Development and evaluation of a multi-functional organic–inorganic nanotheranostic hybrid for pancreatic cancer therapy

• Published in: Biomedical materials (Bristol) Vol. 16; no. 5; pp. 55016 - 55029
• Main Authors: David, Karolyn Infanta, Ravikumar, T S, Sethuraman, Swaminathan, Krishnan, Uma Maheswari
• Format: Journal Article
• Language: English
• Published: England IOP Publishing 01.09.2021
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Chitosan - chemistry; chitosan nanoparticles; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Deoxycytidine - analogs & derivatives; Deoxycytidine - chemistry; Deoxycytidine - pharmacology; Gold - chemistry; Humans; hybrid contrast enhancer; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Pancreas - metabolism; pancreatic cancer; Pancreatic Neoplasms - metabolism; Theranostic Nanomedicine - methods; theranostic system; pancreatic cancer; chitosan nanoparticles; hybrid contrast enhancer; theranostic system
• ISSN: 1748-6041; 1748-605X
• DOI: 10.1088/1748-605X/ac177c

Pancreatic cancer is a highly invasive disease with low survival rates. The high death rates associated with pancreatic cancer are due to multiple factors including late stage diagnosis, multi-drug resistance, invasive nature and restricted access of the therapeutic moiety to the cancer cells due to the stroma. Smart multifunctional nanocarriers that deliver the therapeutic agent in to the cancer tissue as well as enable imaging of the tissue represent an emerging paradigm in cancer therapy. Accurate and reliable detection of cancerous lesions in pancreas is essential for designing appropriate therapeutic strategy to annihilate the highly aggressive pancreatic cancer. A combination of imaging modalities can enhance the reliability of cancer detection. In this context, we report here a hybrid iron oxide-gold nanoparticle with dual contrast enhancing ability for both magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) that is co-encapsulated with the nucleotide analogue gemcitabine in a chitosan matrix. The theranostic system displayed enhanced cytotoxicity against PanC-1 pancreatic cancer cells when compared to normal cells over 48 h due to differences in cell internalization. The iron oxide-gold hybrid enabled visualization of the theranostic nanoparticle by MRI as well as micro-CT. Further, the magnetocaloric effect of the iron oxide enabled faster release of the chemotherapeutic agent as well as augmented the cytotoxicity by inducing hyperthermia. This system holds promise for further exploration as an integrated diagnostic and therapeutic platform for pancreatic cancer.