Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells.

Autor: Rajendrakumar SK; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University , Chonnam National University Medical School , Gwangju 61469 , Republic of Korea., Venu A; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University , Chonnam National University Medical School , Gwangju 61469 , Republic of Korea., Revuri V; Department of Green Bio-Engineering , Korea National University of Transportation , Chungju 27469 , Republic of Korea., George Thomas R; Department of Radiology , Chonnam National University Hwasun Hospital , Hwasun , Jeollanam-Do 58128 , Republic of Korea., Thirunavukkarasu GK, Zhang J; Department of Biomedical Sciences , Chonnam National University Medical School , Hwasun , Jeollanam-Do 58128 , Republic of Korea., Vijayan V; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University , Chonnam National University Medical School , Gwangju 61469 , Republic of Korea., Choi SY; Department of Biomedical Sciences , Chonnam National University Medical School , Hwasun , Jeollanam-Do 58128 , Republic of Korea., Lee JY, Lee YK; Department of Green Bio-Engineering , Korea National University of Transportation , Chungju 27469 , Republic of Korea., Jeong YY; Department of Radiology , Chonnam National University Hwasun Hospital , Hwasun , Jeollanam-Do 58128 , Republic of Korea., Park IK; Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University , Chonnam National University Medical School , Gwangju 61469 , Republic of Korea.
Jazyk: angličtina
Zdroj: Molecular pharmaceutics [Mol Pharm] 2019 May 06; Vol. 16 (5), pp. 2226-2234. Date of Electronic Publication: 2019 Apr 15.
DOI: 10.1021/acs.molpharmaceut.9b00189
Abstrakt: Tailoring combinatorial therapies along with real-time monitoring strategies has been the major focus of overcoming multidrug resistance in cancer. However, attempting to develop a multifunctional nanoplatform in a single construct leads to compromising therapeutic outcomes. Herein, we developed a simple, theranostic nanoassembly containing a hyaluronic acid-stabilized redox-sensitive (HART) polyethylenimine polyplex composed of a doxorubicin (DOX) intercalated Bcl-2 shRNA encoded plasmid along with a green-synthesized hausmannite (Mn 3 O 4 ) and hematite (Fe 3 O 4 ) nanoparticle (GMF). The highly stable HART nanoassembly has enhanced CD44-mediated intracellular uptake along with hyaluronidase (hylase) and redox-responsive drug-gene release. With Bcl-2 gene silencing induced by the successful delivery of HART in multidrug-resistant MCF7 breast cancer cells, the synergistic cytotoxic effect of Bcl-2 silencing and DOX was achieved. In addition, the HART nanoassembly containing GMF exhibited excellent dual MRI contrast (T1/T2) by reducing artifact signals. Overall, the HART nanoassembly with its enhanced theranostic properties has the potential to improve the therapeutic efficacy in future preclinical and clinical trials.
Databáze: MEDLINE