Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression.

Autor:	Puvvada N; Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.; Department of Pharmacology, Dalhousie Medicine New Brunswick, Dalhousie University, New Brunswick, Canada., Rajput S; School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India., Kumar BNP; School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India., Sarkar S; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine; Richmond, VA 23298, USA., Konar S; Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India., Brunt KR; Department of Pharmacology, Dalhousie Medicine New Brunswick, Dalhousie University, New Brunswick, Canada., Rao RR; Department of Chemical and Life Science Engineering, Virginia Commonwealth University, Richmond, VA 23238, USA., Mazumdar A; Department of Clinical Cancer Prevention and Systems Biology, University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA., Das SK; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine; Richmond, VA 23298, USA.; VCU Institute of Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23238, USA.; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23238, USA., Basu R; Central Research Facility, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India., Fisher PB; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine; Richmond, VA 23298, USA.; VCU Institute of Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23238, USA.; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA 23238, USA., Mandal M; School of Medical Science and Technology, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India., Pathak A; Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal, 721302, India.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2015 Jul 06; Vol. 5, pp. 11760. Date of Electronic Publication: 2015 Jul 06.
DOI:	10.1038/srep11760
Abstrakt:	Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.
Databáze:	MEDLINE
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