Report
Teaser, summary, work performed and final results
Periodic Reporting for period 1 - PhotoNanoBone (Photoresponsive Smart Nanocarriers for Tetherless Regeneration of Bone Tissue)
Teaser
The main goal of this project was to design stimuli-responsive “smart†nanoplatforms for performing different actions inside living cells, both in 2D configuration (adherent cells) and 3D configuration (cell spheroids as a tissue-like model structure). Metal-organic...
Summary
The main goal of this project was to design stimuli-responsive “smart†nanoplatforms for performing different actions inside living cells, both in 2D configuration (adherent cells) and 3D configuration (cell spheroids as a tissue-like model structure). Metal-organic framework (MOF)-based nanocomposites were selected as the key nanomaterial to developed the “functional and customized†nanoplatform. This selection was based on the particular features of MOFs, in particular zeolitic imidazolate framework-8 (ZIF-8), which make them ideal candidates for bioapplications. These properties are mainly minimal cytotoxicity, intrinsic biodegradability, ultra-large surface-to-volume ratios, tunable pore size, high drug loading capacity, tunable structure and chemical composition, and potential for pre-/post-synthetic modifications for incorporating additional functionalities.
This approach would represent a major advance in the nanobiomedical field, and could be also extended to wider application areas such as therapeutic and regenerative nanomedicine, with the consequent expected positive impact on the society.
Work performed
Work performed and main results:
Two different smart nanoplatforms were designed aimed at different purposes as follows.
(1) Nanoplatform as nanocarrier for drug delivery in cells (cf. Figure 1A). A plasmonic core-shell nanocarrier comprising gold nanostars (AuNSs) coated with zeolitic imidazolate framework 8 (ZIF-8) was synthesized and loaded with a large amount of a cargo molecule (bisbenzimide as model cargo; loading capacity of ∼2.9×105 molecules per nanocarrier particle). The thermoresponsive behaviour under photostimulation (irradiation with near infrared light) of the developed smart nanocarrier (cargo-loaded AuNS@ZIF8) was successfully used for achieving the thermoplasmonic-driven release of the encapsulated active molecules inside living cells in a spatiotemporal controlled fashion.
(2) Nanoplatform as nanoreactor for intracellular catalysis (cf. Figure 1B). A catalytic core-shell nanocarrier comprising palladium nanocubes (Pd) coated with zeolitic imidazolate framework 8 (ZIF-8) was synthesized and internalized in cells for catalyzing specific transformations (uncaging reactions) of substrates (non-fluorescent molecules) to active fluorescent products. The developed nanoreactor (Pd@ZIF8 NR) could efficiently catalyze Pd-promoted uncaging reactions intracellularly in a very efficient manner and remaining highly active over time, demonstrating its superior performance in comparison with other reported Pd-based catalysts. This was because the MOF shell is able to protect the Pd core from passivation and deactivation, which is the main critical issue for this kind of catalysis inside cells. Even more important was to demonstrate that these NRs were readily incorporated into 3D tumor spheroids to produce a novel 3D catalytic spheroid model, which allowed for transforming recurrent batches of reactants.
To conclude, the work performed in this project has demonstrated the huge potential of the developed smart nanoplatforms for applications in diverse areas within the biomedical field. It is envisaged that this work will open the path to developing new bioapplications and designing similar nanoplatforms by adding different functionalities, with the ultimate goal of addressing critical issues of some nanomaterials that hampers nowadays their actual translation into clinical practice.
Explotation and dissemination of results:
Conferences and seminars
1. 256th American-Chemical-Society (ACS) conference. Oral Communication “Photothermal-driven drug-delivery nanoplatform based on plasmonic zeolitic imidazolate frameworksâ€. 2018, Boston, USA
2. Seminar at Center for Research in Biological Chemistry and Molecular Materials (CiQUS). Oral Communication “Light-triggered release of encapsulated cargo from core-shell gold nanostar/ZIF-8 nanoparticles inside living cellsâ€. 2018, Santiago de Compostela, Spain
3. VII Meeting on Nanochemistry and Nanotechnology (VII NANOUCO). Oral Communication “Aqueous stable gold nanostar/ZIF-8 nanocomposites for light triggered release of active cargo inside living cellsâ€. 2019, Córdoba, Spain
4. Biennial Meeting of the Spanish Royal Society of Chemistry (RSEQ)
Authors: C. Carrillo-Carrión, P. del Pino
Oral Communication “Aqueous stable gold nanostar/ZIF-8 nanocomposites for light triggered release of active cargo inside living cellsâ€. 2019, Donostia-San Sebastian, Spain
5. ICONAN 2019 - International Conference On Nanomedicine And Nanobiotechnology (ICONAN 2019). Oral Communication “Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light Triggered Release of Active Cargo Inside Living Cellsâ€. 2019, Munich, Germany
Publications (to date)
1. Carrillo-Carrion C., et al. Aqueous Stable Gold Nanostar/ZIFâ€8 Nanocompositesfor Lightâ€Triggered Release of Active Cargo Inside Living Cells. Angewandte Chemie International Edition, 2019, 58(21), 7078.
2. Carrillo-Carrion C.* Nanoscale metal-organic frameworks as key players in the context of drug delivery: evolution toward
Final results
The project offers two highly innovative aspects: i) the combination of nanoparticles with metal-organic frameworks for designing smart nanoplatforms; and ii) addressing the challenge of performing specific different functions (i.e. delivery of drugs at precise locations, or performing catalytic transformations) inside living cells and 3D tissue models in a spatiotemporal manner. Thus, the novelty and scientific impact of this project are very high, both in the fields of nanotechnology and biomedical field, reflecting the interdisciplinary nature of the research project.
In terms of quality, relevance and social impact, this project led to:
i) results published in premiere journals of the highest scientific standards and prestigious scientific conferences.
ii) its social impact is justified because of the focus on a problem of controlling functions inside living cells with application to advanced therapeutic strategies.
Thus, the project deals with one of the societal challenges of H2020: Health, Demographic Change and Wellbeing. The results of the projects allow progress towards the development of innovative biomedical tools for therapeutic purpose, with the consequent significant socio-economic benefits in the future.
Website & more info
More info: https://usc.es/ciqus/en/research/projects.