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Realizing the importance of activation of the anticancer drug, its distribution, and for cancer management, a new theranostic probe has been developed. Endogenous H

Effective treatment of malignant melanoma requires an appropriate combination of therapeutic intervention with long-term prognosis as it often survives by monotherapies. Herein, we report a novel melanoma-targeted theranostic nanoenvelope (MTTNe: ISQ@BSA-AuNC@AuNR@DAC@DR5) which has been constructed by assembling a bovine serum albumin (BSA) stabilized gold nanocluster on a gold nanorod (BSA-AuNC@AuNR), a three-in-one theranostic modality, i.e., photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, tethered with a surface-enhanced Raman scattering (SERS) detection technique. The resultant MTTNe was coloaded with the melanoma-specific FDA approved drug dacarbazine (DAC) and a newly synthesized near-infrared (NIR) absorbing squaraine molecule ISQ that served partly as a photosensitizer and multiplex Raman reporter. Finally, a nanoenvelope was anchored with anti-DR5 monoclonal antibodies as a targeting motif for highly expressed melanoma-specific death receptors in malignant cells. Significant phototherapies of MTTNe were initiated upon an 808 nm single laser trigger which showed a synergistic effect of photothermal hyperthermia as well as singlet oxygen (

Target-specific reactive oxygen species (ROS)-based cancer treatments with high therapeutic efficacy and minimal side effects have been identified recently as a potentially effective cancer management strategy. Herein, we report the fabrication of a targeted nanotheranostic agent built on an iron oxide nanoparticle-decorated graphene-gold hybrid [plasmonic magnetic nanoprobe (PMNP)] for self-guided magnetic resonance (MR)/surface-enhanced Raman scattering imaging and photothermal therapy (PTT)/chemodynamic therapy (CDT). In the presence of glutathione, which is abundant in the tumor environment, the iron oxide nanoparticles undergo

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.

The development of multifunctional molecular diagnostic platforms for the concordant visualization and treatment of diseases with high sensitivity and resolution has recently become a crucial strategy in cancer management. Thus, engineering functional metamaterials with high therapeutic and imaging capabilities to elucidate diseases from their morphological behaviors to physiological mechanisms is an unmet need in the current scenario. Here, we report the design of a unique hybrid plasmonic nanoarchitecture for targeted multiple phototherapies of breast cancer by simultaneous real-time monitoring through fluorescence and surface-enhanced Raman scattering (SERS) techniques. The nanoframework consisted of plasmonic gold-graphene hybrids tethered with folic acid-ligated chitosan-modified photosensitizer (PpIX) to afford target-specific localized photothermal and photodynamic therapy. The hybrid vehicle also served as an excellent nanocarrier for the efficient loading and stimuli-responsive release of the chemotherapeutic drug doxorubicin (DOX) to enhance the therapeutic efficacy, thereby forming a trimodal nanomedicine against cancer. The cytotoxic effects induced by the cumulative action of the triplet therapeutic tools were visualized through both fluorescence and SERS imaging channels. Moreover, it also generated synchronized therapeutic effects resulting in the effective regression of tumor volume without propagating any toxic effects to other organs of the animals. Taken together, by virtue of strong light-matter interactions, the nanoprobe showed enhanced photoadsorption, which facilitated amplified light-reactive therapeutic and imaging efficacies along with targeted and enhanced chemotherapy, both in vitro and in vivo, which may offer promising outcomes in clinical research.

Precise control over the dynamics of nanoparticles (NPs) in a tumor microenvironment is highly warranted for the development of an efficient nanotheranostic agent. Even though inductively coupled plasma mass spectrometry can provide a quantitative assessment regarding the uptake efficiency of metal NPs, enumeration of deep tissue penetration capacity remains as a challenge. Herein, we have demonstrated an accurate tracking of the uptake efficiency and penetration phenomenon of gold nanoparticles (AuNPs: 40-50 nm) with respect to three different surface charges in monolayer (2D) cells, multicellular spheroids (3D) and in vivo tumors by surface-enhanced Raman spectroscopy (SERS). While positively charged AuNPs showed around two-fold increased internalization in monolayer cells, SERS-tag-based line scanning on multi-layered tumor spheroids illustrated almost nine-fold superior penetration capability with negatively charged AuNPs. Further, the enhanced solid tumor distribution contributed by the negatively charged AuNPs could appreciably escalate its clinical utility in cancer management.

Realizing the importance of activation of the anticancer drug, its distribution, and for cancer management, a new theranostic probe has been developed. Endogenous H2S stimulated the theranostic mol...

Comprehensive profiling of multiple protein targets plays a critical role in deeper understanding of specific disease conditions associated with high heterogeneity and complexity. Herein, we present the design and fabrication of smart programmable nanoarchitectures, which could integrate clinically relevant diagnostic modalities for the multiplexed detection of most prevalent panel of disease biomarkers present in lung cancer. The multiplex nanoprobes were prepared by attaching dual-functional Raman-active fluorogens onto spherical gold nanoparticles through a peptide linker, Phe-Lys-Cys (FKC), which is engineered with a cathepsin B (cathB) enzyme cleavage site. The presence of cathB induces the scission of FKC upon homing into the cancer cells, resulting in the release of the initially latent fluorophores with a concomitant quenching of the surface-enhanced Raman signal intensity, thereby realizing an on-off switching between the fluorescence and Raman modalities. The enzyme-triggered switchable nanoprobes were utilized for the simultaneous detection of pathologically relevant lung cancer targets by tethering with specific antibody units. The multiplex-targeted multicolor coded detection capability of the antitags was successfully developed as a valid protein screening methodology, which can address the unmet challenges in the conventional clinical scenario for the precise and early diagnosis of lung cancer.

We explored a rational design and synthesis of a Raman-active small molecular fluorescent probe (S1/Int-1) to acquire multicolor fluorescence-images based on intracellular nitric oxide (NO) in cancer cells. A new UV–vis absorption band centered at λab 510 nm for S1 was appeared in the presence of NO. Similarly, with increasing concentration of NO, the emission signal centered at 527 nm increased gradually. The probe S1 reacted with NO to form benzotriazole derivative Int-1 which showed characteristic intense Raman band centered at 1440 cm-1 for N N-. Individually, GSH and Cys reacted with Int-1 to offer a pair of new fluorophore 2 and 3 with different emission band centered at λem = 482 nm and λem = 453 nm respectively. Furthermore, the non-toxic probe S1 facilitated the monitoring of intracellular NO based dual colored imaging in the green and blue channel which intern allowed differentiating the intracellular GSH and Cys levels. Moreover, its cellular “off-on-off” response in the SERS spectral mode indicates that S1 can be a noninvasive tool to detect endogenous NO, GSH/Cys. Therefore, probe (S1/Int-1) could allow us monitoring of intracellular NO formation through dual channel fluorescence imaging with synchronous discrimination of thiols.

Herein we have stepped-up on a strategic spectroscopic modality by utilizing label free ultrasensitive surface enhanced Raman scattering (SERS) technique to generate a differential spectral fingerprint for the prediction of normal (NRML), high-grade intraepithelial lesion (HSIL) and cervical squamous cell carcinoma (CSCC) from exfoliated cell samples of cervix. Three different approaches i.e. single-cell, cell-pellet and extracted DNA from oncology clinic as confirmed by Pap test and HPV PCR were employed. Gold nanoparticles as the SERS substrate favored the increment of Raman intensity exhibited signature identity for Amide III/Nucleobases and carotenoid/glycogen respectively for establishing the empirical discrimination. Moreover, all the spectral invention was subjected to chemometrics including Support Vector Machine (SVM) which furnished an average diagnostic accuracy of 94%, 74% and 92% of the three grades. Combined SERS read-out and machine learning technique in field trial promises its potential to reduce the incidence in low resource countries.

Excellent multiplexing capability, molecular specificity, high sensitivity and the potential of resolving complex molecular level biological compositions augmented the diagnostic modality of surface-enhanced Raman scattering (SERS) in biology and medicine. While maintaining all the merits of classical Raman spectroscopy , SERS provides a more sensitive and selective detection and quantification platform. Non-invasive, chemically specific and spatially resolved analysis facilitates the exploration of SERS-based nano probes in diagnostic and theranostic applications with improved clinical outcomes compared to the currently available so called state-of-art technologies. Adequate knowledge on the mechanism and properties of SERS based nano probes are inevitable in utilizing the full potential of this modality for biomedical applications . The safety and efficiency of metal nanoparticles and Raman reporters have to be critically evaluated for the successful translation of SERS in to clinics. In this context, the present review attempts to give a comprehensive overview about the selected medical, biomedical and allied applications of SERS while highlighting recent and relevant outcomes ranging from simple detection platforms to complicated clinical applications.

Direct monitoring of apoptotic progression is a major step forward for the early assessment of therapeutic efficacy of certain treatments and the accurate evaluation of the spread of a disease. Here, the regulatory role of glutathione (GSH) is explored as a potential biomarker for tracking apoptosis. For this purpose, a near- infrared (NIR) squaraine dye is introduced that is capable of sensing GSH in a ratiometric manner by switching its emission from NIR (690 nm) to visible region (560 nm). The favorable biocompatible attributes of the probe facilitated the real-time monitoring of apoptotic process in line with the conventional apoptotic assay. Furthermore, the robust nature of the probe was utilized for the quantitative estimation of GSH during different stages of apoptosis. Through this study, an easy and reliable method of assaying apoptosis is demonstrated, which can provide valuable insights in translational clinical research.