Correction to: A novel melittin nano-liposome exerted excellent anti-hepatocellular carcinoma efficacy with better biological safety

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.     

Engineered magnetic core shell nanoprobes:Synthesis and applications to cancer imaging and therapeutics

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.     

β-连环蛋白：卵巢癌治疗的新靶点

卵巢癌是致死率最高的妇科肿瘤,早期不易发现。常规手术及放化疗均难以明显提高患者的远期生存率,因此寻求新的治疗方法迫在眉睫。β-连环蛋白（β-catenin）作为E-cadherin（E-钙调蛋白）/β-连环蛋白系统和Wnt信号通路中的关键分子,在多种肿瘤的发生、发展过程中起着重要作用。我们主要阐述了β-连环蛋白在各类卵巢癌中的表达情况及针对β-连环蛋白分子的一些靶向治疗手段。     

Minicells: versatile vectors for targeted drug or si/shRNA cancer therapy

Effective cancer therapy continues to be a daunting challenge due mainly to considerable tumor cell heterogeneity, drug-resistance, and dose-limiting toxicity of therapeutics. Here we review a versatile nano-cellular (minicell) delivery vehicle that can be packaged with therapeutically effective concentrations of chemotherapeutic drugs, siRNAs or shRNAs and can be targeted to tumors via minicell-surface attached bispecific antibodies. A range of minicell-based therapeutics have shown highly effective tumor stabilization/regression in the murine xenograft model and in case studies in canines with late-stage endogenous tumors. Repeat intravenous dosing shows absence of toxicity or immunogenicity in both species. The minicell-based therapeutic has potential applications in personalized cancer medicine.     

The biochemical and molecular mechanisms involved in the role of tumor micro-environment stress in development of drug resistance

BackgroundMulti-drug resistance (MDR) is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Moreover, the tumor micro-environment is essential to the formation of drug resistant cancers. Recent evidence indicates that the tumor micro-environment is a critical regulator of cancer progression, distant metastasis and acquired resistance of tumors to various therapies. Despite significant advances in chemotherapy and radiotherapy, the development of therapeutic resistance leads to reduced drug efficacy.Scope of reviewThis review highlights mechanistic aspects of the biochemistry of the tumor micro-enviroment, such as the hypoglycaemia, reactive oxygen species (ROS), hypoxia and their effects in propagating MDR. This is achieved through: (A) increased survival via autophagy and failure of apoptosis; (B) altered metabolic processing; and (C) reduction in drug delivery and uptake or increased drug efflux.Major conclusionsThe development of MDR in cancer has been demonstrated to be majorly influenced by naturally occurring stressors within the tumor micro-environment, as well as chemotherapeutics. Thus, the tumor micro-environment is currently emerging as a major focus of research which needs to be carefully addressed before cancer can be successfully treated.General significanceElucidating the biochemical mechanisms which promote MDR is essential in development of effective therapeutics that can overcome these acquired defences in cancer cells.     

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.     

Multifunctional synthetic poly(L-glutamic acid)-based cancer therapeutic and imaging agents

Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers that have been increasingly studied as efficient carriers for drugs and imaging agents. Synthetic biocompatible polymers have been used to improve the efficacy of both small-molecular-weight therapeutics and imaging agents. Furthermore, multiple targeted anticancer agents and/or imaging reporters can be attached to a single polymer chain, allowing multifunctional and/or multimodality therapy and molecular imaging. Having both an anticancer drug and an imaging reporter in a single polymer chain allows noninvasive real-time visualization of the pharmacokinetics of polymeric drug delivery systems, which can uncover and explain the complicated mechanisms of in vivo drug delivery and their correlation to pharmacodynamics. This review examines the use of the synthetic biocompatible polymer poly(L-glutamic acid) (PG) as an efficient carrier of cancer therapeutics and imaging agents. This review summarizes and updates our recent research on the use of PG as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL), the combination of PG-TXL with radiotherapy, mechanisms of action of PG-TXL, and noninvasive visualization of in vivo delivery of polymeric conjugates with contrast-enhanced magnetic resonance imaging, optical imaging, and multimodality imaging.     

In Vivo Bioluminescent Imaging of Irradiated Orthotopic Pancreatic Cancer Xenografts in Nonobese Diabetic-Severe Combined Immunodeficient Mice: A Novel Method for Targeting and Assaying Efficacy of Ionizing Radiation

Adenocarcinoma of the pancreas is a lethal malignancy, and better models to study tumor behavior in vivo are needed for the development ofmore effective therapeutics. Ionizing radiation is a treatment modality that is commonly used in the clinical setting, in particular, for locally confined disease; however, good model systems to study the effect of ionizing radiation in orthotopic tumors have not been established. In an attempt to create clinically relevant models for studying treatments directed against pancreatic cancer, we have defined a methodology to measure the effect of varying doses of radiation in established human pancreatic cancer orthotopic xenografts using two different pancreatic cancer cell lines (Panc-1 and BXPC3) infected with a lentiviral vector expressing CMV promoter-driven luciferase to allow bioluminescence imaging of live animals in real time. Quantifiable photon emission from luciferase signaling in vivo correlated well with actual tumor growth. Bioluminescence imaging of the established pancreatic xenografts was used to direct delivery of radiation to the orthotopic tumors and minimize off-target adverse effects. Growth delay was observed with schedules in the range of 7.5 Gy in five fractions to 10 Gy in four fractions, whereas doses 3 Gy or higher produced toxic adverse effects. In conclusion, we describe a model in which the effects of ionizing radiation, alone or in combination with other therapeutics, in orthotopic xenografts, can be studied.     

Magnetic force microscopy analysis of apoptosis of HL-60 cells induced by complex of antisense oligonucleotides and magnetic nanoparticles

Magnetic force microscopy (MFM) has been employed to observe antisense oligonucleotides (ASOs)-coupled silica-coated magnetic iron oxide nanoparticles (SMNPs) internalized into human leukemia (HL-60) cells. The experiment demonstrated that the ASOs-coupled SMNPs delivery into the cells really occurred. The nanoparticles were internalized into the cells and the apoptotic topography can be directly visualized simultaneously with MFM technology. These present observations offer direct morphology evidence on studying the apoptosis of tumor cells and provide useful information for better design of new diagnostic and therapeutic tools in tumor treatment.     

Fabrication and Intracellular Delivery of Doxorubicin/Carbonate Apatite Nanocomposites: Effect on Growth Retardation of Established Colon Tumor

In continuing search for effective treatments of cancer, the emerging model aims at efficient intracellular delivery of therapeutics into tumor cells in order to increase the drug concentration. However, the implementation of this strategy suffers from inefficient cellular uptake and drug resistance. Therefore, pH-sensitive nanosystems have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms in endosomal or lysosomal acidic pH along with endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. Here, novel pH sensitive carbonate apatite has been fabricated to efficiently deliver anticancer drug Doxorubicin (DOX) to cancer cells, by virtue of its pH sensitivity being quite unstable under an acidic condition in endosomes and the desirable size of the resulting apatite-DOX for efficient cellular uptake as revealed by scanning electron microscopy. Florescence microscopy and flow cytometry analyses demonstrated significant uptake of drug (92%) when complexed with apatite nanoparticles. In vitro chemosensitivity assay revealed that apatite-DOX nanoparticles executed high cytotoxicity in several human cancer cell lines compared to free drugs and consequently apatite-DOX-facilitated enhanced tumor inhibitory effect was observed in colorectal tumor model within BALB/cA nude mice, thereby shedding light on their potential applications in cancer therapy.     

Structurally flexible triethanolamine-core poly(amidoamine) dendrimers as effective nanovectors to deliver RNAi-based therapeutics

RNAi-based nucleic acid molecules have attracted considerable attention as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing nanocarriers for nucleic acid delivery thanks to their unique well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure. The present review offers a brief overview of the structurally flexible triethanolamine-core poly(amidoamine) (PAMAM) dendrimers developed in our group as nanovectors for the delivery of RNAi therapeutics. Their excellent activity for delivering different RNAi therapeutics in various disease models in vitro and in vivo will be highlighted here.     

Progress in the application of exosomes as therapeutic vectors in tumor-targeted therapy

Cancer is the second leading cause of death in the world with a high annual incidence level. Researchers have been working on developing treatments for cancer. Targeted therapy is an emerging treatment modality that is more novel than surgery, radiotherapy and chemotherapy. In targeted therapy, exogenous nanoscale microparticles are applied as carriers for drugs or genes. However, conventional particles have certain limitations attributed to non-specific cytotoxicity, biocompatibility and low delivery efficacy in individual therapeutic vector systems. Exosomes are small vesicles secreted by various cells that consist of lipid bilayer membranes without organelles. Due to their excellent biocompatibility, exosomes have received increased attention in recent years for targeted therapy applications. This review briefly introduces the current status of targeted therapy, and exosomes are introduced by their structural characteristics, physiological effects and separation methods. This review also discusses the applications of engineered exosomes derived from different cells in the field of targeted therapies and compares the two-way regulation of mesenchymal stromal cell–derived exosomes in tumor therapy.     

Potential of bacterial culture media in biofabrication of metal nanoparticles and the therapeutic potential of the as-synthesized nanoparticles in conjunction with artemisinin against MDA-MB-231 breast cancer cells

In the recent past, various groups have proposed diverse biocompatible methods for the synthesis of metal nanoparticles (NPs). Besides culture biomass, culture supernatants (CS) are increasingly being explored for the synthesis of NPs; however, with the ever-increasing exploration of various CS in the biofabrication of NPs, it is equally important to explore the potential of various culture media (CMs) in the synthesis of metal NPs. Considering these aspects, in the present investigation, we explore the possible applicability of various CMs in the biofabrication of metal NPs. The synthesis of NPs was primarily followed by UV/VIS spectroscopy, and, thereafter, the NPs were characterized by various physiochemical techniques, including EM, EDX, FT_IR, X-ray diffraction, and DLS measurements, and finally, their anticancer potentialities were investigated against breast cancer. In addition, the NPs were examined in conjunction with artemisinin for therapeutic benefits against aggressive and highly metastatic MDA-MB-231 breast cancer cells. Cumulatively, the results of the present study collated the potentials of various bacterial CMs in the biofabrication of metal NPs and ascertained the efficacy of the as-synthesized silver nanoparticles, especially the combinatorial entity as intriguing breast cancer therapeutics. The data of the present study plausibly assist in advancing the therapeutic applicability of the combinatorial amalgam against aggressive and highly metastatic MDA-MB-231 breast cancer cells.     

The viral approach to breast cancer immunotherapy

Despite years of intensive research, breast cancer remains the leading cause of death in women worldwide. New technologies including oncolytic virus therapies, virus, and phage display are among the most powerful and advanced methods that have emerged in recent years with potential applications in cancer prevention and treatment. Oncolytic virus therapy is an interesting strategy for cancer treatment. Presently, a number of viruses from different virus families are under laboratory and clinical investigation as oncolytic therapeutics. Oncolytic viruses (OVs) have been shown to be able to induce and initiate a systemic antitumor immune response. The possibility of application of a multimodal therapy using a combination of the OV therapy with immune checkpoint inhibitors and cancer antigen vaccination holds a great promise in the future of cancer immunotherapy. Display of immunologic peptides on bacterial viruses (bacteriophages) is also increasingly being considered as a new and strong cancer vaccine delivery strategy. In phage display immunotherapy, a peptide or protein antigen is presented by genetic fusions to the phage coat proteins, and the phage construct formulation acts as a protective or preventive vaccine against cancer. In our laboratory, we have recently tested a few peptides (E75, AE37, and GP2) derived from HER2/neu proto-oncogene as vaccine delivery modalities for the treatment of TUBO breast cancer xenograft tumors of BALB/c mice. Here, in this paper, we discuss the latest advancements in the applications of OVs and bacterial viruses display systems as new and advanced modalities in cancer immune therapeutics.     

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

An often overlooked issue in the field of adenovirus (Ad)-mediated cancer gene therapy is its limited capacity for effective systemic delivery. Although primary tumors can be treated effectively with intralesional injection of conventional Ad vectors, systemic metastasis is difficult to cure. Systemic administration of conventional naked Ads leads to acute accumulation of Ad particles in the liver, induction of neutralizing antibody, short blood circulation half-life, non-specific biodistribution in undesired organs, and low selective accumulation in the target disease site. Versatile strategies involving the modification of viral surfaces with polymers and nanomaterials have been designed for the purpose of maximizing Ad anti-tumor activity and specificity by systemic administration. Integration of viral and non-viral nanomaterials will substantially advance both fields, creating new concepts in gene therapeutics. This review focuses on current advances in the development of smart Ad hybrid nanocomplexes based on various design-based strategies for optimal Ad systemic administration.     

Nanoparticle-mediated targeted drug delivery for breast cancer treatment

Breast cancer (BC) is the most common malignancy in women worldwide, and one of the deadliest after lung cancer. Currently, standard methods for cancer therapy including BC are surgery followed by chemotherapy or radiotherapy. However, both chemotherapy and radiotherapy often fail to treat BC due to the side effects that these therapies incur in normal tissues and organs. In recent years, various nanoparticles (NPs) have been discovered and synthesized to be able to selectively target tumor cells without causing any harm to the healthy cells or organs. Therefore, NPs-mediated targeted drug delivery systems (DDS) have become a promising technique to treat BC. In addition to their selectivity to target tumor cells and reduce side effects, NPs have other unique properties which make them desirable for cancer treatment such as low toxicity, good compatibility, ease of preparation, high photoluminescence (PL) for bioimaging in vivo, and high loadability of drugs due to their tunable surface functionalities. In this study, we summarize with a critical analysis of the most recent therapeutic studies involving various NPs-mediated DDS as alternatives for the traditional treatment approaches for BC. It will shed light on the significance of NPs-mediated DDS and serve as a guide to seeking for the ideal methodology for future targeted drug delivery for an efficient BC treatment.     

Fiat Lux: selective delivery of high flux of nitric oxide (NO) to biological targets using photoactive metal nitrosyls

In addition to its beneficial roles in blood pressure regulation, immune response, neurotransmission, and redox balance, nitric oxide (NO) can induce cellular apoptosis at relatively high concentrations. Since photoactive metal nitrosyls can deliver NO under the control of light, they are uniquely suited as NO drugs in photodynamic therapy (PDT) to destroy cancer cells. Stable and photoactive metal nitrosyls can first be placed in close proximity of a malignant site and then triggered via pulses of light to deliver high flux of NO. During the past few years, a number of such metal-based 'NO carriers' have been synthesized and tuned for rapid release of NO upon exposure to UV or visible light. Using various chromophore conjugation strategies, attempts are now being made to photosensitize the M-NO bond to infrared light. Progress has also been made in incorporating metal nitrosyls into biocompatible matrices for site-specific delivery of NO to tumors. A combination of light and NO could offer a viable treatment modality for cancer.     

纳米药物递送系统在前列腺癌治疗中的应用

前列腺癌（PCa）是全球最常见的男性泌尿生殖系统恶性肿瘤。手术、内分泌治疗、放疗和化疗是PCa的主要临床治疗选择。纳米药物递送系统具有良好的可控释放特性和较好的肿瘤靶向能力，并可通过增强的渗透性和保留（EPR）效应被动靶向肿瘤。通过精巧的设计组装和外表修饰赋予纳米递药系统与众不同的肿瘤治疗效果。本文介绍用于PCa治疗的先进纳米药物递送系统以及未来发展。     

Application of nanotechnology in biomedicine

Nanotechnology is the development of engineered devices at the atomic, molecular and macromolecular level in nanometer range. Nanoparticles have potential application in medical field including diagnostics and therapeutics. Nanotechnology devices are being developed for diagnosis of cancer and infectious diseases which can help in early detection of the disease. Advances in nanotechnology also proved beneficial in therapeutic field such as drug discovery, drug delivery and gene/protein delivery. Nanoparticles can be constructed by various methodology so that effect can be targeted at desired site. In this review, some of the applications of nanoparticles in medicine as diagnostics and therapeutics which can be employed safely at the clinical level have been described. On other hand, as the particles become generally smaller their likehood of causing harm to the lung increases. Therefore, there is a need to study safety of nanoparticles.