Lakshmi V. Nair

Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters

Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 μg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

Quantum dot tailored to single wall carbon nanotubes: a multifunctional hybrid nanoconstruct for cellular imaging and targeted photothermal therapy.

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells.

Perspective: Exchange reactions in thiolate-protected metal clusters

Thiolate-protected metal clusters can exchange ligands or metal atoms with other substances such as coexisting ligands, complexes, and metal clusters in solution. Using these reactions, it is possible to synthesize metal clusters with new physical and chemical properties. Although the occurrence of such reactions was recognized nearly 20 years ago, their details were not well understood. In recent years, techniques for the precise synthesis of metal clusters and their characterization have progressed considerably and, as a result, details of these reactions have been clarified. In this perspective, we focus on the most-studied thiolate-protected gold clusters and provide a summary of recent findings as well as future expectations concerning the exchange reactions of these clusters.

Blood brain barrier permeable gold nanocluster for targeted brain imaging and therapy: an in vitro and in vivo study.

Blood brain barrier (BBB) is a dynamic interface, comprising polarized endothelial cells, that separates the brain from the circulatory system. The highly protective nature of this tight junction impairs diagnosis and treatment of brain disorders. In this study, we designed a sub atomic size, near infrared emitting, dual function glutathione gold cluster with high fluorescence yield to facilitate permeability of BBB, for imaging applications and drug delivery. The gold cluster was then modified with Levodopa (l-dopa), to utilize the large amino acid transporter 1 (LAT1) pathways to enhance brain entry. Uptake and permeability of the nanoprobes were demonstrated using an established model of BBB, comprising brain endothelial cells (bEnd.3). The uptake and the clearance of l-dopa modified cluster was faster than the glutathione cluster. l-Dopa modified cluster supports the slow and sustained delivery of a model drug, pilocarpine, to the brain. Results of in vivo imaging and drug release in normal mice hold promise for considering the probe for early diagnosis of brain diseases, when the barrier is not disrupted, and for subsequent drug treatment.

Thiolate-Protected Trimetallic Au∼20Ag∼4Pd and Au∼20Ag∼4Pt Alloy Clusters with Controlled Chemical Composition and Metal Positions

The mixing of heteroelements in metal clusters is a powerful approach to generate new physical/chemical properties and functions. However, as the kinds of elements increase, control of the chemical composition and geometric structure becomes difficult. We succeeded in the compositionally selective synthesis of phenylethanethiolate-protected trimetallic Au∼20Ag∼4Pd and Au∼20Ag∼4Pt clusters, Au∼20Ag∼4Pd(SC2H4Ph)18 and Au∼20Ag∼4Pt(SC2H4Ph)18. Single-crystal X-ray structural analysis revealed the precise position of each metal element in these metal clusters. Reacting with thiol at an elevated temperature was found to be important to direct the metal elements to the most stable positions. The electronic structures of these trimetallic clusters become more discretized than those of the related bimetallic clusters due to orbital splitting.

Atomic and Isomeric Separation of Thiolate-Protected Alloy Clusters

Techniques to control the chemical compositions and geometric structures of alloy clusters are indispensable to understand the correlation between the structures and physical/chemical properties of alloy clusters. In this study, we established a method to separate thiolate-protected 25-atom gold-silver alloy clusters (Au25- xAg x(SR)18) according to their chemical composition and structural isomer. Furthermore, using this method, we revealed that an isomeric distribution of the products exists in Au25- xAg x(SR)18 ( x ≥ 2) and that the distribution of these isomers depends on the synthesis method and standing time in solution. In this study, it was also demonstrated that the continuous discretization of the electronic structure is induced by the Ag substitution. This method can also be used to separate mixtures of [Au24M(SR)18]0 (M = Au, Pt, or Pd) and other Au-Ag alloy clusters ([Au36- xAg x(SR)24]0 and [Au38- xAg x(SR)24]0). This method is expected to be used to obtain comprehensive knowledge of the structural-property correlation of alloy clusters.