Mini Reviews in Medicinal Chemistry - Volume 17, Issue 18, 2017

Increasing evidence suggests that stem cells, a small population of cells with unique selfrenewable and tumour regenerative capacity, are aiding tumour re-growth and multidrug resistance. Conventional therapies are highly ineffective at eliminating these cells leading to relapse of disease and formation of chemoresistance tumours. Cancer and stem cells targeted therapies that utilizes nanotherapeutics to delivery anti-cancer drugs to specific sites are continuously investigated. This review focuses on recent research using nanomedicine and targeting entities to eliminate cancer cells and cancer stem cells. Current nanotherapeutics in clinical trials along with more recent publications on targeted therapies are addressed.

Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized.

The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer.

Nanoparticles (NPs), the submicron-sized colloidal particles, have recently generated enormous interest among biomedical scientists, particularly in cancer therapy. A number of models are being used for exploring NPs safety and efficacy. Recently, cancer cell lines have explored as prominent experimental models for evaluating pharmacokinetic parameters, cell viability, cytotoxicity and drug efficacy in tumor cells. This review aims at thorough compilation of various cancer cell lines and in vivo models for evaluation of efficacy of NPs on one platform. This will provide a basis to explore and improvise pre-clinical models as a prelude to successful cancer research.

In the recent years, theranostic nanomedicine based strategies have gained much attention in the field of oncology particularly, in the development of new generation cancer diagnostic and therapeutic tools. Today, various approaches have been developed for bioactive(s) targeting to predefined pathological sites, as well as for quantification of physiological processes and visualization. Significant attempts have been made to combine therapeutic and diagnostic properties in to a single effective nanomedicine formulation. This concept, coined as “theranostics” is smart nanosystem(s), able to diagnose, bioactive(s) delivery and monitoring of therapeutic response. By combining therapeutic functionalities with molecular imaging, theranostic based strategies may be beneficial in the selection of therapy, planning of treatment, monitoring of objective response and planning of follow-up therapy based on the specific molecular characteristics of a disease. In this manuscript, we reviewed the recent development of theranostic approaches, various nanosystems as theranostic agents and applications of theranostic in cancer therapeutics and diagnostics.

Cancer is one of the most important causes of morbidity and mortality all across the world. On an average, every year approximately 238,000 new cases of brain and other central nervous system tumors are diagnosed around the world. Amongst all, tumors of brain account for nearly 85% to 90% of all primary central nervous system (CNS) tumors. Regardless of tremendous scientific efforts to develop newer diagnostic techniques and latest therapy, the management of brain cancer is still a challenge in neuro-oncology. Inadequate concentration of chemotherapeutics at the site of tumor restricts the complete destruction of malignant cells due to the presence of blood brain barrier. Besides, there is a necessity for improvement in tumor imaging for better characterization and visualization of tumor cells for surgical procedure. Nanoparticles offer the advantages upon many of these concerns i.e., diagnosis, capability to target therapeutic agents to the tumor sites and the ability of getting across the blood-brain barrier. Thus utilization of nanoparticles may lead to breakthrough in brain cancer management.

Cancer refers to an assemblage of lethal diseases characterized by abnormal growth of cells. The most celebrated adverse effects accredited to the cytotoxic class of anticancer agents are constructed owing to their inability to differentiate between the abnormally multiplying cancerous cell mass and the rapidly dividing healthy cells of the human body. Consequently, unknown targets chemotherapy for cancer play host to a multitude of adverse effects ranging from nausea, alopecia to torturous ages associated with the current treatment etiquette. Nano-pharmaceuticals constitute the advanced scale drug targeting technologies. Nanoemulsion is an important tool in the nano-technological arena designed for clinical and therapeutic application. Currently among different nano-carriers, nanoemulsions are extensively envisaged as efficient drug delivery systems for the targeted delivery of lipophilic cytotoxic antineoplastic agents. Beauties of nanoemulsion include optical clarity, biocompatibility, non-immunogenic, biodegradable, drug encapsulation, sustained and controlled release, nanometric size, large surface area, ease of preparation and thermodynamic stability. After excessive delving, the research fraternity has acknowledged nanoemulsions as proficient nanocarriers capable of effectively addressing the low bioavailability and noncompliance issues associated with the conventional anticancerous chemotherapeutic dosage forms. This review attempts to shed new light on the current status of nanoemulsion in the cancer therapeutics, and commercial field on the basis of morphology, formulation, characteristics and characterization parameters.

Today Cancer still remains a major cause of mortality and death worldwide, in humans. Chemotherapy, a key treatment strategy in cancer, has significant hurdles such as the occurrence of chemoresistance in cancer, which is inherent unresponsiveness or acquired upon exposure to chemotherapeutics. The resistance of cancer cells to an antineoplastic agent accompanied to other chemotherapeutic drugs with different structures and mechanisms of action called multi-drug resistance (MDR) plays an important role in the failure of chemo- therapeutics. MDR is primarily based on the overexpression of drug efflux pumps in the cellular membrane, which belongs to the ATP-binding cassette (ABC) superfamily of proteins, are P-gp (P-glycoprotein) and multidrug resistance-associated protein (MRP). Over the years, various strategies have been evaluated to overcome MDR, based not only on the use of MDR modulators but also on the implementation an innovative approach and advanced nanosized drug delivery systems. Nanomedicine is an emerging tool of chemotherapy that focuses on alternative drug delivery for improvement of the treatment efficacy and reducing side effects to normal tissues. This review aims to focus on the details biology, reversal strategies option with the limitation of MDR and various advantages of the present medical science nanotechnology with intracellular delivery aspects for overcoming the significant potential for improving the treatment of MDR malignancies.