Hyaluronan-Stabilized Redox-Sensitive Nanoassembly for Chemo-Gene Therapy and Dual T1/T2 MR Imaging in Drug-Resistant Breast Cancer Cells.
Santhosh Kalash RajendrakumarAkhil VenuVishnu RevuriReju George ThomasGuru Karthikeyan ThirunavukkarasuJun ZhangVeena VijayanSeok-Yong ChoiJae-Young LeeYong-Kyu LeeYong Yeon JeongIn-Kyu ParkPublished in: Molecular pharmaceutics (2019)
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 (Mn3O4) and hematite (Fe3O4) 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.
Keyphrases
- breast cancer cells
- drug resistant
- multidrug resistant
- cancer therapy
- hyaluronic acid
- photodynamic therapy
- gene therapy
- acinetobacter baumannii
- drug delivery
- clinical trial
- contrast enhanced
- gram negative
- magnetic resonance imaging
- escherichia coli
- fluorescence imaging
- iron oxide
- magnetic resonance
- crispr cas
- metabolic syndrome
- klebsiella pneumoniae
- current status
- genome wide
- type diabetes
- diffusion weighted imaging
- cell therapy
- bone marrow
- squamous cell
- radiation therapy
- gene expression
- risk assessment
- mesenchymal stem cells
- metal organic framework
- ionic liquid
- emergency department
- adverse drug
- transcription factor
- genome wide identification
- young adults
- pseudomonas aeruginosa
- dna methylation
- childhood cancer
- image quality
- human health
- double blind
- placebo controlled
- study protocol