Thermo-responsive Fluorescent Nanoparticles for Multimodal Imaging and Treatment of Cancers

Abstract

Theranostic systems capable of delivering imaging and therapeutic agents at a specific target are the focus of intense research efforts in drug delivery. To overcome non-degradability and toxicity concerns of conventional theranostic systems, we formulated a novel thermo-responsive fluorescent polymer (TFP) and conjugated it on the surface of iron oxide magnetic nanoparticles (MNPs) for imaging and therapeutic applications in solid tumors. Methods: TFP-MNPs were synthesized by copolymerizing poly(N-isopropylacrylamide), allylamine and a biodegradable photoluminescent polymer, and conjugating it on MNPs via a free radical polymerization reaction. Physicochemical properties of the nanoparticles were characterized using Fourier transform infrared spectroscopy, dynamic light scattering, and vibrational sample magnetometry. Nanoparticle cytocompatibility, cellular uptake and cytotoxicity were evaluated using in vitro cell assays. Finally, in vivo imaging and therapeutic efficacy studies were performed in subcutaneous tumor xenograft mouse models. Results: TFP-MNPs of ~135 nm diameter and-31 mV ζ potential maintained colloidal stability and superparamagnetic properties. The TFP shell was thermo-responsive, fluorescent, degradable, and released doxorubicin in response to temperature changes. In vitro cell studies showed that TFP-MNPs were compatible to human dermal fibroblasts and prostate epithelial cells. These nanoparticles were also taken up by prostate and skin cancer cells in a dose-dependent manner and exhibited enhanced killing of tumor cells at 41°C. Preliminary in vivo studies showed theranostic capabilities of the nanoparticles with bright fluorescence, MRI signal, and therapeutic efficacy under magnetic targeting after systemic administration in tumor bearing mice. Conclusion: These results indicate the potential of TFP-MNPs as multifunctional theranostic nanoparticles for various biological applications, including solid cancer management.

Current update on nanoplatforms as therapeutic and diagnostic tools: A review for the materials used as nanotheranostics and imaging modalities

“…Generally, NPs for imaging are classified in 4 major groups: magnetic [38] , magnetofluorescent [39] , Fluorescent [6] and radiolabeled [40] . They are being applied into various imaging modalities including optical, molecular, radiologic and nuclear medicine imaging [41] , [42] , [43] .…”

“…Nanotheranostics ( Fig. 1 ) are strategies based on carriers of submicron or nano sizes [1 , 6] . Such nanotheranostics can be obtained from polymeric nanoparticles (NPs) [7] , dendrimers [8] , liposomes [9] , carbon based nanomaterials [10] , metal or inorganic nanocarriers [11] and systems which integrate both of such categories i.e.…”

Theranostics Based on Magnetic Nanoparticles and Polymers: Intelligent Design for Efficient Diagnostics and Therapy

“…In another example, a thermo-responsive fluorescent polymer (TFP) was conjugated to the surface of iron oxide magnetic NPs for use as a degradable and non-toxic theranostic agent (Pandey et al, 2020 ). For this, poly(N-isopropylacrylamide) (PNIPAM), allylamine and a fluorescent polymer were copolymerized and conjugated to NPs via free radical polymerization to form TFP-NPs.…”

“…Normally, fluorescence imaging is performed along with MRI by using a fluorescently labeled polymer (Pandey et al, 2020 ). For example, functionalization of iron oxide NPs with the two- photons fluorescent dye labeled polymer yielded a nanoprobe capable of quantifying pancreatic Beta cell mass (BCM), an effective indicator of onset of type 2 diabetes (Xin et al, 2020 ).…”

Green Synthesis of Magnetite Nanoparticles using MyrtuscommunisL. Grown in Egypt

“…MNPs were reported to have some advantages in biocompatibility, biodegradability [1,2], and easily encapsulated [3]. MNPs are used in various application such as catalyst [4], biosensor [5,6], magnetic resonance imaging (MRI) [7,8] and targeted drug delivery [9,].…”