Targeted Nanotheransotics: Integration of Preclinical MRI and CT in the Molecular Imaging and Therapy of Advanced Diseases.

The integration of preclinical magnetic resonance imaging (MRI) and computed tomography (CT) methods has significantly enhanced the area of therapy and imaging of targeted nanomedicine. Nanotheranostics, which make use of nanoparticles, are a significant advancement in MRI and CT imaging. In addition to giving high-resolution anatomical features and functional information simultaneously, these multifunctional agents improve contrast when used. In addition to enabling early disease detection, precise localization, and personalised therapy monitoring, they also enable early disease detection. Fusion of MRI and CT enables precise in vivo tracking of drug-loaded nanoparticles. MRI, which provides real-time monitoring of nanoparticle distribution, accumulation, and release at the cellular and tissue levels, can be used to assess the efficacy of drug delivery systems. The precise localization of nanoparticles within the body is achievable through the use of CT imaging. This technique enhances the capabilities of MRI by providing high-resolution anatomical information. CT also allows for quantitative measurements of nanoparticle concentration, which is essential for evaluating the pharmacokinetics and biodistribution of nanomedicine. In this article, we emphasize the integration of preclinical MRI and CT into molecular imaging and therapy for advanced diseases.

Redox-Sensitive Poly(lactic-co-glycolic acid) Nanoparticles of Palbociclib: Development, Ultrasound/Photoacoustic Imaging, and Smart Breast Cancer Therapy.

Breast cancer is one of the leading causes of mortality in women globally. The efficacy of breast cancer treatments, notably chemotherapy, is hampered by inadequate localized delivery of anticancer agents to the tumor site, resulting in compromised efficacy and increased systemic toxicity. In this study, we have developed redox-sensitive poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the smart delivery of palbociclib (PLB) to breast cancer. The particle size of formulated PLB@PLGA-NPs (nonredox-sensitive) and RS-PLB@PLGA-NPs (redox-sensitive) NPs were 187.1 ± 1.8 nm and 193.7 ± 1.5 nm, respectively. The zeta potentials of nonredox-sensitive and redox-sensitive NPs were +24.99 ± 2.67 mV and +9.095 ± 1.87 mV, respectively. The developed NPs were characterized for morphological and various physicochemical parameters such as SEM, TEM, XRD, DSC, TGA, XPS, etc. The % entrapment efficiency of PLB@PLGA-NPs and RS-PLB@PLGA-NPs was found to be 85.48 ± 1.29% and 87.72 ± 1.55%, respectively. RS-PLB@PLGA-NPs displayed a rapid drug release at acidic pH and a higher GSH concentration compared to PLB@PLGA-NPs. The cytotoxicity assay in MCF-7 cells suggested that PLB@PLGA-NPs and RS-PLB@PLGA-NPs were 5.24-fold and 14.53-fold higher cytotoxic compared to the free PLB, respectively. Further, the cellular uptake study demonstrated that redox-sensitive NPs had significantly higher cellular uptake compared to nonredox-sensitive NPs and free Coumarin 6 dye. Additionally, AO/EtBr assay and reactive oxygen species analysis confirmed the superior activity of RS-PLB@PLGA-NPs over PLB@PLGA-NPs and free PLB. In vivo anticancer activity in dimethyl-benz(a)anthracene-induced breast cancer rats depicted that RS-PLB@PLGA-NPs was highly effective in reducing the tumor size, hypoxic tumor, and tumor vascularity compared to PLB@PLGA-NPs and free PLB. Further, hemocompatibility study reveals that the developed NPs were nonhemolytic to human blood. Moreover, an in vivo histopathology study confirmed that both nanoparticles were safe and nontoxic to the vital organs.

AS1411 aptamer/RGD dual functionalized theranostic chitosan-PLGA nanoparticles for brain cancer treatment and imaging.

Conventional chemotherapy and poor targeted delivery in brain cancer resulting to poor treatment and develop resistance to anticancer drugs. Meanwhile, it is quite challenging to diagnose/detection of brain tumor at early stage of cancer which resulting in severity of the disease. Despite extensive research, effective treatment with real-time imaging still remains completely unavailable, yet. In this study, two brain cancer cell specific moieties i.e., AS1411 aptamer and RGD are decorated on the surface of chitosan-PLGA nanoparticles to improve targeted co-delivery of docetaxel (DTX) and upconversion nanoparticles (UCNP) for effective brain tumor therapy and real-time imaging. The nanoparticles were developed by a slightly modified emulsion/solvent evaporation method. This investigation also translates the successful synthesis of TPGS-chitosan, TPGS-RGD and TPGS-AS1411 aptamer conjugates for making PLGA nanoparticle as a potential tool of the targeted co-delivery of DTX and UCNP to the brain cancer cells. The developed nanoparticles have shown an average particle size <200 nm, spherical in shape, high encapsulation of DTX and UCNP in the core of nanoparticles, and sustained release of DTX up to 72 h in phosphate buffer saline (pH 7.4). AS1411 aptamer and RGD functionalized theranostic chitosan-PLGA nanoparticles containing DTX and UCNP (DUCPN-RGD-AS1411) have achieved greater cellular uptake, 89-fold improved cytotoxicity, enhanced cancer cell arrest even at lower drug conc., improved bioavailability with higher mean residence time of DTX in systemic circulation and brain tissues. Moreover, DUCPN-RGD-AS1411 have greatly facilitated cellular internalization and higher accumulation of UCNP in brain tissues. Additionally, DUCPN-RGD-AS1411 demonstrated a significant suppression in tumor growth in brain-tumor bearing xenograft BALB/c nude mice with no impressive sign of toxicities. DUCPN-RGD-AS1411 has great potential to be utilized as an effective and safe theranostic tool for brain cancer and other life-threatening cancer therapies.

Herbal Theranostics: Controlled, Targeted Delivery and Imaging of Herbal Molecules.

Modern medicine relies on a small number of key biologics, which can be found in nature but require further characterization and purification before they can be used. Since the herbal remedy is given through a dated and ineffective method of drug administration, its effectiveness is diminished. The novel form of medicine delivery has the potential to increase the effectiveness of herbal substances while decreasing their side effects. This is the main idea behind utilising different ways of drug delivery in herbal treatments. Several benefits arise from novel formulations of herbal compounds as compared to their conventional counterparts. These include enhanced penetrating ability into tissues, constant delivery of effective doses, and resistance to physical and chemical degradation. Controlled and targeted delivery that include herbal components allow for more traditional dosing while simultaneously increasing their efficacy. Enhancing the biodistribution and target site accumulation of systemically administered herbal medicines is the goal of nanomedicine formulations. The field of nanotheranostics has made significant advancements in the development of herbal compounds by combining diagnostic and therapeutic functions on a single nanoscale platform. It is critically important to create a theranostic nanoplatform that is derived from plants and is intrinsically "all-in-one" for single molecules. In addition to examining the mechanistic approach to nanoparticle synthesis, this review highlights the therapeutic effects of nanoscale phytochemical delivery systems. Furthermore, we have evaluated the scope for future advancements in this field, discussed several nanoparticles that have been developed recently for herbal imaging, and provided experimental evidence that supports their usage.

Comparative evaluation of liquid-liquid extraction and nanosorbent extraction for HPLC-PDA analysis of cabazitaxel from rat plasma.

A precise, sensitive, accurate, and validated reverse-phase high-performance liquid chromatography (RP-HPLC) method with a bioanalytical approach was utilized to analyze Cabazitaxel (CBZ) in rat plasma. Comparative research on extraction recoveries was performed between traditional liquid-liquid extraction (LLE) and synthesized graphene oxide (GO) based magnetic solid phase extraction (GO@MSPE). The superparamagnetic hybrid nanosorbent was synthesized using the combination of iron oxide and GO and subsequently applied for extraction and bioanalytical quantification of CBZ from plasma by (HPLC-PDA) analysis. Fourier- transform infrared spectroscopy (FT-IR), particle size, scanning electron microscopy (SEM), and x-ray diffraction (XRD) analysis were employed in the characterization of synthesized GO@MSPE nanosorbent. The investigation was accomplished using a shim pack C18 column (150 mm×4.6 mm, 5 µm) with a binary gradient mobile phase consisting of formic acid: acetonitrile: water (0.1:75:25, v/v/v) at a 0.8 mL/min flow rate, and a λmax of 229 nm. The limits of detection (LOD) and quantitation (LOQ) have been determined to be 50 and 100 ng/mL for both LLE and SPE techniques. The linearity range of the approach encompassed from 100 to 5000 ng/mL and was found to be linear (coefficient of determination > 0.99) for CBZ. The proposed method showed extraction recovery of 76.8-88.4% for the synthesized GO@MSPE and 69.3-77.4% for LLE, suggesting that the proposed bioanalytical approach was robust and qualified for all validation parameters within the acceptable criteria. Furthermore, the developed hybrid GO@MSPE nanosorbent with the help of the proposed RP-HPLC method, showed a significant potential for the extraction of CBZ in bioanalysis.

PTSA-induced synthesis, in silico and nano study of novel ethylquinolin-thiazolo-triazole in cervical cancer.

Aim: p-Toluenesulfonic acid-(PTSA) and grinding-induced novel synthesis of ethylquinolin-thiazolo-triazole derivatives was performed using green chemistry. Materials & methods: Development of a nanoconjugate drug-delivery system of ethylquinolin-thiazolo-triazole was carried out with D-α-tocopheryl polyethylene glycol succinate (TPGS) and the formulation was further characterized by transmission electron microscopy, atomic force microscopy, dynamic light scattering and in vitro drug release assay. The effect of 3a nanoparticles was assessed against a cervical cancer cell line (HeLa) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect on apoptosis was determined. Results & discussion: The 3a nanoparticles triggered the apoptotic mode of cell death after increasing the intracellular reactive oxygen level by enhancing cellular uptake of micelles. Furthermore, in silico studies revealed higher absorption, distribution, metabolism, elimination and toxicity properties and bioavailability of the enzyme tyrosine protein kinase. Conclusion: The 3a nanoparticles enhanced the therapeutic potential and have higher potential for targeted drug delivery against cervical cancer.

Chitosan nanoplatform for the co-delivery of palbociclib and ultra-small magnesium nanoclusters: dual receptor targeting, therapy and imaging.

Theranostic nanoparticles have gained significant attention in cancer diagnosis and therapy. In this study, estrone (ES) and folic acid (FA) functionalized single and dual receptor targeted theranostic chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were loaded with palbociclib (PB) and ultra-small magnesium nanoclusters (UMN). The developed nontargeted theranostic NPs (PB-UMN-CS-NPs), estrogen receptor targeted theranostic NPs (PB-UMN-CS-ES-NPs), folate receptor targeted theranostic NPs (PB-UMN-CS-FA-NPs), and dual targeted theranostic NPs (PB-UMN-CS-ES-FA-NPs) have particle sizes of 178.4 ± 1.21 nm, 181.6± 1.35 nm, 185.1± 1.33 nm, and 198.2± 1.43 nm with surface charges of +19.02± 0.382 mV, +13.89±0.410 mV, +16.72±0.527 mV and +15.23±0.377 mV, respectively. Cytotoxicity studies on estrogen receptor (ER) and folate receptor (FR) expressing breast cancer cells revealed that dual-targeted theranostic NPs (PB-UMN-CS-FA-ES-NPs) were more effective, inhibiting cell growth by 54.17 and 42.23 times in MCF-7 and T-47D cells compared to free PB, respectively. Additionally, developed NPs were capable of inhibiting the cell cycle progression of MCF-7 cells from the G1 phase to the S phase more efficiently compared to free PB. Ultrasound and photoacoustic (USG/PA) imaging demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs. Moreover, in vivo optical imaging demonstrated tumor specific accumulation of the dual-targeted theranostic NPs. Furthermore, in vitro hemocompatibility and histopathological studies confirmed the biocompatibility of developed nanoformulations.

Cetuximab decorated redox sensitive D-alpha-tocopheryl- polyethyleneglycol-1000-succinate based nanoparticles for cabazitaxel delivery: Formulation, lung targeting and enhanced anti-cancer effects.

This research work aims to fabricate cetuximab (CTX) decorated cabazitaxel (CBZ) loaded redox-sensitive D-alpha-tocopheryl-polyethyleneglycol-1000-succinate (TPGS-SS) nanoparticles (NPs) for epidermal growth factor receptor (EGFR)-targeted lung tumor therapy.The NPs were prepared using a dialysis bag diffusion method to produce, non-redox sensitive non targeted (TPGS-CBZ-NPs), redox-sensitive nontargeted (TPGS-SS-CBZ-NPs), and targeted redox-sensitive NPs (CTX-TPGS-SS-CBZ-NPs). Developed NPs were characterized for particle sizes, polydispersity, surface charge, surface morphologies, and entrapment efficiency. Moreover, additional in vitro studies have been conducted, including in vitro drug release, cytotoxicity, and cellular uptake studies.The particle size and charge over the surface were found to be in the range of 145.6 to 308.06 nm and -15 to -23 mV respectively. The IC50 values of CBZ clinical injection (Jevtana®), TPGS-CBZ-NPs, TPGS-SS-CBZ-NPs, and CTX-TPGS-SS-NPs were found to be 17.54 ± 3.58, 12.8 ± 2.45, 9.28 ± 1.13 and 4.013 ± 1.05 µg/ml, suggesting the 1.37, 1.89 and 4.37-folds respectively, enhancement of cytotoxicity as compared to CBZ clinical injection, demonstrating a significant augmentation in cytotoxicity. In addition, the in-vitro cellular uptake investigation showed that CTX-TPGS-SS-CMN6-NPs accumulated significantly compared to pure CMN6, TPGS-CMN6-NPs, and TPGS-SS-CMN6-NPs in the A549 cells. Furthermore, the targeting efficiency of developed NPs were analysed by ultrasound/photoacoustic and IVIS imaging.

Nanofibers of N,N,N-trimethyl chitosan capped bimetallic nanoparticles: Preparation, characterization, wound dressing and in vivo treatment of MDR microbial infection and tracking by optical and photoacoustic imaging.

Recent advancements in wound care have led to the development of interactive wound dressings utilizing nanotechnology, aimed at enhancing healing and combating bacterial infections while adhering to established protocols. Our novel wound dressings consist of N,N,N-trimethyl chitosan capped gold­silver nanoparticles (Au-Ag-TMC-NPs), with a mean size of 108.3 ± 8.4 nm and a zeta potential of +54.4 ± 1.8 mV. These optimized nanoparticles exhibit potent antibacterial and antifungal properties, with minimum inhibitory concentrations ranging from 0.390 µg ml-1 to 3.125 µg ml-1 and also exhibited promising zones of inhibition against multi-drug resistant strains of S. aureus, E. coli, P. aeruginosa, and C. albicans. Microbial transmission electron microscopy reveals substantial damage to cell walls and DNA condensation post-treatment. Furthermore, the nanoparticles demonstrate remarkable inhibition of microbial efflux pumps and are non-hemolytic in human blood. Incorporated into polyvinyl alcohol/chitosan nanofibers, they form Au-Ag-TMC-NPs-NFs with diameters of 100-350 nm, facilitating efficient antimicrobial wound dressing. In vivo studies on MDR microbial-infected wounds in mice showed 99.34 % wound healing rate within 12 days, corroborated by analyses of wound marker protein expression levels and advanced imaging techniques such as ultrasound/photoacoustic imaging, providing real-time visualization and blood flow assessment for a comprehensive understanding of the dynamic wound healing processes.

Nanoparticles for Thrombus Diagnosis and Therapy: Emerging Trends in Thrombus-theranostics.

Cardiovascular disease is one of the chief factors that cause ischemic stroke, myocardial infarction, and venous thromboembolism. The elements that speed up thrombosis include nutritional consumption, physical activity, and oxidative stress. Even though the precise etiology and pathophysiology remain difficult topics that primarily rely on traditional medicine. The diagnosis and management of thrombosis are being developed using discrete non-invasive and non-surgical approaches. One of the emerging promising approach is ultrasound and photoacoustic imaging. The advancement of nanomedicines offers concentrated therapy and diagnosis, imparting efficacy and fewer side effects which is more significant than conventional medicine. This study addresses the potential of nanomedicines as theranostic agents for the treatment of thrombosis. In this article, we describe the factors that lead to thrombosis and its consequences, as well as summarize the findings of studies on thrombus formation in preclinical and clinical models and also provide insights on nanoparticles for thrombus imaging and therapy.

Nattokinase Encapsulated Nanomedicine for Targeted Thrombolysis: Development, Improved in Vivo Thrombolytic Effects, and Ultrasound/Photoacoustic Imaging.

Nattokinase (NK), a potent thrombolytic enzyme that dissolves blood clots, is highly used in the treatment of cardiovascular disorders. However, its effective delivery remains demanding because of stability and bioavailability problems owing to its high molecular weight and proteineous nature. In this research, we have developed novel NK-loaded nontargeted liposomes (NK-LS) and targeted liposomes (RGD-NK-LS and AM-NK-LS) by the reverse phase evaporation method. The physiochemical characterizations (particle size, polydispersity index, zeta potential, and morphology) were performed by a Zetasizer, SEM, TEM, and AFM. The Bradford assay and XPS analysis confirmed the successful surface conjugation of the targeting ligands. Platelet interaction studies by CLSM, photon imager optima, and flow cytometry showed significantly higher (P < 0.05) platelet binding affinity of targeted liposomes. In vitro evaluations were performed using human blood and a fibrinolysis study by CLSM imaging demonstrating the potent antithrombotic efficacy of AM-NK-LS. Furthermore, bleeding and clotting time studies revealed that the targeted liposomes were free from any bleeding complications. Moreover, the in vivo FeCl3 model on Sprague-Dawley (SD) rats using a Doppler flow meter and ultrasound/photoacoustic imaging indicated the increased % thrombolysis and potent affinity of targeted liposomes toward the thrombus site. Additionally, in vitro hemocompatibility and histopathology studies demonstrated the safety and biocompatibility of the nanoformulations.

Nanotheranostics: Molecular Diagnostics and Nanotherapeutic Evaluation by Photoacoustic/Ultrasound Imaging in Small Animals.

Nanotheranostics is a rapidly developing field that integrates nanotechnology, diagnostics, and therapy to provide novel methods for imaging and treating wide categories of diseases. Targeted nanotheranostics offers a platform for the precise delivery of theranostic agents, and their therapeutic outcomes are monitored in real-time. Presently, in vivo magnetic resonance imaging, fluorescence imaging, ultrasound imaging, and photoacoustic imaging (PAI), etc. are noninvasive imaging techniques that are preclinically available for the imaging and tracking of therapeutic outcomes in small animals. Additionally, preclinical imaging is essential for drug development, phenotyping, and understanding disease stage progression and its associated mechanisms. Small animal ultrasound imaging is a rapidly developing imaging technique for theranostics applications due to its merits of being nonionizing, real-time, portable, and able to penetrate deep tissues. Recently, different types of ultrasound contrast agents have been explored, such as microbubbles, echogenic exosomes, gas-vesicles, and nanoparticles-based contrast agents. Moreover, an optical image obtained through photoacoustic imaging is a noninvasive imaging technique that creates ultrasonic waves when pulsed laser light is used to expose an object and creates a picture of the tissue's distribution of light energy absorption on the object. Contrast agents for photoacoustic imaging may be endogenous (hemoglobin, melanin, and DNA/RNA) or exogenous (dyes and nanomaterials-based contrast agents). The integration of nanotheranostics with photoacoustic and ultrasound imaging allows simultaneous imaging and treatment of diseases in small animals, which provides essential information about the drug response and the disease progression. In this review, we have covered various endogenous and exogenous contrast agents for ultrasound and photoacoustic imaging. Additionally, we have discussed various drug delivery systems integrated with contrast agents for theranostic application. Further, we have briefly discussed the current challenges associated with ultrasound and photoacoustic imaging.

EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel: Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging.

In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 µg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.

Dual-targeted transferrin and AS1411 aptamer conjugated micelles for improved therapeutic efficacy and imaging of brain cancer.

Brain tumors represent an aggressive form of cancer, posing significant challenges in achieving complete remission. Development of advanced therapies is crucial for improving clinical outcomes in cancer patients. This study aimed to create a novel treatment approach using dual-targeted transferrin (TF) and AS1411 conjugated micelles, designed to enhance therapeutic effectiveness of docetaxel (DTX) and facilitate gadolinium (Gd) based imaging in brain cancer. Micelles were prepared using a slightly modified solvent-casting method, and the dual-targeting ligands were attached to the micelle's surface through a physical adsorption process. Average particle size of micelles ranged from 117.49 ± 3.90-170.38 ± 3.39 nm, with a low polydispersity index. Zeta potential ranged from - 1.5 ± 0.02 to - 18.7 ± 0.04 mV. Encapsulation efficiency of DTX in micelles varied from 92.64 ± 4.22-79.77 ± 4.13 %. Simultaneously, encapsulation of Gd in micelles was found to be 48.27 ± 3.18-58.52 ± 3.17, respectively. In-vitro drug release studies showed a biphasic sustained release profile, with DTX and Gd release continuing up to 72 h with their t50 % at 4.95, 11.29, and 24.14 h for GDTP, GDTP-TF and GDTP-TF-AS1411 micelles, respectively. Cytotoxicity effect of GDTP-TF-AS1411 micelles has shown significant improvement (P < 0.001) and reduced IC50 value up to 0.19 ± 0.14 µg/ml compared to Taxotere® (2.73 ± 0.73 µg/ml). Theranostic study revealed higher accumulation of GDTP-TF and GDTP-TF-AS1411 micelles free GD treated animal brains. The AUC of GDTP-TF-AS1411 micelles exhibited 23.79 ± 17.82 µg.h/ml higher than Taxotere® (14.14 ± 10.59 µg.h/ml). These findings direct enhanced effectiveness in brain cancer therapy leading to improved therapeutics in brain cancer patients. The combined targeted ligands and therapeutic agents strategy can direct advancement in brain cancer therapy and offer improved therapy for patients.

Current Advances in Nanotheranostics for Molecular Imaging and Therapy of Cardiovascular Disorders.

Cardiovascular diseases (CVDs) refer to a collection of conditions characterized by abnormalities in the cardiovascular system. They are a global problem and one of the leading causes of mortality and disability. Nanotheranostics implies to the combination of diagnostic and therapeutic capabilities inside a single nanoscale platform that has allowed for significant advancement in cardiovascular diagnosis and therapy. These advancements are being developed to improve imaging capabilities, introduce personalized therapies, and boost cardiovascular disease patient treatment outcomes. Significant progress has been achieved in the integration of imaging and therapeutic capabilities within nanocarriers. In the case of cardiovascular disease, nanoparticles provide targeted delivery of therapeutics, genetic material, photothermal, and imaging agents. Directing and monitoring the movement of these therapeutic nanoparticles may be done with pinpoint accuracy by using imaging modalities such as cardiovascular magnetic resonance (CMR), computed tomography (CT), positron emission tomography (PET), photoacoustic/ultrasound, and fluorescence imaging. Recently, there has been an increasing demand of noninvasive for multimodal nanotheranostic platforms. In these platforms, various imaging technologies such as optical and magnetic resonance are integrated into a single nanoparticle. This platform helps in acquiring more accurate descriptions of cardiovascular diseases and provides clues for accurate diagnosis. Advances in surface functionalization methods have strengthened the potential application of nanotheranostics in cardiovascular diagnosis and therapy. In this Review, we have covered the potential impact of nanomedicine on CVDs. Additionally, we have discussed the recently developed various nanoparticles for CVDs imaging. Moreover, advancements in the CMR, CT, PET, ultrasound, and photoacoustic imaging for the CVDs have been discussed. We have limited our discussion to nanomaterials based clinical trials for CVDs and their patents.

Chitosan-g-estrone Nanoparticles of Palbociclib Vanished Hypoxic Breast Tumor after Targeted Delivery: Development and Ultrasound/Photoacoustic Imaging.

Breast cancer is the leading cause of death among women globally. Approximately 80% of all breast cancers diagnosed are overexpressed with estrogen receptors (ERs). In this study, we have developed an estrone (Egen)-grafted chitosan-based polymeric nanocarrier for the targeted delivery of palbociclib (PLB) to breast cancer. The nanoparticles (NPs) were prepared by solvent evaporation using the ionic gelation method and characterized for particle size, zeta potential, polydispersity, surface morphology, surface chemistry, drug entrapment efficiency, cytotoxicity assay, cellular uptake, and apoptosis study. The developed PLB-CS NPs and PLB-CS-g-Egen NPs had a particle size of 116.3 ± 1.53 nm and 141.6 ± 1.97 nm, respectively. The zeta potential of PLB-CS NPs and PLB-CS-g-Egen NPs was found to be 18.70 ± 0.416 mV and 12.45 ± 0.574 mV, respectively. The morphological analysis demonstrated that all NPs were spherical in shape and had a smooth surface. An in vitro cytotoxicity assay was performed in estrogen receptor (ER)-expressing MCF7 cells and T47D cells, which suggested that targeted NPs were 57.34- and 30.32-fold more cytotoxic compared to the pure PLB, respectively. Additionally, cell cycle analysis confirmed that cell cycle progression from the G1 into S phase was blocked more efficiently by targeted NPs compared to nontargeted NPs and PLB in MCF7 cells. In vivo pharmacokinetic studies demonstrated that entrapment of the PLB in the NPs improved the half-life and bioavailability by ∼2-3-fold. Further, ultrasound and photoacoustic imaging of DMBA induced breast cancer in the Sprague-Dawley (SD) rat showed that targeted NPs completely vanished breast tumor, reduced hypoxic tumor volume, and suppressed tumor angiogenesis more efficiently compared to the nontargeted NPs and free PLB. Further, in vitro hemocompatibility and histopathology studies suggested that NPs were biocompatible and safe for clinical use.

EGFR targeted albumin nanoparticles of oleanolic acid: In silico screening of nanocarrier, cytotoxicity and pharmacokinetics for lung cancer therapy.

This study aimed to develop cetuximab (CTX) functionalized albumin nanoparticles (ALB-NPs) of oleanolic acid for EGFR targeted lung cancer therapy. The molecular docking methodology has been applied for a selection of suitable nanocarrier. Various physicochemical parameters like particle size, polydispersity, zeta potential, morphology, entrapment efficiency, and in-vitro drug release of all the ALB-NPs were analyzed. Furthermore, the in-vitro qualitative and quantitative cellular uptake study revealed that higher uptake of CTX conjugated ALB-NPs than nontargeted ALB-NPs in A549 cells. The in-vitro MTT assay revealed that the IC50 value of CTX-OLA-ALB-NPs (4.34 ± 1.90 µg/mL) was significantly reduced (p < 0.001) than OLA-ALB-NPs (13.87 ± 1.28 µg/mL) in A-549 cells. CTX-OLA-ALB-NPs caused apoptosis in A-549 cells at concentrations equivalent to its IC50 value and blocked the cell cycle in the G0/G1 phases. The hemocompatibility, histopathology and lung safety study confirmed the biocompatibility of the developed NPs. In vivo ultrasound and photoacoustic imaging confirmed the targeted delivery of the NPs to lung cancer. The findings demonstrated that CTX-OLA-ALB-NPs have potential for site-specific delivery of OLA for effective and targeted therapy of lung carcinoma.

Theranostics of metal-organic frameworks: image-guided nanomedicine for clinical translation.

Metal-organic frameworks (MOFs)-based theranostic nanomedicine has demonstrated enormous potential for cancer diagnosis and therapy due to its versatile physiochemical properties, such as structural and morphological properties, specific cellular targeting, tunable pore and particle size, higher surface area, drug-loading capacity, biodegradability and biocompatibility. Notably, MOFs, loaded with diagnostic and therapeutic agents and functionalized with targeting moiety, are capable of catering to both targeted imaging and therapy simultaneously. Additionally, MOFs have demonstrated excellent potential in drug delivery, drug targeting, bioimaging, biosensing, biocatalysis and so on. However, major challenges associated with MOFs include improving their stability, biocompatibility and therapeutic efficacy and reducing the toxicity. This special report sheds light on the historical development, synthesis, recent advancements, toxicity and challenges associated with MOFs-based cancer nanotheranostics for their clinical translation.

Subthreshold Doses of Inflammatory Mediators potentiate one another to Elicit Reflex Cardiorespiratory Responses in Anesthetized Rats.

BACKGROUND: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intra-arterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work. OBJECTIVE: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats. METHODS: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 µM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 µM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control. RESULTS: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [P <0.01, two-sided Dunnett's test] but not in saline pretreated groups [P >0.05, two-sided Dunnett's test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykinin-pretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [P <0.05, two-sided Dunnett's test]. CONCLUSION: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.