Functionalized Nanomaterials as Tailored Theranostic Agents in Brain Imaging

Functionalized nanomaterials of various categories are essential for developing cancer nano-theranostics for brain diseases; however, some limitations exist in their effectiveness and clinical translation, such as toxicity, limited tumor penetration, and inability to cross blood–brain and blood-tumor barriers. Metal nanomaterials with functional fluorescent tags possess unique properties in improving their functional properties, including surface plasmon resonance (SPR), superparamagnetism, and photo/bioluminescence, which facilitates imaging applications in addition to their deliveries. Moreover, these multifunctional nanomaterials could be synthesized through various chemical modifications on their physical surfaces via attaching targeting peptides, fluorophores, and quantum dots (QD), which could improve the application of these nanomaterials by facilitating theranostic modalities. In addition to their inherent CT (Computed Tomography), MRI (Magnetic Resonance Imaging), PAI (Photo-acoustic imaging), and X-ray contrast imaging, various multifunctional nanoparticles with imaging probes serve as brain-targeted imaging candidates in several imaging modalities. The primary criteria of these functional nanomaterials for translational application to the brain must be zero toxicity. Moreover, the beneficial aspects of nano-theranostics of nanoparticles are their multifunctional systems proportioned towards personalized disease management via comprising diagnostic and therapeutic abilities in a single biodegradable nanomaterial. This review highlights the emerging aspects of engineered nanomaterials to reach and deliver therapeutics to the brain and how to improve this by adopting the imaging modalities for theranostic applications

Advances in Engineered Polymer Nanoparticle Tracking Platforms towards Cancer Immunotherapy—Current Status and Future Perspectives

Engineering polymeric nanoparticles for their shape, size, surface chemistry, and functionalization using various targeting molecules has shown improved biomedical applications for nanoparticles. Polymeric nanoparticles have created tremendous therapeutic platforms, particularly applications related to chemo- and immunotherapies in cancer. Recently advancements in immunotherapies have broadened this field in immunology and biomedical engineering, where “immunoengineering” creates solutions to target translational science. In this regard, the nanoengineering field has offered the various techniques necessary to manufacture and assemble multifunctional polymeric nanomaterial systems. These include nanoparticles functionalized using antibodies, small molecule ligands, targeted peptides, proteins, and other novel agents that trigger and encourage biological systems to accept the engineered materials as immune enhancers or as vaccines to elevate therapeutic functions. Strategies to engineer polymeric nanoparticles with therapeutic and targeting molecules can provide solutions for developing immune vaccines via maintaining the receptor storage in T- and B cells. Furthermore, cancer immunotherapy using polymeric nanomaterials can serve as a gold standard approach for treating primary and metastasized tumors. The current status of the limited availability of immuno-therapeutic drugs highlights the importance of polymeric nanomaterial platforms to improve the outcomes via delivering anticancer agents at localized sites, thereby enhancing the host immune response in cancer therapy. This review mainly focuses on the potential scientific enhancements and recent developments in cancer immunotherapies by explicitly discussing the role of polymeric nanocarriers as nano-vaccines. We also briefly discuss the role of multifunctional nanomaterials for their therapeutic impacts on translational clinical applications

Methods of Protein Detection in Cancer for Diagnosis, Prognosis and Therapy

Emerging proteomic technologies offer new insight in the study of malignant tumor to identify protein biomarkers for early detection, stratification, prediction and monitoring of treatment, as well as to detect target molecules for therapy. The tumor protein biomarker is responsible for the regulation of the cell cycle to promote cell proliferation and resistance to cell death. Important technologies include ELISA, immunohistochemistry, flow cytometry, western blot, mass spectrometry, protein microarray, and microfluidics for the study of screening, protein profiling, identification, qualitative and quantitative analysis of differential expressed oncoproteins relative to cancer tissues, counterparts at different stages of the disease from preneoplasia to neoplasia. It can also provide a detailed description of identifying tissue-specific protein biomarkers and to analysis the modification of protein activity in cancer conditions. In this chapter, we discuss current and emerging protein assays for improving cancer diagnosis, including trends toward advances in assay miniaturization, improve sensitivity and specificity, time and cost-effective, and accuracy in detection and measurement of protein activity. However, information from these protein diagnostic technologies should be integrated to obtain the optimal information required for the clinical management of a patient

Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing

The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented with other features including non-toxicity, biocompatibility, and safety

Leprosy-associated chronic wound management using biomaterials

Background: Deformities and neuropathic chronic ulcers are the common features associated with leprosy-cured individuals that impact their quality of life and impair rehabilitation efforts. The challenging aspects for treatment of chronic wounds are the factors that inhibit healing. We reasoned that limited success of various therapeutic interventions could be due to the fact that leprosy-cured individual's physiology gets acclimatized to having a chronic wound that any therapeutic intervention is counterbalanced to maintain status quo at the wound site. Therefore, an alternative strategy would be to use biomaterials that gradually alter the wound site allowing the individual's physiology to participate in the healing process. Aims: Developing the human amnion (Amn)-derived biomaterial scaffolds and evaluating its use to heal chronic wounds in leprosy-cured but deformed persons (LCDPs). Materials and Methods: Using an enzymatic protocol, we have developed a rapid method to generate biomaterial scaffolds from discarded human Amn. A clinical trial on 26 LCDPs was performed with the biomaterial, and its wound-healing potential was then compared with LCDPs undergoing standard treatment procedure. Results: Biomaterial-based treatment of chronic wounds on LCDP displayed a higher efficiency in healing when compared to standard treatment. Conclusions: This study exemplifies that biomaterial-based treatment of leprosy-wounds offers an excellent affordable alternative for wound management. This study underlines the importance of involving both local wound environment and systemic effects for healing. In addition, we highlight wound healing as a necessity for successful rehabilitation and reintegration of leprosy-cured person into the society

Multifunctional HER2-Antibody Conjugated Polymeric Nanocarrier-Based Drug Delivery System for Multi-Drug-Resistant Breast Cancer Therapy

Nanotechnology-based medical approaches have made tremendous potential for enhancing the treatment efficacy with minimal doses of chemotherapeutic drugs against cancer. In this study, using tamoxifen (Tam), biodegradable antibody conjugated polymeric nanoparticles (NPs) was developed to achieve targeted delivery as well as sustained release of the drug against breast cancer cells. Poly­(d,l-lactic-<i>co</i>-glycolic acid) (PLGA) NPs were stabilized by coating with poly­(vinyl alcohol) (PVA), and copolymer polyvinyl-pyrrolidone (PVP) was used to conjugate herceptin (antibody) with PLGA NPs for promoting the site-specific intracellular delivery of Tam against HER2 receptor overexpressed breast cancer (MCF-7) cells. The Tam-loaded PVP–PLGA NPs and herceptin-conjugated Tam-loaded PVP–PLGA NPs were characterized in terms of morphology, size, surface charge, and structural chemistry by dynamic light scattering (DLS), Transmission electron microscopy (TEM), ζ potential analysis, ¹H nuclear magnetic resonance (NMR), and Fourier transform infrared (FT-IR) spectroscopy. pH-based drug release property and the anticancer activity (in vitro and in vivo models) of the herceptin conjugated polymeric NPs were evaluated by flow cytometry and confocal image analysis. Besides, the extent of cellular uptake of drug via HER2 receptor-mediated endocytosis by herceptin-conjugated Tam-loaded PVP–PLGA NPs was examined. Furthermore, the possible signaling pathway of apoptotic induction in MCF-7 cells was explored by Western blotting, and it was demonstrated that drug-loaded PLGA NPs were capable of inducing apoptosis in a caspase-dependent manner. Hence, this nanocarrier drug delivery system (DDS) not only actively targets a multidrug-resistance (MDR) associated phenotype (HER2 receptor overexpression) but also improves therapeutic efficiency by enhancing the cancer cell targeted delivery and sustained release of therapeutic agents

HER2 Targeted Breast Cancer Therapy with Switchable “Off/On” Multifunctional “Smart” Magnetic Polymer Core–Shell Nanocomposites

Multifunctional magnetic polymer nanocombinations are gaining importance in cancer nanotheranostics due to their safety and their potential in delivering targeted functions. Herein, we report a novel multifunctional core–shell magnetic polymer therapeutic nanocomposites (NCs) exhibiting pH dependent “Off–On” release of drug against breast cancer cells. The NCs are intact in blood circulation (“Off” state), i.e., at physiological pH, whereas activated (“On” state) at intracellular acidic pH environment of the targeted breast cancer cells. The NCs are prepared by coating the cannonball (iron nanocore) with hydrophobic nanopockets of pH-responsive poly­(d,l-lactic-<i>co</i>-glycolic acid) (PLGA) polymer nanoshell that allows efficient loading of therapeutics. Further, the nanocore–polymer shell is stabilized by poly­(vinylpyrrolidone) (PVP) and functionalized with a targeting HER2 ligand. The prepared Her–Fe₃O₄@PLGA–PVP nanocomposites facilitate packing of anticancer drug (Tamoxifen) without premature release in the bloodstream, recognizing the target cells through binding of Herceptin antibody to HER2, a cell surface receptor expressed by breast cancer cells to promote HER2 receptor mediated endocytosis and finally releasing the drug at the intracellular site of tumor cells (“On” state) to induce apoptosis. The therapeutic efficiency of hemo/cytocompatible NCs drug delivery system (DDS) in terms of targeted delivery and sustained release of therapeutic agent against breast cancer cells was substantiated by <i>in vitro</i> and <i>in vivo</i> studies. The multifunctional properties of Her–Tam–Fe₃O₄@PLGA–PVP NCs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy

Induction of ROS-Dependent Mitochondria-Mediated Intrinsic Apoptosis in MDA-MB-231 Cells by Glycoprotein from Codium decorticatum

Marine macroalgae consist of a range of bioactive molecules exhibiting different biological activities, and many of these properties are attributed to sulfated polysaccharides, fucoxanthin, phycobiliproteins, and halogenated compounds. In this study, a glycoprotein (GLP) with a molecular mass of ∼48 kDa was extracted and purified from Codium decorticatum and investigated for its cytotoxic properties against human MDA-MB-231 breast cancer cells. The IC₅₀ values of GLP against MDA-MB-231 and normal breast HBL-100 cells (control) were 75 ± 0.23 μg/mL (IC₂₅), 55 ± 0.32 μg/mL (IC₅₀), and 30 ± 0.43 μg/mL (IC₇₅) and 90 ± 0.57 μg/mL (IC₂₅), 80 ± 0.48 μg/mL (IC₅₀), and 60 ± 0.26 μg/mL (IC₇₅), respectively. Chromatin condensation and poly­(ADP-ribose) polymerase (PARP) cleavage studies showed that the GLP inhibited cell viability by inducing apoptosis in MDA-MB-231 cells. Induction of mitochondria-mediated intrinsic apoptotic pathway by GLP was evidenced by the events of loss of mitochondrial membrane potential (ΔΨ_m), bax/bcl-2 dysregulation, cytochrome <i>c</i> release, and activation of caspases 3 and 9. Apoptosis-associated factors such as reactive oxygen species (ROS) formation and loss of ΔΨ_m were evaluated by DCFH-DA staining and flow cytometry, respectively. Cell cycle arrest of G₂/M phase and expression of apoptosis associated proteins were determined using flow cytometry and Western blotting, respectively