Recent advancements of hydrogels in immunotherapy: Breast cancer treatment.

Breast cancer is the most prevalent cancer among women and the leading cause of cancer-related deaths in this population. Recent advances in Immunotherapy, or combined immunotherapy, offering a more targeted and less toxic approach, expand the survival rate of patients more than conventional treatment. Notably, hydrogels, a versatile platform provided promising avenues to combat breast cancer in preclinical studies and extended to clinical practices. With advantages such as the alternation of tumor microenvironment, immunomodulation, targeted delivery of therapeutic agents, and their sustained release at specific sites of interest, hydrogels can potentially be used for the treatment of breast cancer. This review highlights the advantages, mechanisms of action, stimuli-responsiveness properties, and recent advancements of hydrogels for treating breast cancer immunotherapy. Moreover, post-treatment and its clinical translations are discussed in this review. The integration of hydrogels in immunotherapy strategies may pave the way for more effective, personalized, and patient-friendly approaches to combat breast cancer, ultimately contributing to a brighter future for breast cancer patients.

Cell selective BCL-2 inhibition enabled by lipid nanoparticles alleviates lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease with a high mortality rate due to limited treatment options. Current therapies cannot effectively reverse the damage caused by IPF. Research suggests that promoting programmed cell death (apoptosis) in myofibroblasts, the key cells driving fibrosis, could be a promising strategy. However, inducing apoptosis in healthy cells like epithelial and endothelial cells can cause unwanted side effects. This project addresses this challenge by developing a targeted approach to induce apoptosis specifically in myofibroblasts. We designed liposomes (LPS) decorated with peptides that recognize VCAM-1, a protein highly expressed on myofibroblasts in fibrotic lungs. These VCAM1-targeted LPS encapsulate Venetoclax (VNT), a small molecule drug that inhibits BCL-2, an anti-apoptotic protein. By delivering VNT directly to myofibroblasts, we hypothesize that VCAM1-VNT-LPS can selectively induce apoptosis in these cells, leading to reduced fibrosis and improved lung function. We successfully characterized VCAM1-VNT-LPS for size, surface charge, and drug loading efficiency. Additionally, we evaluated their stability over three months at different temperatures. In vitro and in vivo studies using a bleomycin-induced mouse model of lung fibrosis demonstrated the therapeutic potential of VCAM1-VNT-LPS. These studies showed a reduction in fibrosis-associated proteins (collagen, α-SMA, VCAM1) and BCL-2, while simultaneously increasing apoptosis in myofibroblasts. These findings suggest that VCAM1-targeted delivery of BCL-2 inhibitors using liposomes presents a promising and potentially selective therapeutic approach for IPF.

Cadherin-11 targeted cell-specific liposomes enabled skin fibrosis treatment by inducing apoptosis.

Continuous and aberrant activation of myofibroblasts is the hallmark of pathological fibrosis (e.g., abnormal wound healing). The deposition of excessive extracellular matrix (ECM) components alters or increases the stiffness of tissue and primarily accounts for multiple organ dysfunctions. Among various proteins, Cadherin-11 (CDH11) has been reported to be overexpressed on myofibroblasts in fibrotic tissues. Anti-apoptotic proteins such as (B cell lymphoma-2) (BCL-2) are also upregulated on myofibroblasts. Therefore, we hypothesize that CDH11 could be a targeted domain for cell-specific drug delivery and targeted inhibition of BCL-2 to ameliorate the development of fibrosis in the skin. To prove our hypothesis, we have developed liposomes (LPS) conjugated with CDH11 neutralizing antibody (antiCDH11) to target cell surface CDH11 and loaded these LPS with a BCL-2 inhibitor, Navitoclax (NAVI), to induce apoptosis of CDH11 expressing fibroblasts. The developed LPS were evaluated for physicochemical characterization, stability, in vitro therapeutic efficacy using dermal fibroblasts, and in vivo therapeutic efficacy in bleomycin-induced skin fibrosis model in mice. The findings from in vitro and in vivo studies confirmed that selectivity of LPS was improved towards CDH11 expressing myofibroblasts, thereby improving therapeutic efficacy with no indication of adverse effects. Hence, this novel research work represents a versatile LPS strategy that exhibits promising potential for treating skin fibrosis.

Targeted Biodegradable Near-Infrared Fluorescent Nanoparticles for Colorectal Cancer Imaging.

Colorectal cancer (CRC) is the third leading cause of cancer death in the U.S., and early detection and diagnosis are essential for effective treatment. Current methods are inadequate for rapid detection of early disease, revealing flat lesions, and delineating tumor margins with accuracy and molecular specificity. Fluorescence endoscopy can generate wide field-of-view images enabling detection of CRC lesions and margins; increased signal intensity and improved signal-to-noise ratios can increase both speed and sensitivity of cancer detection. For this purpose, we developed targeted near-infrared (NIR) fluorescent silica nanoparticles (FSNs). We tuned their size to 50-200 nm and conjugated their surface with an antibody to carcinoembryonic antigen (CEA) to prepare CEA-FSNs. The physicochemical properties and biodegradable profiles of CEA-FSN were characterized, and molecular targeting was verified in culture using HT29 (CEA positive) and HCT116 (CEA negative) cells. CEA-FSNs bound to the HT29 cells to a greater extent than to the HCT116 cells, and smaller CEA-FSNs were internalized into HT29 cells more efficiently than larger CEA-FSNs. After intravenous administration of CEA-FSNs, a significantly greater signal was observed from the CEA-positive HT29 than the CEA-negative HCT116 tumors in xenografted mice. In F344-PIRC rats, polyps in the intestine were detected by white-light endoscopy, and NIR fluorescent signals were found in the excised intestinal tissue after topical application of CEA-FSNs. Immunofluorescence imaging of excised tissue sections demonstrated that the particle signals coregistered with signals for both CRC and CEA. These results indicate that CEA-FSNs have potential as a molecular imaging marker for early diagnosis of CRC.

Sustainable Alternatives to Petroleum-Derived Excipients in Pharmaceutical Oil-in-Water Creams.

Recently, vast efforts towards sustainability have been made in the pharmaceutical industry. In conventional oil-in-water (O/W) cream formulations, various petroleum-based excipients, namely mineral oil and petrolatum, are commonly used. Natural or synthetic excipients, derived from vegetable sources, were explored as alternatives to petroleum-based excipients in prototype topical creams, with 1% (w/w) lidocaine. A conventional cream comprised of petroleum-derived excipients was compared to creams containing sustainable excipients in terms of key quality and performance attributes, physicochemical properties, and formulation performance. The petrolatum-based control formulation had the highest viscosity of 248.0 Pa·s, a melting point of 42.7°C, a low separation index at 25°C of 0.031, and an IVRT flux of 52.9 µg/cm2/h. Formulation SUS-4 was the least viscous formulation at 86.9 Pa·s, had the lowest melting point of 33.6°C, the highest separation index of 0.120, and the highest IVRT flux of 139.4 µg/cm2/h. Alternatively, SUS-5 had a higher viscosity of 131.3 Pa·s, a melting point of 43.6°C, a low separation index of 0.046, and the lowest IVRT flux of 25.2 µg/cm2/h. The cumulative drug permeation after 12 h from SUS-4, SUS-5, and the control were 126.2 µg/cm2, 113.8 µg/cm2, and 108.1 µg/cm2, respectively. The composition of the oil-in-water creams had influence on physicochemical properties and drug release; however, skin permeation was not impacted. Sustainable natural or synthetic excipients in topical cream formulations were found to be suitable alternatives to petroleum-based excipients with comparable key quality attributes and performance attributes and should be considered during formulation development.

Mucoadhesive Carrier-Mediated Oral Co-delivery of Bcl2 Inhibitors Improves Gastric Cancer Treatment.

Gastric cancer treatment is challenging due to the lack of early-stage diagnostic technology and targeted delivery systems. Currently, the available treatments for gastric cancer are surgery, chemotherapy, immunotherapy, and radiation. These strategies are either invasive or require systemic delivery, exerting toxicities within healthy tissues. By creation of a targeted delivery system to the stomach, gastric cancer can be treated in the early stages. Such an approach reduces the negative effects on the rest of the body by minimizing systemic absorbance and random localization. With this in mind, we developed a mucoadhesive vehicle composed of ß-Glucan And Docosahexaenoic Acid (GADA) for controlled drug/gene delivery. In the current study, we investigated the therapeutic effect of codelivery Bcl2 inhibitors navitoclax (NAVI) and siRNA (Bcl2) via oral using GADA. The therapeutic efficacy of the GADA-mediated oral NAVI/siRNA was investigated in a gastric cancer mouse model. Higher Bcl2 inhibition efficacy was observed in Western blotting and TUNEL assay in mice treated with GADA/NAVI/siRNA compared to free NAVI, siRNA, and NAVI/siRNA. Histology (H&E) and immunohistochemistry (Ki67, TUNEL, and BCl2) analyses confirmed a significant reduction of the tumor region. Interaction between GADA and mucus resulted in retention for over 6 h and thereby sustained local payload release. The developed oral carrier GADA is an emerging vehicle that has promising potential in oral delivery of both small and large molecules, and their mucoadhesive property results in improved therapeutic efficacy with minimal side effects compared to conventional treatment. This study opens a new window for the effective delivery of oral medicine for the treatment of gastric cancer and other gastrointestinal diseases.

Carbon Coated Iron-Cobalt Nanoparticles for Magnetic Particle Imaging.

Magnetic particle imaging (MPI) is an emerging imaging modality that provides direct and quantitative mapping of iron oxide tracers. To achieve high sensitivity and good spatial resolution images, a magnetic nanoparticle with a higher contrast intensity needs to be developed. Currently, a majority of MPIs being developed for potential clinical application are composed of iron oxide nanoparticles with a spherical shape. In this project, we intend to report development of high-performance carbon (C) coated iron-cobalt (FeCo) nanoparticles (FeCo/C) and investigate their feasibility as a MPI agent. We have synthesized FeCo/C through a facile and simple method at mild temperature that is safe, easy, and up-scalable. We studied the structural and functional relationships and biocompatibility of this MPI agent in vitro. However, to enhance the aqueous solubility and biocompatibility, the surface of FeCo/C was modified with polyethylene glycol (PEG). We found that variation in the ratio of Fe and Co plays a vital role in their physical properties and functionality. In vitro imaging confirms that the Fe3Co1/C nanoparticle has highly competitive MPI intensity compared to VivoTrax, a commercially available MPI agent. Confocal laser scanning microscopy imaging with Rhodamine B labeled FeCo/C displays cellular internalization by the A375 cancer cells. The in vitro toxicity analysis concludes that there is no significant toxicity of FeCo/C nanoparticles. Therefore, the newly developed MPI agent holds strong promise for biomedical imaging and could be further validated in vivo in small animals.

A photothermal driven chemotherapy for the treatment of metastatic melanoma.

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

RGD Peptide-Functionalized Polyether Ether Ketone Surface Improves Biocompatibility and Cell Response.

Polyether ether ketone (PEEK) is a biocompatible polymer used in maxillofacial and orthopedic applications because of its mechanical properties and chemical stability. However, this biomaterial is inert and requires surface modification to make it bioactive, enhancing implant-tissue integration and giving the material the ability to interact with the surrounding microenvironment. In this paper, surface of PEEK was activated by oxygen plasma treatment and this resulted in increasing reactivity and surface hydrophilicity. Then, a polydopamine (PDA) coating was deposited over the surface followed by biofunctionalization with an RGD peptide. The plasma effect was studied by contact angle measurements and scanning electron microscopy. X-ray photoelectron spectroscopy confirmed the presence of PDA coating and RGD peptide. Crystallinity and phase identification were carried out through X-ray diffraction. Quantification of the immobilized peptide over the PEEK surface was reached through UV-vis spectroscopy. In addition, in vitro tests with fibroblast cell line (NIH/3T3) determined the viability, attachment, spreading, and proliferation of these cells over the modified PEEK surfaces. According to the results, PEEK surfaces functionalized with peptides demonstrated an increased cellular response with each successive surface modification.

Theranostic applications of multifunctional carbon nanomaterials.

Nanobiotechnology is one of the leading research areas in biomedical science, developing rapidly worldwide. Among various types of nanoparticles, carbon nanomaterials (CNMs) have attracted a great deal of attention from the scientific community, especially with respect to their prospective application in the field of disease diagnosis and therapy. The unique features of these nanomaterials, including favorable size, high surface area, and electrical, structural, optical, and chemical properties, have provided an excellent opportunity for their utilization in theranostic systems. Carbon nanotubes, carbon quantum dots, graphene, and fullerene are the most employed CNMs in biomedical fields. They have been considered safe and efficient for non-invasive diagnostic techniques such as fluorescence imaging, magnetic resonance imaging, and biosensors. Various functionalized CNMs exhibit a great capacity to improve cell targeting of anti-cancer drugs. Due to their thermal properties, they have been extensively used in cancer photothermal and photodynamic therapy assisted by laser irradiation and CNMs. CNMs also can cross the blood-brain barrier and have the potential to treat various brain disorders, for instance, neurodegenerative diseases, by removing amyloid fibrils. This review has summarized and emphasized on biomedical application of CNMs and their recent advances in diagnosis and therapy.

ß-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer.

Based on cancer-related deaths, stomach cancer is ranked fifth, and first among Hispanics. Lack of technologies for early diagnosis and unavailability of target-specific therapeutics are largely the causes of the poor therapeutic outcomes from existing chemotherapeutics. Currently available therapeutic modalities are invasive and require systemic delivery, although the cancer is localized in the stomach at its early stage. Therefore, we hypothesize that an oral local delivery approach can extend the retention duration of the therapeutics modalities within the stomach and thereby enhance therapeutic efficacy. To accomplish this, we have developed a ß-glucan (BG)-based oral delivery vehicle that can adhere to the mucus lining of the stomach for an extended period while controlling the release of Bcl2 siRNA and 5-fluorouracil (5FU) payload for over 6 h. We found that Bcl2 siRNA selectively knocked down the Bcl2 gene in a C57BL/6 stomach cancer mouse model followed by upregulation of apoptosis and remission of cancer. BG was found to be very effective in maintaining the stability of siRNA for at least 6 h, when submerged in simulated gastric juice tested in vitro. To investigate the potential therapeutic effects in vivo, we used a stomach cancer mouse model, where C57BL/6 mice were treated with 5FU, BG/5FU, siRNA, BG/siRNA, and BG/5FU/siRNA. Higher inhibition of Bcl2 and therapeutic efficacy were observed in mice treated with BG/5FU/siRNA confirmed with Western blotting and a TUNEL assay. Significant reduction in the tumor region was observed with histology (H&E) and immunohistochemistry (Ki67, TUNEL, and Bcl2) analyses. Overall, the oral formulation shows improved efficacy with nonsignificant side effects compared to the conventional treatment tested in the gastric cancer mouse model.

Oral delivery of RNAi for cancer therapy.

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.

The beneficial role of exercise in preventing doxorubicin-induced cardiotoxicity.

Doxorubicin is a highly effective chemotherapeutic agent widely used to treat a variety of cancers. However, the clinical application of doxorubicin is limited due to its adverse effects on several tissues. One of the most serious side effects of doxorubicin is cardiotoxicity, which results in life-threatening heart damage, leading to reduced cancer treatment success and survival rate. Doxorubicin-induced cardiotoxicity results from cellular toxicity, including increased oxidative stress, apoptosis, and activated proteolytic systems. Exercise training has emerged as a non-pharmacological intervention to prevent cardiotoxicity during and after chemotherapy. Exercise training stimulates numerous physiological adaptations in the heart that promote cardioprotective effects against doxorubicin-induced cardiotoxicity. Understanding the mechanisms responsible for exercise-induced cardioprotection is important to develop therapeutic approaches for cancer patients and survivors. In this report, we review the cardiotoxic effects of doxorubicin and discuss the current understanding of exercise-induced cardioprotection in hearts from doxorubicin-treated animals.

Potential and Progress of 2D Materials in Photomedicine for Cancer Treatment.

Over the last decades, photomedicine has made a significant impact and progress in treating superficial cancer. With tremendous efforts many of the technologies have entered clinical trials. Photothermal agents (PTAs) have been considered as emerging candidates for accelerating the outcome from photomedicine based cancer treatment. Besides various inorganic and organic candidates, 2D materials such as graphene, boron nitride, and molybdenum disulfide have shown significant potential for photothermal therapy (PTT). The properties such as high surface area to volume, biocompatibility, stability in physiological media, ease of synthesis and functionalization, and high photothermal conversion efficiency have made 2D nanomaterials wonderful candidates for PTT to treat cancer. The targeting or localized activation could be achieved when PTT is combined with chemotherapies, immunotherapies, or photodynamic therapy (PDT) to provide better outcomes with fewer side effects. Though significant development has been made in the field of phototherapeutic drugs, several challenges have restricted the use of PTT in clinical use and hence they have not yet been tested in large clinical trials. In this review, we attempted to discuss the progress, properties, applications, and challenges of 2D materials in the field of PTT and their application in photomedicine.

Detection of Leptin Using Electrocatalyst Mediated Impedimetric Sensing.

Obesity is a complex disorder associated with immense health consequences including high risk of cardiovascular diseases, diabetes, and cancer. Abnormality in the thyroid gland, genetics, less physical activity, uptake of excessive diet, and leptin resistance are critical factors in the development of obesity. To determine the treatment strategy, understanding the pathophysiology of obesity is crucial. For instances, leptin resistance mediated obesity defined by the presence of excessive leptin hormone (Lep) in the systemic circulation is very common in diet induced obesity. Therefore, our hypothesis is that quantitative measurement of Lep from blood can help to identify individuals with Lep resistant mediated obesity and thereby guide toward a proper treatment strategy. In this work, we aim to utilize an electrochemical immunosensing platform for diagnosis of obesity by measuring the Lep content in systemic circulation. A porous carbon confined FeNi bimetallic system was synthesized with three different ratios of Fe and Ni ions using high temperature pyrolysis technique. The suitability of the sensor for detecting Lep was studied using both CV and EIS techniques. The limit of detection (LOD) for GCE was recorded as 157.4 fg/mL with a wide linear concentration range of 500 fg/mL to 80 ng/mL, while for SPCE the LOD was 184.9 fg/mL with a linear range of 500 fg/mL to 50 ng/mL. Finally, the feasibility and applicability of the sensor for Lep detection was tested with serum collected from high fat diet induced obese rats. The selectivity, sensitivity, storage, and experimental stability and reproducibility tests showed potential for this biosensor platform as a point-of-care Lep detection device.

Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism.

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug-resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase-independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2-/- ) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.

Mucoadhesive carriers for oral drug delivery.

Among the various dosage forms, oral medicine has extensive benefits including ease of administration and patients' compliance, over injectable, suppositories, ocular and nasal. Despite of extensive demand and emerging advantages, over 50% of therapeutic molecules are not available in oral form due to their physicochemical properties. More importantly, most of the biologics, proteins, peptide, and large molecular drugs are mostly available in injectable form. Conventional oral drug delivery system has limitation such as degradation and lack of stability within stomach due to presence of highly acidic gastric fluid, hinders their therapeutic efficacy and demand more frequent and higher dosing. Hence, formulation for controlled, sustained, and targeted drug delivery, need to be designed with feasibility to target the specific region of gastrointestinal (GI) tract such as stomach, small intestine, intestine lymphatic, and colon is challenging. Among various oral delivery approaches, mucoadhesive vehicles are promising and has potential for improving oral drug retention and controlled absorption to treat local diseases within the GI tract, as well systemic diseases. This review provides the overview about the challenges and opportunities to design mucoadhesive formulation for oral delivery of therapeutics in a way to target the specific region of the GI tract. Finally, we have concluded with future perspective and potential of mucoadhesive formulations for oral local and systemic delivery.

Detection of Anticancer Drug-Induced Cardiotoxicity Using VCAM1-Targeted Nanoprobes.

Chemotherapy-induced cardiac toxicity is an undesirable yet very common effect that increases the risk of death and reduce the quality of life of individuals undergoing chemotherapy. However, no feasible methods and techniques are available to monitor and detect the degree of cardiotoxicity at an early stage. Therefore, in this project, we aim to develop a fluorescent nanoprobe to image the toxicity within the cardiac tissue induced by an anticancer drug. We have observed that vascular cell adhesion molecule 1 (VCAM1) protein alone with collagen was overly expressed within the heart, when an animal was treated with doxorubicin (DOX), because of inflammation in the epithelial cells. We hypothesize that developing a VCAM1-targeted peptide-based (VHPKQHRGGSKGC) fluorescent nanoprobe can detect and visualize the affected heart. In this regard, we prepared a poly(lactic-co-glycolic acid) (PLGA) nanoparticle linked with VCAM1 peptide and rhodamine B (PLGA-VCAM1-RhB). Selective binding and higher accumulation of the PLGA-VCAM1-RhB nanoprobes were detected in DOX-treated human cardiomyocyte cells (HCMs) compared to the untreated cells. For in vivo studies, DOX (5 mg/kg) was injected via the tail vein once in two weeks for 6 weeks (3 injection total). PLGA-VCAM1-RhB and PLGA-RhB were injected via the tail vein after 1 week of the last dose of DOX, and images were taken 4 h after administration. A higher fluorescent signal of PLGA-RhB-VCAM-1 (48.62% ± 12.79%) was observed in DOX-treated animals compared to the untreated control PLGA-RhB (10.61% ± 4.90) within the heart, indicating the specificity and targeting ability of PLGA-VCAM1-RhB to the inflamed tissues. The quantified fluorescence intensity of the homogenized cardiac tissue of PLGA-RhB-VCAM1 showed 156% higher intensity than the healthy control group. We conclude that PLGA-VCAM1-RhB has the potential to bind inflamed cardiac cells, thereby detecting DOX-induced cardiotoxicity and damaged heart at an early stage.

Ionic liquid-mediated delivery of a BCL-2 inhibitor for topical treatment of skin melanoma.

Skin melanoma is one of the most common cancer types in the United States and worldwide, and its incidence continues to grow. Primary skin melanoma can be removed surgically when feasible and if detected at an early stage. Anti-cancer drugs can be applied topically to treat skin cancer lesions and used as an adjunct to surgery to prevent the recurrence of tumor growth. We developed a topical formulation composed of Navitoclax (NAVI), a BCL-2 inhibitor that results in apoptosis, and an ionic liquid of choline octanoate (COA) to treat early-stage melanoma. NAVI is a small hydrophobic molecule that solubilizes at 20% (w/v) when dissolved in 50% COA. Although NAVI is a highly effective chemotherapeutic, it is equally thrombocytopenic. We found that COA-mediated topical delivery of NAVI enhanced its penetration into the skin and held the drug in the deeper skin layers for an extended period. Topical delivery of NAVI produced a higher cancer-cell killing efficacy than orally administrated NAVI. In vivo experiments in a mouse model of human melanoma-induced skin cancer confirmed the formulation's effectiveness via an apoptotic mechanism without any significant skin irritation or systemic absorption of NAVI. Overall, this topical approach may provide a safe and effective option for better managing skin cancer in the clinic.

Graphene: A Promising Theranostic Agent.

Graphene has drawn tremendous interest in the field of nanoscience as a superior theranostic agent owing to its high photostability, aqueous solubility, and low toxicity. This monoatomic thick building block of a carbon allotrope exhibits zero to two-dimensional characteristics with a unique size range within the nanoscale. Their high biocompatibility, quantum yield, and photoluminescent properties make them more demandable in biomedical research. Its application in biomedical sciences has been limited due to its small-scale production. Large-scale production with an easy synthesis process is urgently required to overcome the problem associated with its translational application. Despite all possible drawbacks, the graphene-based drug/gene delivery system is gaining popularity day by day. To date, various studies suggested its application as a theranostic agent for target-specific delivery of chemotherapeutics or antibiotics against various diseases like cancer, Alzheimer's diseases, multidrug resistance diseases, and more. Also, studying the toxicological profile of graphene derivatives is very important before starting its practical use in clinical applications. This chapter has tried to abbreviate several methods and their possible incoming perspective as claimed by researchers for mass production and amplifying graphene-based treatment approaches.