection make it attractive in applications where transient expression is desired. However, this has proved challenging due to mRNA’s instability and susceptibility to degradation. Selenium is important for immune function and modulation, with selenium nanoparticles (SeNPs) finding a niche in biomedicine as drug delivery vehicles, owing to their biocompatibility, low toxicity, and biodegradability. In this investigation, we synthesized chitosan-coated SeNPs with a folic acid targeting moiety for Fluc mRNA delivery to cancer cells in vitro. Synthesized SeNPs were stable and well dispersed, and ranged from 59 to 102 nm in size. Nanoparticles bound and protected mRNA from RNase degradation, while exhibiting low cytotoxicity in the human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7), and nasopharyngeal (KB) cells in culture. Moderate cytotoxicity evidenced in the colorectal carcinoma (Caco-2) and colon carcinoma (HT-29) cells was attributed to apoptosis induction by selenium, as confirmed by acridine orange/ethidium bromide staining. Selenium uptake studies corroborated the transfection results, where significant transgene expression was evident for the overexpressed folate receptor-positive KB cells when compared to the other cells with less or no folate receptors.

“…The large cylindrical pore size (~9-10 nm) and pore volume (1.743321 cm 3 /g) allowed for the easy uptake of DOX into the silica framework, resulting in a high loading capacity of 93% and 98 % in the 2% PCMSN and 5% PCMSN formulations, respectively. This was much higher than a previous report on DOX loading into nanoparticles using a similar method [78]. Due to the many DOX molecules adhered to the PEG coating on the interfacial surface of the MSN, a burst release under physiological conditions (pH 7.4), was evident during the drug release studies.…”

Section: Discussionmentioning

confidence: 61%

“…The cytotoxicity of the MSNs and their drug nanoconjugates in vitro was assessed using the 4,5dimethylthiazol-2,5-diphenyltetrazolium bromide (MTT) assay [103] and methodology followed as per previous publications [40,78,87,104]. All cells were seeded in 96 well plates (containing 100 µL EMEM, 10%FBS and 10% antibiotics), at a density of 1 × 10 4 cells/well and incubated at 37°C in 5% CO 2 for 24 h. Thereafter, the culture medium was replaced, DOX-MSNs (20, 50 and 100 µg/mL) added, and the cells incubated for 48 h. A positive control of untreated cells was included.…”

Section: Mtt Cytotoxicity Assaymentioning

confidence: 99%

Sterically Stabilised Polymeric Mesoporous Silica Nanoparticles Improve Doxorubicin Efficiency: Tailored Cancer Therapy

Moodley

2020

Molecules

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The fruition, commercialisation and clinical application combining nano-engineering, nanomedicine and material science for utilisation in drug delivery is becoming a reality. The successful integration of nanomaterial in nanotherapeutics requires their critical development to ensure physiological and biological compatibility. Mesoporous silica nanoparticles (MSNs) are attractive nanocarriers due to their biodegradable, biocompatible, and relative malleable porous frameworks that can be functionalized for enhanced targeting and delivery in a variety of disease models. The optimal formulation of an MSN with polyethylene glycol (2% and 5%) and chitosan was undertaken, to produce sterically stabilized, hydrophilic MSNs, capable of efficient loading and delivery of the hydrophobic anti-neoplastic drug, doxorubicin (DOX). The pH-sensitive release kinetics of DOX, together with the anticancer, apoptosis and cell-cycle activities of DOX-loaded MSNs in selected cancer cell lines were evaluated. MSNs of 36-60 nm in size, with a pore diameter of 9.8 nm, and a cumulative surface area of 710.36 m 2 /g were produced. The 2% pegylated MSN formulation (PCMSN) had the highest DOX loading capacity (0.98 mg dox /mg msn ), and a sustained release profile over 72 h. Pegylated-drug nanoconjugates were effective at a concentration range between 20-50 µg/mL, inducing apoptosis in cancer cells, and affirming their potential as effective drug delivery vehicles.Molecules 2020, 25, 742 2 of 22 MSNs possess a large active surface area which can be selectively polymerised or functionalised for stimuli-responsive purposes [11], tunable pore size and large pore volumes for the loading and controlled release of the cargo, and have shown favourable tolerance levels both in vitro and in vivo [12][13][14].MSNs are being extensively researched as theranostic devices for diseases, especially for cancer therapy [15]. Conventional cancer treatment options such as surgery, radiotherapy and chemotherapy [16], have not been fully effective, resulting in snowballing recurrence rates and depression in the quality of life [17,18]. Unpleasant side-effects are often linked to the anti-neoplastic drugs used, which act by inhibiting cellular mechanisms of DNA replication that are up-regulated in cancer cells. These cytostatic or cytotoxic compounds usually have low bioavailability and are thus administered at high dosages or for prolonged dosing intervals, leading to systemic side effects at non-specific sites [19,20].Doxorubicin (DOX) remains one of the most efficient anthracycline drugs available and is used in the treatment of diverse cancers, including breast, cervical, bone, gastric and leukaemia [21][22][23]. Despite its popularity, its low solubility [24][25][26], coupled with increased dosing frequencies [27][28][29] has resulted in many associated side effects, including cardiotoxicity [30][31][32], myelosuppression [33,34], induced vomiting with nausea [35,36], and alopecia [18,37]. Critical evaluation of these detrimental side-effects that become more...