The unprecedented success of mRNA-lipid nanoparticles (LNPs) has highlighted their power for protein expression, but the hours-long half-life of mRNA severely limits their use in chronic diseases. In contrast, DNA LNPs display months-long expression and genetically encode cell type specificity, but their use has been hindered by poor protein expression (orders of magnitude lower than mRNA LNPs). To overcome this, we introduce multi-stage mixing (MSM) microfluidics to control the internal structure of LNPs and use it to create core-then-shell (CTS) structured DNA LNPs.
View Article and Find Full Text PDFNanomedicine has long pursued the goal of targeted delivery to specific organs and cell types but has yet to achieve this goal with the vast majority of targets. One rare example of success in this pursuit has been the 25+ years of studies targeting the lung endothelium using nanoparticles conjugated to antibodies against endothelial surface molecules. However, here we show that such "endothelial-targeted" nanocarriers also effectively target the lungs' numerous marginated neutrophils, which reside in the pulmonary capillaries and patrol for pathogens.
View Article and Find Full Text PDFLipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway.
View Article and Find Full Text PDFMultiple studies have shown that the progression of breast cancer depends on multiple signaling pathways, suggesting that therapies with multitargeted anticancer agents will offer improved therapeutic benefits through synergistic effects in inhibiting cancer growth. Dual-targeted inhibitors of phosphoinositide 3-kinase (PI3-K) and histone deacetylase (HDAC) have emerged as promising cancer therapy candidates. However, poor aqueous solubility and bioavailability limited their efficacy in cancer.
View Article and Find Full Text PDFExistence of cancer stem cells (CSCs) are primarily responsible for chemoresistance, cancer reoccurrence and treatment failure in cancer patients. Eliminating CSCs along with bulk tumor is a necessity to achieve complete cancer inhibition. Salinomycin (SAL) has potential to specifically target and kill CSCs through blocking their multiple pathways simultaneously.
View Article and Find Full Text PDFCombination chemotherapy with systemic administration of drugs in their free form can be challenging due to non-synchronized pharmacokinetics and sub-optimal tumor accumulation. The present study investigates a PLA-based block copolymeric nanocarrier for the co-delivery of navitoclax and decitabine (NAV/DCB NPs) for combination cancer therapy. NAV/DCB NPs exhibited potent in vitro synergistic cytotoxicity in both acute myeloid leukemia and breast cancer cell lines.
View Article and Find Full Text PDFProgression and metastasis of ER breast cancer depend on multiple signaling cascades. The available conventional treatment options have limited efficacy in ER breast cancer due to overexpression of AKT, c-Myc and BCL-2 proteins. Simultaneous targeting and inhibition of these targets in ER cancer may result in effective therapeutic outcomes.
View Article and Find Full Text PDFThe disruption and overexpression of phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway in cancer results in tumor growth, metastasis, and survival. Treatment with common anthracyclines has confirmed cancer cells' dependence on PI3K pathway through overexpression of AKT. Moreover, combining HDAC inhibitor with anthracycline has shown the targeting of breast cancer stem cells.
View Article and Find Full Text PDFPirarubicin (PIRA) is a semi-synthetic anthracycline derivative that is reported to have lesser toxicity and better clinical outcomes as compared to its parental form doxorubicin (DOX). However, long term use of PIRA causes bone marrow suppression and severe cardiotoxicity to the recipients. Herein, we have developed a biodegradable polymeric nano platform consisting of amphiphilic di-block copolymer methoxy polyethylene glycol-polylactic acid and a hydrophobic penta-block copolymer polylactic acid-pluronic L-61-polylactic acid as a hybrid system to prepare PIRA (& DOX) encapsulated nanoparticles (NPs) with an aim to reduce its off targeted toxicity and enhance therapeutic efficacy for cancer therapy.
View Article and Find Full Text PDFHere, a study is reported on a simple, one-step method for the synthesis of a zirconium dioxide-reduced graphene oxide (ZrO-RGO) nanocomposite involving the reduction of graphene oxide (GO) and in situ growth of ZrO NPs using hydrazine as a reducer. This ZrO-RGO nanocomposite was functionalized with l-methionine (Meth) for immunosensor application. Morphological and structural studies clearly indicated that ZrO NPs (6 nm) were decorated onto the RGO sheets, and enhanced exfoliation, thereby preventing the restacking of the RGO sheets.
View Article and Find Full Text PDFIn this paper, we present the result of studies related to the in situ synthesis of amino acid (L-Cysteine) capped lanthanum hydroxide nanoparticles [Cys-La(OH) NPs] towards the fabrication of efficient immunosensor for non-invasive detection of oral cancer. The characterization of Cys-La(OH) NPs was carried out by different techniques including X-ray diffraction, scanning electron microscopy, transmission electron microscopy, fourier transform infrared spectroscopy and electrochemical techniques. These Cys-La(OH) NPs were electrophoretically deposited onto an indium-tin-oxide glass substrate and used for immobilization of anti-cytokeratin fragment-21-1 (anti-Cyfra-21-1) for the electrochemical detection of Cyfra-21-1.
View Article and Find Full Text PDFMater Sci Eng C Mater Biol Appl
January 2017
We report results of the studies relating to fabrication of an efficient immunosensor based on bismuth oxide nanorods (nBiO), electrophoretically deposited onto indium-tin-oxide (ITO) coated glass substrate. This immunosensor was fabricated by immobilization of anti-aflatoxin monoclonal antibodies (Ab-AFB1) and bovine serum albumin (BSA) for aflatoxin B1 detection. The structural and morphological studies of n-BiO have been carried out by XRD, UV-vis spectrophotometer; SEM, AFM and FTIR.
View Article and Find Full Text PDFResults of the studies are reported relating to application of the silanized nanostructured zirconia, electrophoretically deposited onto indium tin oxide (ITO) coated glass for covalent immobilization of the monoclonal antibodies (anti-CYFRA-21-1). This biosensing platform has been utilized for a simple, efficient, noninvasive, and label-free detection of oral cancer via cyclic voltammetry technique. The results of electrochemical response studies conducted on bovine serum albumin (BSA)/anti-CYFRA-21-1/3-aminopropyl triethoxy silane (APTES)/ZrO/ITO immunoelectrode reveal that this immunoelectrode can be used to measure CYFRA-21-1 (oral cancer biomarker) concentration in saliva samples, with a high sensitivity of 2.
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