Degradable multifunctional gold-liposomes as an all-in-one theranostic platform for image-guided radiotherapy
Graphical abstract
Section snippets
Background
Within the current landscape of oncology, radiation therapy (RT) is one of the major treatment options used today, with approximately 50 % of all patients receiving RT in some form (Baskar et al., 2012, McKelvey et al., 2018). Although RT is highly effective, it suffers from a lack of tissue selectivity, leading to numerous adverse effects in healthy tissues surrounding the tumor target. To improve tumor destruction and minimize adverse effects to healthy tissues, image-guided RT (IGRT) has
Materials
The prostate cancer cell lines PC-3 and DU-145 were purchased from American Type Culture Collection (ATCC) via Cedarlane, Burlington, ON, Canada. The Avanti Mini-Extruder, dipalmitoylphosphatidylcholine (DPPC; 25 mg/mL in chloroform), Sephadex G-50 powder, ascorbic acid, doxorubicin hydrochloride (DOX), thiazolyl blue tetrazolium bromide (MTT), iohexol, polyethylene glycol (PEG-20 k), Triton X-100, tetrachloroauric acid and methanol were purchased from Sigma Aldrich, Oakville, ON, Canada.
Synthesis and Characterization of Lipogold
To prepare Lipogold NPs, we adapted a robust method invented by Troutman et al. (Troutman et al., 2008) Using extruded pure DPPC liposomes as a template, the GNP shell was created by sequentially adding different ratios of gold chloride precursor and ascorbic acid. By varying the ratio of gold to ascorbic acid, a variety of blue-green colored nanoshells were produced, with more gold resulting in more intense and red-shifted plasmons (Fig. 2A and B). For consistency, we selected Lipogold
Discussion
Currently, one significant limitation of IGRT is a lack of viable contrast materials that can provide accurate delineation of the tumor’s margins, with large gold-based implants being the current method of choice; however, these large physical markers come with side effects such as inflammation, swelling, and bleeding that can complicate treatment prognosis. (Yin et al., 2022) Small molecule contrast agents containing iodine, while common in regular X-ray and CT imaging, have limited use in
Conclusions
In this work, our results indicate that Lipogold can be a powerful and highly customizable nanomedicine for IGRT in addition to phototherapy and chemotherapy. By combining gold and iodine for broad-spectrum CT imaging and maximizing Auger electron emission, Lipogold is an ideal platform for IGRT and its related combination strategies. While further work is needed to validate its efficacy in vivo, improve its tumor targeting, and identify the optimal formulations for encapsulating different
CRediT authorship contribution statement
Brian Youden: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing, Visualization. Feng Wang: Methodology. Xiaohan Zhang: Methodology, Investigation. Dennis Curry: Methodology, Investigation. Nicholas Majtenyi: Formal analysis, Investigation. Amani Shaaer: Formal analysis, Investigation. Kenneth Bingham: Methodology, Investigation. Quang Nguyen: Methodology, Investigation. Leslie Bragg: Resources, Writing – review &
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by the Canada Research Chairs program, the NSERC Discovery Development Program, and Canada’s Telus Ride for Dad (RFD) and The Prostate Cancer Fight Foundation (PCFF).
References (69)
- et al.
Radiosensitization by Gold Nanoparticles: Will They Ever Make It to the Clinic?
Radiother. Oncol.
(2017) - et al.
Microfluidic Encapsulation Method to Produce Stable Liposomes Containing Iohexol
J. Drug Deliv. Sci. Technol.
(2019) - et al.
Influence of Poly(Ethylene Glycol) Grafting Density and Polymer Length on Liposomes: Relating Plasma Circulation Lifetimes to Protein Binding
Biochim. Biophys. Acta - Biomembr.
(2007) - et al.
Effect of Lamellarity and Size on Calorimetric Phase Transitions in Single Component Phosphatidylcholine Vesicles
Biochim. Biophys. Acta - Biomembr.
(2015) - et al.
Iohexol Assay for Direct Determination of Glomerular Filtration Rate: Optimization and Development of an HPLC-UV Method for Measurement in Serum and Urine
Clin. Chim. Acta
(2020) - et al.
Recent Biomedical Applications of Gold Nanoparticles: A Review
Talanta
(2018) - et al.
Gold Nanoparticle-Coated Thermosensitive Liposomes for the Triggered Release of Doxorubicin, and Photothermal Therapy Using a near-Infrared Laser
Colloids Surfaces A Physicochem. Eng. Asp.
(2021) - et al.
Doxorubicin Physical State in Solution and inside Liposomes Loaded via a PH Gradient
Biochim. Biophys. Acta - Biomembr.
(1998) - et al.
Plasmonic Gold Nanoparticles: Optical Manipulation, Imaging, Drug Delivery and Therapy
J. Control. Release
(2019) - et al.
NIR Triggered Liposome Gold Nanoparticles Entrapping Curcumin as in Situ Adjuvant for Photothermal Treatment of Skin Cancer
Int. J. Biol. Macromol.
(2018)
Pitfalls of the MTT Assay: Direct and off-Target Effects of Inhibitors Can Result in over/Underestimation of Cell Viability
Gene
Pitfalls of Assays Devoted to Evaluation of Oxidative Stress Induced by Inorganic Nanoparticles
Talanta
Update on the Renal Toxicity of Iodinated Contrast Drugs Used in Clinical Medicine
Drug. Healthc. Patient Saf.
Gold Nanoparticles (GNPs) in Biomedical and Clinical Applications: A Review
Nano Sel.
Cancer and Radiation Therapy: Current Advances and Future Directions
Int. J. Med. Sci.
Improved Sensitivity of Computed Tomography towards Iodine and Gold Nanoparticle Contrast Agents via Iterative Reconstruction Methods
Sci. Rep.
Gold Nanoparticle Mediated Radiation Response among Key Cell Components of the Tumour Microenvironment for the Advancement of Cancer Nanotechnology
Sci. Rep.
Radiosensitization by Gold Nanoparticles: Effective at Megavoltage Energies and Potential Role of Oxidative Stress
Transl. Cancer Res.
Nanomedicine 2.0
Acc. Chem. Res.
CT and CEST MRI Bimodal Imaging of the Intratumoral Distribution of Iodinated Liposomes
Quant. Imaging Med. Surg.
Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy
Int. J. Nanomedicine
Antibody-Labeled Liposomes for CT Imaging of Atherosclerotic Plaques. In Vitro Investigation of an Anti-ICAM Antibody-Labeled Liposome Containing Iohexol for Molecular Imaging of Atherosclerotic Plaques via Computed Tomography
Texas Hear. Inst. J.
Protein Corona: Dr. Jekyll and Mr. Hyde of Nanomedicine
Biotechnol. Appl. Biochem.
Enhanced Immunocompatibility of Ligand-Targeted Liposomes by Attenuating Natural IgM Absorption
Nat. Commun.
Small, Long Blood Half-Life Iodine Nanoparticle for Vascular and Tumor Imaging
Sci. Rep.
Spectrally Tunable Leakage-Free Gold Nanocontainers
J. Am. Chem. Soc.
Near-Infrared Activated Release of Doxorubicin from Plasmon Resonant Liposomes
Nanotheranostics
Biocorona-Induced Modifications in Engineered Nanomaterial-Cellular Interactions Impacting Biomedical Applications
WIREs Nanomedicine and Nanobiotechnology
Liposomes Coloaded with Iopamidol/Lipiodol as a RES-Targeted Contrast Agent for Computed Tomography Imaging
Pharm. Res.
Gold Nanoparticles in Radiotherapy and Recent Progress in Nanobrachytherapy
Adv. Healthc. Mater.
Wavelength-Selective Light-Induced Release from Plasmon Resonant Liposomes
Adv. Funct. Mater.
NIR-Activated Content Release from Plasmon Resonant Liposomes for Probing Single-Cell Responses
ACS Nano
Cited by (1)
Liposomes for Cancer Theranostics
2023, Pharmaceutics