Porphyrin and doxorubicin mediated nanoarchitectonics of copper clusters: a bimodal theranostics for cancer diagnosis and treatment in vitro.

Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.

A nanoarchitecture of a gold cluster conjugated gold nanorod hybrid system and its application in fluorescence imaging and plasmonic photothermal therapy.

Engineering different nanomaterials into a single functional material can impart unique properties of the parental nanoparticles, especially in the field of bio imaging and therapy. Gold nanomaterials having different sizes, shapes and dimensionalities exhibit exceptional properties apart from their non-toxicity and hence are strong candidates in the biomedical field. Designing a hybrid nanomaterial of two gold nanostructures retaining the individual properties of the parental nanomaterials is challenging. Here, we demonstrate the synthesis of a hybrid nanomaterial (GQC@GNR), comprising an extremely small gold nanocluster and a representative of the asymmetric gold nanostructure, i.e., a gold nanorod, both having their own different exclusive optical properties like tuneable emission and NIR absorption characteristics, respectively. The hybrid system is designed to retain its emission and absorption in the NIR region to use it as an agent for simultaneous imaging and therapy. The formation of GQC@GNR and its architectonics heavily depend on the synthesis route and the parameters adopted which in turn have a direct influence on its properties. The architecture and its connection to the optical properties are explained using UV-Vis absorption and photoluminescence spectroscopy, zeta potential, transmission electron microscopy, etc. DFT-based computational modelling supports architectonics as explained by the experimental findings. The formation of the gold-gold hybrid system witnessed interesting science with a strong indication that materials with desired properties can be designed by appropriately modulating the architectonics of hybrid formation. Finally, folate conjugated GQC@GNR demonstrated its efficacy for targeted imaging and photothermal therapy in HeLa cells and tumor-bearing animal models. The detailed therapeutic efficacy of GQC@GNR is also explained based on Raman spectroscopy.

Copper Nanocluster Enables Simultaneous Photodynamic and Chemo Therapy for Effective Cancer Diagnosis and Treatment in Vitro.

Metal-nanocluster-mediated cancer diagnosis and therapy has drawn considerable attention in recent years due to the unique optical and photophysical properties of metal clusters. This type of material is highly useful for the diagnosis, treatment, and further follow-up of disease. However, a single treatment modality is not sufficient for a complete cure. The use of a multi-therapeutic strategy is among the most promising methods for effective treatment, along with an early-stage diagnosis. To address the multiple therapeutic modalities in a single nanomaterial, a copper nanocluster was synthesized using glutathione, having inherent singlet oxygen generation and emission at 674 nm. A tumor-targeting agent (folic acid) and an anticancer drug (doxorubicin) was conjugated to the copper cluster for cancer diagnosis via targeted imaging and further double therapy (photodynamic and chemotherapy) in vitro. 10.5 µg (18.1 nmol) of drug conjugated copper cluster shows 56 % cell death for 30 second laser irradiation in HeLa cells. Effective cancer cell imaging and therapeutic efficacy are demonstrated in vitro.

Luminescent Gold Nanorods To Enhance the Near-Infrared Emission of a Photosensitizer for Targeted Cancer Imaging and Dual Therapy: Experimental and Theoretical Approach.

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.

An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster.

In this study, gold quantum clusters with distinct fluorescence properties were developed and their structural and physical behaviour was evaluated. The clusters were prepared by etching gold nanoparticles with glutathione. Three different Au33 clusters with emission profiles in the NIR region and one blue emitting cluster, Au8 were developed by varying the geometrical arrangement of atoms within the cluster. These clusters having sizes in the range of 0.7 to 2 nm were synthesized by choosing different reaction temperatures from 0 °C to 70 °C and pH between 1.5 and 10. In the three cases, formation of self assembled atoms within the cluster and the corresponding changes in optical properties were observed. A detailed evaluation of the number of atoms and the core-ligand ratio using MALDI-MS and a change in the binding energy as seen in the XPS study confirmed this finding. The study demonstrates that the self assembly of atoms and their arrangement is an important factor in determining the characteristics of the cluster. In this communication, we put forward a new concept where the number of atoms and their arrangement within the clusters play a crucial role in tuning their optical properties.

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.