Dr. Chun-Chin Wang @ Virtual Early Career European Microscopy Congress

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RaNT’s progress towards targeted nanoparticle delivery in cancer cells presented to the European Microscopy Congress 2020.

Another COVID casualty of RaNT’s 2020 conference calendar, the European Microscopy Congress (EMC2020) – due to be held in Copenhagen in August – was postponed until 2024.

The meeting was replaced with a virtual conference, exclusively for early career researchers in the microscopy field, and Dr. Chun-Chin (Chuck) Wang represented RaNT in a session on Life Sciences – from molecules to complex systems (Topic: Label-free life sciences imaging), this afternoon.

Read Chuck’s conference abstract below.

He spoke about his label-free imaging work, using multiple nonlinear optical microscopy techniques to visualise the distribution of gold nanoparticles within cancer cells.

This early experimental work contributes to fine-tuning the targeted delivery of our injected gold nanoclusters.

Imaging will allow RaNT to identify where in the cells the clusters are reaching (later work will identify their distribution within the body), providing data to feed back into the nanocluster design. This will be developed until a critical percentage of the injected dose arrive at their disease targets.

Label-free imaging of gold nanoparticles uptake by cancer cells and tissues using multimodal nonlinear optical microscopy

Author(s): Chun-Chin Wang, Priyanka Dey, Alexandra Vaideanu, Tanveer A. Tabish, Ryan Mellor, Jessica C. Mansfield, Andreas G. Schätzlein, Ijeoma F. Uchegbu, Nicholas Stone & Julian Moger

Gold nanoparticles (AuNPs) have shown great potential as biocompatible imaging probes which can be used as effective surface-enhanced Raman spectroscopy (SERS) substrates in various biomedical applications. Major applications include such fields as biosensing, bioimaging, surface-enhanced spectroscopies, and photothermal therapy for cancer treatment. Probing AuNPs in living systems is essential to reveal the interaction between AuNPs and biological tissues. Compared to conventional microscopy, nonlinear processes offer many advantages: the near-IR excitation extends the depth of penetration into tissues with minimal photodamage and the nonlinear signal dependence provides intrinsic 3D optical sectioning. Moreover, utilizing techniques such as transient absorption (TA) and stimulated Raman scattering (SRS) it is possible to derive label-free biochemical contrast of AuNPs and cellular structures. Visualising AuNPs without the use of extrinsic labels is vital since any chemical perturbation of the nanoparticles will modify their physical properties and hence uptake. In this study, we apply second harmonic generation (SHG), two-photon excited fluorescence (TPEF), transient absorption (TA), and stimulated Raman scattering (SRS) microscopy to perform label-free chemically specific imaging of AuNPs in cancer cells and tissues.

Multimodal imaging was carried by using ultrafast lasers and OPO to provide the pump and probe beams. Both femtosecond laser beams where chirped to picosecond pulses and spatially overlapped in the Spectral Focusing Timing and Recombination Unit (SF-TRU), which allowed us to rapidly select which Raman vibration was probed, and acquire other nonlinear optical signals. The AuNPs-dosed samples (human breast cancer cell line and murine breast tumour tissues) were mounted between two coverslips. The laser power at the sample was attenuated to below 10 mW in total.

In summary, we have demonstrated the in situ mapping of AuNPs uptake in cancer cells and cancerous tissues using multimodal nonlinear optical microscopy in a label free manner. We also showed that the combination of SHG, TPEF, TA, and SRS microscopy is an excellent imaging platform to study AuNPs and intrinsic biomolecules with submicron resolution, high detection sensitivity, and fast imaging speed. This capability offers a new tool for designing more efficient functionalised AuNPs and determining whether they are within vasculatures surrounding the tumour, pericellular, or cellular spaces.  

Acknowledgements

This research was supported by EPSRC Programme Grants “RaNT” (EP/R020965/1) and “CONTRAST facility” (EP/S009957/1).