Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy
Chandran MuruganKathirvel RayappanRamar ThangamRamasamy BhanumathiKrishnamurthy ShanthiRaju VivekThirumurugan RamasamyAtanu BhattacharyyaSrinivasan SivasubramanianPalani GunasekaranSoundarapandian Kannan
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Abstract Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo . The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.Keywords:
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Triple-negative breast cancer
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Drugs can be delivered using oral nanocarriers in controlled, site-specific releases. Target receptors are physically, chemically, and biologically conjugated while administering a specific medicine. Since micro carriers have a 200 nm width, nanomedicine typically refers to objects with that size. Drugs can be delivered by nanocarriers to parts of the body that are inaccessible. Nanocarriers cannot deliver large pharmaceutical dosages due to their small size. Emulsion-based nanocarriers often have poor drug loading and encapsulation, which restricts their potential for therapeutic use. Various therapeutic nanocarriers exist. Ultrabright nanocarriers, polymeric nanocarriers, smart nanocarriers, nanocomposites, protein nanocarriers, nucleic acid-based nanocarriers, carbon nanotubes, and nanobubbles are examples of novel nanocarriers. All of them have successfully treated cancer. This review looks at targeted drug delivery methods and nanocarriers.
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Herein, we developed a magnetic drug delivery system based on magnetic Fe3O4 nanoparticles with double shells of modified salep polysaccharide for the delivery of doxorubicin (Dox). The drug-loaded nanocarrier was synthesized in an easy way, and large amounts of drug molecules were loaded into the nanocarrier. The drug-loaded nanocarrier showed excellent pH responsibility in vitro, and large amounts of Dox were released at lower pH (60% release), whereas the nanocarrier was stable at neutral pH. The hemolysis assay results showed that the nanocarrier has negligible hemolytic effects on human red blood cells and showed good biocompatibility. Moreover, the result of coagulation assays showed that the nanocarrier was not active in any coagulation pathways. Cytotoxicity assays of nanocarrier and drug-loaded nanocarrier toward HeLa cells demonstrated that the nanocarrier has negligible toxicity, whereas the drug-loaded nanocarrier kills more than 90% of cells during 48 h. The flow cytometry analysis also showed that the uptake of drug-loaded nanocarrier into the cancerous cells is time-dependent and higher concentrations of drug internalized into the cells at longer incubation time. On the basis of the results, we suggest that the present nanocarrier can be applicable for in vivo drug delivery as an easy-made and cheap nanocarrier.
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Recently, the development of nanotechnology and nanomaterial has promoted extremely the application of drug delivery systems in the biomedical field. However, the drug delivery into the central nervous system (CNS) is limited because the existence of the blood brain barrier (BBB). Therefore, to develop the efficient drug delivery systems (DDS) for crossing the BBB into the lesions is necessary. The holistic DDS, which successfully transfer drug into the brain, should be explored on the basis of biodegradable and non-cytotoxic nanomaterial. In this review, we discussed the applications of nanoparticles-mediated DDS in the CNS and focused on the varied nanocarrier strategies used for crossing the BBB and targeting the brain lesions, such as poly (PEG, PLA, and PLGA) covalent-attached to nanoparticles strategies, lipid nanocarrier DDS strategy, polymeric/dendritic nanocarrier DDS strategies, magnetic nanocarrier DDS strategy, and other (carbon nanotubes, viral, gold, silica etc.) nanocarrier DDS strategies. In conclusion, the platform carrying nanoparticles-based drug vehicle is vital and promising for developing the special brain drug delivery system. In future multifunctional nanocarriers may play more important role in treating various neurological diseases. Keywords: Nanoparticle, drug delivery system, central nervous system, blood brain barrier.
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Since the discovery of nanomedicine-based drug delivery carriers such as nanoparticles, liposomes, and self-nanoemulsifying drug delivery systems (SNEDDS), enormous progress has been achieved in the field of innovative active biomolecule drug delivery systems [...].
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