Cyclometalated Ir(III) theranostic molecular probe enabled mitochondria targeted fluorescence-SERS-guided phototherapy in breast cancer cells.

The increased energy demands inherent in cancer cells necessitate a dependence on mitochondrial assistance for their proliferation and metastatic activity. Herein, an innovative photo-medical approach has been attempted, specifically targeting mitochondria, the cellular powerhouses, to attain therapeutic benefit. This strategy facilitates the rapid and precise initiation of apoptosis, the programmed cell death process. In this goal, we have synthesized cyclometalated Iridium (III) molecular probes, denoted as Ir-CN and Ir-H, with a nitrile (CN) and a hydrogen-functionalized bipyridine as ancillary ligands, respectively. Ir-CN has shown superior photosensitizing properties and lower dark cytotoxicity compared to Ir-H in the breast cancer cell line MCF-7, positioning it as the preferred probe for photodynamic therapy (PDT). The synthesized Ir-CN induces alterations in mitochondrial membrane potential, disrupting the respiratory chain function, and generating reactive oxygen species that activate signaling pathways leading to cell death. The CN-conjugated bipyridine ligand in Ir-CN contributes to the intense red fluorescence and the positive charge on the central metal atom facilitates specific mitochondrial colocalization (colocalization coefficient of 0.90). Together with this, the Iridium metal, with strong spin-orbit coupling, efficiently generates singlet oxygen with a quantum yield of 0.79. Consequently, the cytotoxic singlet oxygen produced by Ir-CN upon laser exposure disrupts mitochondrial processes, arresting the electron transport chain and energy production, ultimately leading to programmed cell death. This mitochondrial imbalance and apoptotic induction were dually confirmed through various apoptotic assays including Annexin V staining and by mapping the molecular level changes through surface-enhanced Raman spectroscopy (SERS). Therefore, cyclometalated Ir-CN emerges as a promising molecular probe for cancer theranostics, inducing laser-assisted mitochondrial damage, as tracked through bimodal fluorescence and SERS.

Nanotheranostic Probe Built on Methylene Blue Loaded Cucurbituril [8] and Gold Nanorod: Targeted Phototherapy in Combination with SERS Imaging on Breast Cancer Cells.

Recent advancements in a nanoarchitecture platform for safe and effective targeted phototherapy in a synergistic fashion is an absolute necessity in localized cancer therapy. Photothermal and photodynamic therapies (PTT and PDT) are considered as the most promising localized therapeutic intervention for cancer management as they have no long-term side effects and are minimally invasive and affordable. Herein, we have demonstrated a tailor-made nanotheranostic probe in which macrocyclic host cucurbituril [8] (CB[8]) is placed as a glue between two gold nanorods (GNRs) within ∼3 nm gaps in linear nanoassemblies with exquisitely sensitive plasmonics that exert combined phototherapy to investigate the therapeutic progression on human breast cancer cells. Photosensitizer methylene blue was positioned on CB[8] to impart the PDT effect, whereas GNR was responsible for PTT on a single laser trigger ensuring the synchronized phototherapy. Furthermore, the nanoconstruct was tagged with targeting anti-Her2 monoclonal antibody (MB-CB[8]@GNR-anti-Her2) for localized PTT and PDT on Her2 positive SKBR3 cells, subsequent cellular recognition by surface-enhanced Raman spectroscopy (SERS) platform, and further assessment of the combined intracellular phototherapy. Hence, the current strategy is definitely marked as a proof-of-concept straightforward approach that implies the perfect nature of the combined phototherapy to achieve an efficient cancer treatment.

Antiproliferative labdane diterpenes from the rhizomes of Hedychium flavescens Carey ex Roscoe.

Antiproliferative activity was confirmed in the various extracts of rhizomes of Hedychium flavescens (Zingiberaceae). The phytochemical investigation of the rhizomes of Hedychium flavescens led to the isolation of four labdane diterpenes. Their structures were established as coronarin E (1), C-14 epimers of isocoronarin D (2), C-15 epimers of coronarin D methyl ether (3) and isocoronarin D (4). The structure of the compounds was identified based on spectroscopic analysis and on comparison with literature reports. All these compounds were assessed for their in vitro cytotoxicity against human lung adenocarcinoma (A549) cell line and showed significant cytotoxicity as reflected in IC50 value, that is, 0.52, 0.59, 0.68 and 1.22 µM compared with the control doxorubicin (IC50 0.92 µM). Moreover, all the compounds were nontoxic towards the normal lung fibroblast (WI-38) cells. The chemo-profiling and cytotoxicity study of Hedychium flavescens is reported for the first time.

Elucidating Gold-MnO2 Core-Shell Nanoenvelope for Real Time SERS-Guided Photothermal Therapy on Pancreatic Cancer Cells.

Pancreatic cancer represents one of the most aggressive in nature with a miserable prognosis that warrants efficient diagnostic and therapeutic interventions. Herein, a MnO2 overlaid gold nanoparticle (AuNPs) based photothermal theranostic nanoenvelope (PTTNe:MnO2@AuNPs) was fabricated to substantiate surface-enhanced Raman spectroscopy (SERS) guided real-time monitoring of photothermal therapy (PTT) in pancreatic cancer cells. A sharp enhancement of the fingerprint Raman signature of MnO2 at 569 cm-1 exhibited as a marker peak for the first time to elucidate the intracellular PTT event. In this strategic design, the leftover bare AuNPs after the degradation of the MnO2 layer from the nanoenvelope in the presence of intracellular H2O2 enabled real-time tracking of biomolecular changes of Raman spectral variations during PTT. Moreover, the surface of the as-synthesized nanoenvelope was functionalized with a pancreatic cancer cell targeting peptide sequence for cholecystokinin fashioned the PTTNe with admirable stability and biocompatibility. Finally, the precise cell death mechanism was explicitly assessed by SERS spectral analysis as a complementary technique. This targeted phototheranostic approach demonstrated in pancreatic cancer cells presented a therapeutically viable prototype for futuristic personalized cancer nanomedicine.