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 of 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.
The biofunctional significance of hollow mesoporous silica nanoparticles (HMSNs) could be used as nano-reservoirs. Here in the b-sitosterol loaded into the hollow core and the cisplatin substituted with the carboxylic group of poly lactic acid (PLA)polyethylene glycol (PEG) on the pore walls of HMSNs. Subsequently, the tumour biomarker somatostatin peptide (3207-86) conjugated to Methyl polyethylene glycol 2-maleimide ethyl ether (Meo-PEG-Mal) for the selective targeting of tumour cells. The surface modified HMSNs enable the internalization of cisplatin via chlorine ion release, through the cleavage of the coordinated interaction. Further, the b sitosterol release is dependent on the discharge rate of cisplatin and the pH of the cell microenvironment. The engineered nano-drug delivery system could be used to selectively target cancer cells and deliver multimodal therapeutic schemes for the treatment of colon cancer
Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in bresat cancer cells: an improved nanomedicine strategies". now reads: "Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy".
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