Amit Ranjan Maity

Carbon Nanoparticle-based Fluorescent Bioimaging Probes

Fluorescent nanoparticle-based imaging probes have advanced current labelling technology and are expected to generate new medical diagnostic tools based on their superior brightness and photostability compared with conventional molecular probes. Although significant progress has been made in fluorescent semiconductor nanocrystal-based biological labelling and imaging, the presence of heavy metals and the toxicity issues associated with heavy metals have severely limited the application potential of these nanocrystals. Here, we report a fluorescent carbon nanoparticle-based, alternative, nontoxic imaging probe that is suitable for biological staining and diagnostics. We have developed a chemical method to synthesise highly fluorescent carbon nanoparticles 1–10 nm in size; these particles exhibit size-dependent, tunable visible emission. These carbon nanoparticles have been transformed into various functionalised nanoprobes with hydrodynamic diameters of 5–15 nm and have been used as cell imaging probes.

Synthesis of nanobioconjugates with a controlled average number of biomolecules between 1 and 100 per nanoparticle and observation of multivalency dependent interaction with proteins and cells.

Multivalency of nanoparticle and associated cooperative binding with biological interface is an important aspect in the development of nanoparticle based bioimaging probes. However, the preparation of such a nanobioconjugate with a controlled number of biomolecules per nanoparticle, typically between 1 and 100, is challenging. Here we report a generalized two-step bioconjugation method to prepare nanobioconjugates with a varied average number of biomolecules between 1 to 100 per nanoparticle that can be applied to different nanoparticles and biomolecules. Following this approach we have successfully synthesized quantum dot (QD) based bioconjugates with controlled average numbers of glucose or folate and found their number-dependent interaction with proteins and cells. We propose a method for exploiting the nanoparticle multivalency effect toward various biological interactions and preparing such nanobioconjugates for best performance.

Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin–Gold Nanoparticles

Inhibition of amyloid fibrillation and clearance of amyloid fibrils/plaques are essential for the prevention and treatment of various neurodegenerative disorders involving protein aggregation. Herein, we report curcumin-functionalized gold nanoparticles (Au-curcumin) of hydrodynamic diameter 10-25 nm, which serve to inhibit amyloid fibrillation and disintegrate/dissolve amyloid fibrils. In nanoparticle form, curcumin is water-soluble and can efficiently interact with amyloid protein/peptide, offering enhanced performance in inhibiting amyloid fibrillation and dissolving amyloid fibrils. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach to combat neurodegenerative disease.

Thiol‐Directed Synthesis of Highly Fluorescent Gold Clusters and Their Conversion into Stable Imaging Nanoprobes

Fluorescent gold clusters (FGCs) with tunable emission from blue to red and quantum yields in the range of 6-17% have been synthesized by simple modification of the conditions used for the synthesis of gold nanoparticles, namely by replacing the stronger reducing agent with a controlled amount of thiol. Various functional FGCs with hydrodynamic diameters of 5-12 nm have been successfully synthesized and used as cell labels. The results of our investigations strongly indicate that FGCs composed of Au(0) are more stable imaging probes than commonly reported red/NIR-emitting FGCs with a composition of Au(0)/Au(I), as this combination rapidly transforms into nonfluorescent large clusters on exposure to light. The FGC-based nanoprobes reported herein exhibit stable fluorescence upon continuous light exposure and can be used as imaging probes with low cytotoxicity.

Glucose/galactose/dextran-functionalized quantum dots, iron oxide and doped semiconductor nanoparticles with <100 nm hydrodynamic diameter

Cyanoborohydride based mild conjugation chemistry has been exploited for the covalent linkage between the reducing end of carbohydrates and primary amine terminated nanoparticles. The conjugation method has been extended to different nanoparticles such as quantum dots (QDs), iron oxide or doped semiconductor nanoparticles and different carbohydrates like maltose, lactose or dextran. Water soluble nanoparticles with a tunable surface charge and a hydrodynamic diameter between 20–100 nm have been synthesized that are terminated with glucose, galactose or dextrans of different molecular weights. Carbohydrate functionalized nanoparticles have been successfully used as nanoprobes for glycoprotein sensing and cellular targeting/imaging applications. The results show that carbohydrate functionalization offers enhanced labeling specificity and reduces the non-specific binding of nanoparticles.

Folate and biotin based bifunctional quantum dots as fluorescent cell labels

Although nanoprobes functionalized with one type of affinity molecule are commonly used as bioimaging probes, biolabeling studies of nanoprobes functionalized with more than one type of affinity molecule remains an unexplored area of research. Here we show that the labeling specificity of a nanoprobe can be enhanced if they are functionalized with more than one type of affinity molecule. We have synthesized functional quantum dots (QDs) of 20–30 nm hydrodynamic diameter having both folate and biotin on their surface. This dual functional nanoprobe has an enhanced labeling specificity to cancer cells/tissue as compared to folate or biotin based monofunctional QDs.