In recent years, various nanomaterial-based drug delivery nanoplatforms have been widely developed in preclinical studies for the potential targeted cancer chemotherapy. However, the advanced microscopic study for better optimization of physicochemical properties of these drug delivery nanoplatforms is not well studied so far which limits their successes in clinical applications. Therefore, superior understandings of the interaction of nanocarrier with different physicochemical properties with biological systems are essential and challenging for improved cancer treatments. In this study, we are focusing on the evaluation of different physicochemical properties such as surface functionality and degradation of periodic mesoporous organosilica nanoparticles (nanoPMOs) by super-resolution STORM technique. For this purpose, we have synthesized a library of redox-responsive antibody-conjugated biodegradable nanoPMOs with controlled size, shape, composition, orientation, and multivalency. The structural properties (i.e. size and shape) of nanoPMOs labeled with STORM-compatible dye are resolved by direct stochastic optical reconstruction microscopy (dSTORM) imaging due to higher spatial resolution compared to conventional microscopy. The degradation of functionalized nanoPMOs induced by elevated concentrations of reduced glutathione that mimic the intracellular reducing environment has been measured qualitatively and quantitatively for the first time using single-molecule localization microscopy (dSTORM). The results show that nanoPMOs properties significantly influence their degradation. To understand the role of multivalency in nanoPMOs targeting cancer cells, we have employed dSTORM imaging to evaluate the surface functionality of nanoPMOs conjugated with antibody in different orientations and multivalency. In addition to physical properties (i.e. size and shape), the surface functionality of nanoPMOs plays a significant role in their cellular uptake process. The outstanding drug loading capability into the mesoporous structure and glutathione-induced rapid drug release behaviour of selective nanoPMOs enable to produce the potent anticancer effects against prostate cancer. Thus, the nanoPMOs with optimized properties have a high potential as drug delivery nanoplatforms in targeted chemotherapy of prostate cancer.
Pradip Das obtained his B.Sc. (Hons) in 2009 and M.Sc. in 2011 in Chemistry from Vidyasagar University, India, and the Indian Institute of Technology Kharagpur, India, respectively. He received his Ph.D. in Chemistry from Indian Association for the Cultivation of Science, India (degree awarded by Jadavpur University, India) in 2016 under the supervision of Prof. Nikhil R. Jana. He completed his first postdoctoral research with Prof. Ulrich J. Krull from the University of Toronto Mississauga, Canada. Then he joined as a postdoctoral fellow at the University of Milano-Bicocca, Italy, for his second postdoctoral research with Prof. Davide Prosperi. He finished his postdoctoral research with Dr. Teresa Pellegrino at the Italian Institute of Technology Genova, Italy. Nowadays, he is working as a Marie-Curie postdoctoral fellow with Dr. Jean-Olivier Durand at the Institute Charles Gerhardt Montpellier, CNRS, France. He has published 26 papers that have been cited more than 1425 times.
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