Current Drug Metabolism - Volume 19, Issue 9, 2018

Background: The prolonged circulation time of nanoparticles in the blood is a prerequisite to realize a controlled and targeted (passive or active targeting) release of the encapsulated gene/drug at the desired site of action. The most popular method to mask or camouflage nanoparticles is the adsorbed, grafted or conjugated of poly (ethylene glycol) (PEG) or other hydrophilic polymers (e.g. polysaccharides) to the particle surface. However, the circulation half-life of nanoparticles still cannot satisfy the need of clinical use. Method: This review focuses on several recent advances in the design and fabrication of polymeric nanoparticles with long circulating characters in blood. The factors influencing the physicochemical characteristics of nanoparticle surface and its surface modification have been discussed. Results: Gene/drug carriers can also be combined with functionalized physical, chemical or biological stimuli to improve passive and active targeting strategies. The choice of suitable manufacturing technique of polymeric nanoparticles depends on the gene/drug to be encapsulated in the particle, the physicochemical properties of the polymer, their therapeutic goal to be reached and the scalability of the fabrication which allows for a clinical realization of the most promising nanomedicines. The factors influencing long circulating properties of nanoparticles are mainly particle size, surface charge and hydrophilicity. Surface modification of polymeric nanoparticles has been focused on PEG, polysaccharides, and so on. Conclusion: Identification of novel potential coating materials with satisfied characters is an emerging field of interest in the design of long circulating polymer-based nanoparticulate gene/drug delivery.

Background: Apoptosis is one of the pathways of programmed cell death (PCD), which leads to pathognomic cellular changes different from cellular necrosis. It includes the death receptor pathway and the mitochondrial pathway, both of which involve many key proteins abnormally expressed in apoptosis-related diseases, such as cancer. The majority of anti-cancer natural products promote apoptosis to induce cancer cell death. In this review, we aim to survey the current knowledge on key apoptotic proteins and some representative natural products that can induce cancer cell apoptosis by regulating these proteins. Method: We reviewed the recent relative literatures using a structured search of bibliographic databases, and the keywords, such as natural products, cancer therapy, and apoptosis pathway, were used for inclusion/exclusion criteria. Results: One hundred and seventy-one papers are included in this review. Numerous natural products have been reported to induce cell apoptosis by regulating the expression of key apoptotic proteins, leading to a variety of antitumor effects. This review identifies the major apoptotic proteins and elaborates the interaction between the apoptotic proteins and various natural anti-cancer products. Conclusion: This review provides substantial evidences of apoptosis pathways in cancer cells and the apoptotic proteins modulated by active natural products, which may help to gain a comprehensive understanding for the development of natural drugs for better cancer treatment.

Background: For safe and effective therapy, drugs are supposed to be actively targeted at the desired disease locations. As a promising candidate for drug delivery, long circulating system with various strategies has been widely used. Recently, biomimetic strategies mediated long circulation of drug delivery system have been increasingly developed for forming various nanoparticles and shown the anticipated potential. Method: In this review, a variety of approaches for long circulation strategy have been surveyed, together with different modifications. The future perspectives as well as challenges in this field are also discussed. Results: Amounts of papers from nearly 5 years were included in the review, this review identified PEGylation, liposomal, biomimetic materials were the effective strategy for drug long circulation. Conclusion: The findings of this review confirm the importance of long circulation for drug delivery. Designing of a delivery system requires an appropriate balance between the stability of material and the long term circulation in body, which can be tailored to a specific application, based on experience optimization and customized design. Biomimetic design strategy is likely to revolutionize the current medical condition. In the medical field, using these emerging technologies on materials is promising to improving the traditional modalities and achieving novel applications on long circulation of delivery systems.

Background: Nanoparticles play an important role in the area of drug delivery and have been applied in lung cancer treatments for the purpose of controlled release and cancer cell targeting. Method: A review covering various nanoparticle formulations for lung cancer therapy is presented. The pharmacodynamic models for evaluating anti-lung cancer drugs are summarized upon drug administration routes. Moreover, the current clinical applications of nano-drugs for lung cancer treatments are also reviewed, including the administration routes, dose forms and clinical trials. Results: The preparation methods of anti-lung cancer nanoparticles varied from different formulations. Owing to the improvement of their bioavailability, stability and residency at lung, the anti-lung cancer drugs encapsulated by nanoparticles showed better therapeutic effects than the naked drug. Likewise, characterization including pharmacology, physical and chemical properties should be taken into consideration. More importantly, different pharmacological animal models should be correctly selected for the pharmacodynamics assessment. Finally, the investigation of anti-lung cancer nanoparticles in clinical trials provided experience on further related research. Conclusion: Nanoparticle delivery system for lung cancer therapy is still in its early stage and expecting numerous challenges.

Background: Nanotechnology based diagnostic and therapeutic approaches have attracted great interest in oncology over the last few years. Especially gold (Au)-based nanoformulations have gained a lot of attention in cancer detection, therapy and monitoring of outcome. The current report provides a summary of methods how to prepare different types of synthetic gold nanoformulations and their potential applications in boosting photothermal and photodynamic tumor therapies and in radiosensitization. Method: A comprehensive review of the literature on the current status of gold nanoparticles preparation methods and their application for cancer therapy was performed. Results: The intrinsic properties of the nanoparticles such as shape, size, electronic, optical, physicochemical and surface plasmon resonance (SPR) features could be precisely adjusted through various synthetic approaches depending on the further application of particles in biomedicine. According to various reports, gold nanoformulations have shown promising potential as adjuvants for photothermal and photodynamic therapies and as radiosensitizers for radiation therapy. Conclusion: Synthetic development of gold nanoformulations became an important strategy in nanomedicine. Nanocomplexes demonstrated a therapeutic potential and could be translated into clinical strategies for cancer therapy.

Background: Despite extensive advances have been made in constructing polysaccharide-based nanomedicines for target cancer therapy due to their biocompatibility, easy-functionalizability and high targeting property, there is no review concentrating the significance of the intrinsic targeting properties of polysaccharides. This review mainly focuses on the recent progress on polysaccharide-based nanoparticles which have been applied in gene delivery, drug delivery and theranostics for targeted cancer therapies. Notably, representative polysaccharides with intrinsic targeting capability used as targeting ligand are well discussed. Conclusion: It has been found that polysaccharides have become a class of promising biopolymer carrier materials to deliver anti-cancer therapeutic molecules. Among all of polysaccharides, those who are with intrinsic properties of targeting are most frequently used. Therefore, this review revealed the importance of understanding the natural functions of polysaccharides to tailor nanocarrier platforms and ultimately surmount challenges in targeted cancer therapy.

Background: Metformin is widely used for management of Type 2 Diabetes Mellitus (T2DM). Recently growing evidences have shown its anti-cancer effects. The results are mainly from observational studies and thus few information is available concerning the mechanisms of action. Method: This paper reviews recent available evidences for anti-cancer effects of metformin. The effects of metformin in specific cancers including colorectal, prostate, pancreatic, renal, cervical, endometrial, gastric, lung, breast, and ovarian cancer are reviewed. Results: Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) plays an important role in mechanism of action of metformin. The anti-cancer mechanisms of metformin include direct and indirect effects. The direct effects of metformin include AMPK-independent and AMPK-dependent effects whereas decrease in glucose level, hyperinsulinemia, and Insulin-like Growth Factor 1 (IGF-1) level are considered its indirect effects. Metformin also decreases both pro-inflammatory cytokines and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF- ΚB) and improves the immune response to cancer cells. Conclusion: Although the results of recent trials confirm the efficacy of metformin in prevention and treatment of different cancers, the evidences are not adequate enough.

Background: Understanding of cervical cancer severity is still an important health issue across the world, especially for developing countries. Cancer or abnormal growth of the cell is one of the major health problems of the world. There are about two hundred types of malignancies reported till date. An updated statistic of all the main types of cancer and pathophysiology of cervical cancer is a significant need for designing the future treatment strategy. Objective: In this review, a brief update on cancer, its causes and different types has been discussed along with updated statistics of patient's mortality. A brief overview of cervical cancer and its pathophysiology has been discussed with special emphasis on its causative agent, human papilloma virus (HPV). A brief introduction and update on genetics, molecular pathogenesis and prevalence of HPV and its role in cervical cancer have been added. Conclusion: This review delivered an updated status of cervical cancer and provide novel therapeutic approaches for targeting HPV. The detailed molecular and genomic information of the HPV help the researchers to develop more effective and efficacious therapeutic strategies and preventive vaccines that will significantly contribute to the control and anticipation of cervical cancer. Ultimately this may open new vistas to get rid of this deadly disease and may offer significant reduction in the numbers of advanced cervical cancers and deaths from cervical cancer in the affected nations.