Polyethylene glycol modified ORMOSIL theranostic nanoparticles for triggered doxorubicin release and deep drug delivery into ovarian cancer spheroids
Graphical Abstract
Section snippets
Background
Theranostic nanomedicine has the potential to simultaneously treat (therapy) and image (diagnostics) cancer. Multifunctional nanoparticles encapsulated with imaging probes and chemotherapeutic agents can be delivered to tumors in-vivo passively via the enhanced permeation and retention (EPR) effect and to cancer cells through actively targeting cell specific receptors. For theranostic nanomedicine to be effective, the imaging agent and drug must be retained effectively by the carrier (against
Nanoparticle Synthesis
DOX-Silane (DOX-ICPTES) conjugate was prepared by reacting 5 mg DOX-HCL with 20 μl 3-(Triethoxysilyl)propylisocyanate (ICPTES)) in the presence of 2 M excess Triethylamine (TEA). Organically modified silica nanoparticles were formulated by a modification of the ternary microemulsion system reported by Paras et al. [11]. Briefly, 0.44 mg of Dioctyl sulfosuccinate sodium salt (AOT) was dissolved in 20 ml of deionized water followed by the addition of 800 μl 1-butanol resulting in a clear solution. To
Size and Zeta-potential
The physical characteristics of CDSIR820 and PEGCDSIR820 are shown in Table 1. In aqueous media, physical processes such as aggregation and swelling of organic groups on the nanoparticle surface determine the effective nanoparticle size measured by dynamic light scattering (hydrodynamic diameter). PEG layers on the nanoparticle surface swell in PBS and hence the hydrodynamic diameter of CDSIR820 increased to 58.2 ± 3.1 nm from 52.5 ± 2.5 (5.7 nm increase) after pegylation. Addition of PEG improved
Conclusion
We report a novel theranostic system of pegylated Ormosil nanoparticles encapsulated with NIR dye IR820 and DOX (PEGCDSIR820) that is capable of NIR imaging, chemotherapy and adjuvant NIR hyperthermia. Pegylated nanoparticles possess the physical properties, e.g., stability against aggregation in physiological media, size (50–60 nm) and surface charge (− 6.2 mV) for optimal cell uptake and passive targeting of tumors via the EPR effect. Exposure to NIR laser resulted in a rapid rise of temperature
Acknowledgements
The authors would like to acknowledge the contribution of Mr. Pedro Da Costa, Mr. Mathhew Chacko, Mr. Nour Ahlawad and Mr. Juan Pablo Olguin in assisting with the in-vivo bio distribution studies. We also thank the Chambers Lab and Dr. Jeremy W Chambers of Herbert Wertheim College of Medicine at FIU for the use of LiCor Imaging system.
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