Theranostic pH-sensitive nanoparticles for highly efficient targeted delivery of doxorubicin for breast tumor treatment

Abstract

A multifunctional theranostic nanoplatform integrated with environmental responses has been developed rapidly over the past few years as a novel treatment strategy for several solid tumors. We synthesized pH-sensitive poly(β-thiopropionate) nanoparticles with a supermagnetic core and folic acid (FA) conjugation (FA-doxorubicin-iron oxide nanoparticles [FA-DOX@ IONPs]) to deliver an antineoplastic drug, DOX, for the treatment of folate receptor (FR)-overexpressed breast cancer. In addition to an imaging function, the nanoparticles can release their payloads in response to an environment of pH 5, such as the acidic environment found in tumors. After chemical ( 1 H nuclear magnetic resonance) and physical (morphology and super-magnetic) characterization, FA-DOX@IONPs were shown to demonstrate pH-dependent drug release profiles. Western blotting analysis revealed the expression of FRs in three breast cancer cell lines, MCF-7, BT549, and MD-MBA-231. The cell counting kit-8 assay and transmission electron microscopy showed that FA-DOX@IONPs had the strongest cytotoxicity against breast cancer cells, compared with free DOX and non-FR targeted nanoparticles (DOX@IONPs), and caused cellular apoptosis. The FA-DOX@IONP-mediated cellular uptake and intracellular internalization were clarified by fluorescence microscopy. FA-DOX@IONPs plus magnetic field treatment suppressed in vivo tumor growth in mice to a greater extent than either treatment alone; furthermore, the nanoparticles exerted no toxicity against healthy organs. Magnetic resonance imaging was successfully applied to monitor the nanoparticle accumulation. Our results suggest that theranostic pH-sensitive nanoparticles with dual targeting could enhance the available therapies for cancer.

Iron Oxide Nanoparticles for Biomedical Applications: A Perspective on Synthesis, Drugs, Antimicrobial Activity, and Toxicity

“…Over the last two years, the main anticancer drug coupled to IONPs was doxorubicin (DOX) [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 ]. This drug can be covalently bound to functionalized IONPs [ 123 ] or establish electrostatic interactions with negatively charged groups present in the magnetic nanocarriers [ 133 ].…”

<p>Lipid nanobubbles as an ultrasound-triggered artesunate delivery system for imaging-guided, tumor-targeted chemotherapy</p>

“…In recent years, breast cancer has attracted increasing attention due to its high morbidity and mortality in women 1,2. As breast cancer presents with high proliferation, invasion, and metastasis, affected patients have low disease-free survival and overall survival rates 3.…”

“…As breast cancer presents with high proliferation, invasion, and metastasis, affected patients have low disease-free survival and overall survival rates 3. Traditional therapeutic methods for breast cancer include surgery, chemotherapy, radiation, and hormonal therapy 1. Among these, chemotherapy is widely used and generally accepted by the patients.…”

Combined chemo-magnetic field-photothermal breast cancer therapy based on porous magnetite nanospheres

“…On the other hand, some limitations in targeted drug delivery 13 result in severe toxicity to liver, kidney and spleen [13][14][15] , as well as the poor distribution of anti-cancer drugs in tumor site 6,16 . Therefore, several strategies like development of some NP-based platforms for targeted drug delivery have been reported 4,17,18 .…”