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Targeted treatment of cancer with new dexterous strategies using biocompatible materials is the hallmark of recent cancer research. In this study three innovative designs of targeted delivery systems with hybrid materials have been developed. Two nanosilica based passive systems are developed using stimuli specific to the tumour micro environment for the delivery of anticancer drugs. In zinc oxide based, active targeted system, the technique of receptor mediation through cancer cell membrane for its internalization has been adopted. The first system is hybrid material with nanosilica based bio-responsive drug delivery system. This system has been developed through a facile surface modification of the silica nanoparticles with biocompatible material. It showed higher entrapment efficiency for anticancer drug doxorubicin with sustained drug release behaviour in vitro. Unique feature of surface charge swapping in response to the lower pH of the tumour microenvironment significantly increased the cellular internalization of the nanocarriers into the tumour tissue as compared to other vital organs. The increased uptake and controlled release of anticancer drug co-jointly contributed to suppress the tumour growth in squamous cell carcinoma (SCC7) bearing nude mice. The second nanosilica based passive targeted system focused to target the hypoxic conditions of tumour. Surface modification of the nanoparticles with biocompatible moieties made the system nontoxic for biomedical applications These PEGylated hypoxia responsive nanocarriers contained higher amount of the anticancer drug and showed sustained release of the drug in hypoxic environment with no premature release in physiological or normoxic conditions. The third system is active targeted carrier possessing core material of zinc oxide functionalized with hyaluronic acid as targeting moiety. The system showed significantly improved cellular uptake, due to receptor mediated endocytosis in T-cells, with controlled release of anticancer drug. Doxorubicin loaded nanocarriers along with methyl aminolevulinate (m-ALA) showed increased cancer cell destruction in RD cells. The biocompatibility, drug loading and its release characteristics, cell uptake, intra cellular drug release, and antitumor efficacy have been evaluated for the above systems. The obtained results exhibited the success of the carriers for their biological response. These newly designed targeted delivery systems fabricated with hybrid materials possess strong potential to open new horizons in of controlled and site specific delivery of anticancer drugs with increased bioavailability and improved therapeutic efficacy
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