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cascade nanomedicine

Chenfeng Xu, Yu Sun, Yulin Yu, Mei Hu, Conglian Yang, Zhiping Zhang
An intravenously administered drug delivery system should undergo a five-step 'CAPIR' cascade (circulation, accumulation, penetration, internalization and release), and the maximal efficiency of each step is of great importance to obtain the improved final therapeutic benefits and overall survival rate. Here, a pH/matrix metalloproteinase-9 (MMP9) sequentially responsive and continuously structure-transformable nanoparticle assembled from a doxorubicin (DOX)-conjugated peptide was exploited for comprehensively improving the 'CAPIR cascade' and eventually enhancing the therapeutic efficacy...
January 2, 2019: Nanoscale
Zhimei He, Yunlu Dai, Xiangli Li, Dan Guo, Yijing Liu, Xiaolin Huang, Jingjing Jiang, Sheng Wang, Guizhi Zhu, Fuwu Zhang, Lisen Lin, Jun-Jie Zhu, Guocan Yu, Xiaoyuan Chen
During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2 -consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia-activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido-/photosensitizer-terminated UiO-66 nanoscale metal-organic frameworks (UiO-66-H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered...
December 19, 2018: Small
Jitender Bariwal, Virender Kumar, Yuxiang Dong, Ram I Mahato
Hedgehog (Hh) signaling is involved in the initiation and progression of various cancers and is essential for embryonic and postnatal development. This pathway remains in the quiescent state in adult tissues but gets activated upon inflammation and injuries. Inhibition of Hh signaling pathway using natural and synthetic compounds has provided an attractive approach for treating cancer and inflammatory diseases. While the majority of Hh pathway inhibitors target the transmembrane protein Smoothened (SMO), some small molecules that target the signaling cascade downstream of SMO are of particular interest...
November 28, 2018: Medicinal Research Reviews
Cheng Teng Ng, Liya E Yu, Choon Nam Ong, Boon Huat Bay, Gyeong Hun Baeg
Nanomaterials (NMs) are widely used in consumer and industrial products, as well as in the field of nanomedicine. Despite their wide array of applications, NMs are regarded as foreign entities by the body and thus induce various immune reactions. In mammals, NMs trigger differential recognition by immune cells such as macrophages, causing perturbation of the immune system. Studies on the pattern recognition of NMs have revealed that the Toll-like receptor signaling pathway plays an essential role in NM-induced innate immunity...
November 19, 2018: Nanotoxicology
Huanli Sun, Yangyang Dong, Jan Feijen, Zhiyuan Zhong
The advancement of tissue and cell-specific drug delivery systems is a key to precision cancer therapy. Peptides, with easy synthesis, low immunogenicity and biological functions closely mimicking or surpassing natural proteins, have been actively engineered and explored to provide nanomedicines with the ability to overcome various extracellular and intracellular delivery barriers ranging from phagocytic clearance in the circulation, low tumor penetration, poor cancer cell selectivity, inferior cell penetration, to endosomal entrapment as well as poor blood brain barrier permeation for brain cancer therapy...
November 28, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Filippo Pierini, Paweł Nakielski, Olga Urbanek, Sylwia Pawłowska, Massimiliano Lanzi, Luciano De Sio, Tomasz Aleksander Kowalewski
Materials for the treatment of cancer have been studied comprehensively over the past few decades. Among the various kinds of biomaterials, polymer-based nanomaterials represent one of the most interesting research directions in nanomedicine because their controlled synthesis and tailored designs make it possible to obtain nanostructures with biomimetic features and outstanding biocompatibility. Understanding the chemical and physical mechanisms behind the cascading stimuli-responsiveness of smart polymers is fundamental for the design of multifunctional nanomaterials to be used as photothermal agents for targeted polytherapy...
October 5, 2018: Biomacromolecules
Marziyeh Hajialyani, Devesh Tewari, Eduardo Sobarzo-Sánchez, Seyed Mohammad Nabavi, Mohammad Hosein Farzaei, Mohammad Abdollahi
Wound healing process is an intricate sequence of well-orchestrated biochemical and cellular phenomena to restore the integrity of the skin and subcutaneous tissue. Several plant extracts and their phytoconstituents are known as a promising alternative for wound healing agents due to the presence of diverse active components, ease of access, and their limited side effects. The development of nanotechnological methods can help to improve the efficacy of different therapeutics as well as herbal-based products...
2018: International Journal of Nanomedicine
Shana J Cameron, Farah Hosseinian, William G Willmore
Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges from 1 to 100 nanometers in diameter. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism on which it is tested, are all large determining factors on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signalling that can eventually trigger organelle autophagy and apoptosis...
July 12, 2018: International Journal of Molecular Sciences
Susheel Kumar Nethi, Ayan Kumar Barui, Sudip Mukherjee, Chitta Ranjan Patra
SIGNIFICANCE: Redox signaling plays a vital role in regulating various cellular signaling pathways and disease biology. Recently, nanomedicine (application of nanotechnology in biology and medicine) has been demonstrated to regulate angiogenesis through redox signaling. A complete understanding of redox signaling pathways influenced angiogenesis/antiangiogenesis triggered by therapeutic nanoparticles is extensively reviewed in this article. Recent Advances: In recent times, nanomedicines are regarded as the Trojan horses that could be employed for successful drug delivery, gene delivery, peptide delivery, disease diagnosis, and others, conquering barriers associated with conventional theranostic approaches...
August 24, 2018: Antioxidants & Redox Signaling
Nikola Geskovski, Simona Dimchevska Sazdovska, Silvana Gjosheva, Rumenka Petkovska, Mirjana Popovska, Liljana Anastasova, Kristina Mladenovska, Katerina Goracinova
Recent advances in understanding the etiology and pathogenesis of periodontal disease and polymicrobial synergy in the dysbiotic oral microbial community endorsed novel therapeutic targets and assured further improvement in periodontal disease treatment. Moreover, understanding of the events at the molecular level inspired the researchers to alleviate the stress from the disease by applying the bottom-up approach and delivering the drugs at the site of action, using nanoscale medicines. This review is focused on promising strategies for rational design of nanopaharmaceuticals for periodontal disease treatment based on novel therapeutic targets and the potential of advanced concepts for inflammation cascade targeting...
May 14, 2018: Archives of Oral Biology
Ailar Nakhlband, Morteza Eskandani, Yadollah Omidi, Nazli Saeedi, Samad Ghaffari, Jaleh Barar, Alireza Garjani
Introduction: Cardiovascular diseases (CVDs) is recognized as the leading cause of mortality worldwide. The increasing prevalence of such disease demands novel therapeutic and diagnostic approaches to overcome associated clinical/social issues. Recent advances in nanotechnology and biological sciences have provided intriguing insights to employ targeted Nanomachines to the desired location as imaging, diagnosis, and therapeutic modalities. Nanomedicines as novel tools for enhanced drug delivery, imaging, and diagnosis strategies have shown great promise to combat cardiovascular diseases...
2018: BioImpacts: BI
Cristina Fornaguera, Miguel Ángel Lázaro, Pau Brugada-Vilà, Irene Porcar, Ingrid Morera, Marta Guerra-Rebollo, Cristina Garrido, Núria Rubio, Jerónimo Blanco, Anna Cascante, Salvador Borrós
Glioblastoma multiforme (GBM) is the most devastating primary brain tumor due to its infiltrating and diffuse growth characteristics, a situation compounded by the lack of effective treatments. Currently, many efforts are being devoted to find novel formulations to treat this disease, specifically in the nanomedicine field. However, due to the lack of comprehensive characterization that leads to insufficient data on reproducibility, only a reduced number of nanomedicines have reached clinical phases. In this context, the aim of the present study was to use a cascade of assays that evaluate from physical-chemical and structural properties to biological characteristics, both in vitro and in vivo, and also to check the performance of nanoparticles for glioma therapy...
November 2018: Drug Delivery
Yunlu Dai, Zhen Yang, Siyuan Cheng, Zhongliang Wang, Ruili Zhang, Guizhi Zhu, Zhantong Wang, Bryant C Yung, Rui Tian, Orit Jacobson, Can Xu, Qianqian Ni, Jibin Song, Xiaolian Sun, Gang Niu, Xiaoyuan Chen
Engineering functional nanomaterials with high therapeutic efficacy and minimum side effects has increasingly become a promising strategy for cancer treatment. Herein, a reactive oxygen species (ROS) enhanced combination chemotherapy platform is designed via a biocompatible metal-polyphenol networks self-assembly process by encapsulating doxorubicin (DOX) and platinum prodrugs in nanoparticles. Both DOX and platinum drugs can activate nicotinamide adenine dinucleotide phosphate oxidases, generating superoxide radicals (O2 •- )...
February 2018: Advanced Materials
Lewis D Blackman, Spyridon Varlas, Maria C Arno, Alice Fayter, Matthew I Gibson, Rachel K O'Reilly
Enzyme loading of polymersomes requires permeability to enable them to interact with the external environment, typically requiring addition of complex functionality to enable porosity. Herein, we describe a synthetic route towards intrinsically permeable polymersomes loaded with functional proteins using initiator-free visible light-mediated polymerization-induced self-assembly (photo-PISA) under mild, aqueous conditions using a commercial monomer. Compartmentalization and retention of protein functionality was demonstrated using green fluorescent protein as a macro-molecular chromophore...
October 31, 2017: ACS Macro Letters
Wendong Ke, Wei Yin, Zengshi Zha, Jean Felix Mukerabigwi, Weijian Chen, Yuheng Wang, Chuanxin He, Zhishen Ge
Block copolymer prodrugs (BCPs) have attracted considerable attentions in clinical translation of nanomedicine owing to their self-assembly into well-defined core-shell nanoparticles for improved pharmacokinetics, stability in blood circulation without drug leakage, and optimized biodistribution. However, a cascade of physiological barriers against specific delivery of drugs into tumor cells limit the final therapeutic efficacy. Herein, we report a robust and facile strategy based on thiolactone chemistry to fabricate well-defined BCPs with sequential tumor pH-promoted cellular internalization and intracellular stimuli-responsive drug release...
February 2018: Biomaterials
Larissa Kotelevets, Eric Chastre, Joachim Caron, Julie Mougin, Gerard Bastian, Alain Pineau, Francine Walker, Therese Lehy, Didier Desmaële, Patrick Couvreur
Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination...
June 1, 2017: Cancer Research
Tanushree Malik, Gaurav Chauhan, Goutam Rath, R S R Murthy, Amit K Goyal
More than 35 million people are living with HIV worldwide with approximately 2.3 million new infections per year. Cascade of events (cell entry, virus replication, assembly and release of newly formed virions) is involved in the HIV-1 transmission process. Every single step offers a potential therapeutic strategy to halt this progression and HIV fusion into the human host cell is one such stage. Controlling the initial event of HIV-1 transmission is the best way to control its dissemination especially when prophylaxis is concerned...
November 2017: Drug Delivery
Qihang Sun, Zhuxian Zhou, Nasha Qiu, Youqing Shen
Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency...
April 2017: Advanced Materials
Morteza Eskandani, Somayeh Vandghanooni, Jaleh Barar, Hossein Nazemiyeh, Yadollah Omidi
Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions...
June 2017: International Journal of Biological Macromolecules
Zijian Zhou, Jibin Song, Liming Nie, Xiaoyuan Chen
The reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, a photosensitizer (PS) and oxygen, which greatly favors the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) the limited penetration depth of light, which restricts traditional PDT to superficial tumours; (ii) oxygen reliance does not allow PDT treatment of hypoxic tumours; (iii) light can complicate the phototherapeutic outcomes because of the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects from undesirable white-light activation and self-catalysation of traditional PSs...
November 21, 2016: Chemical Society Reviews
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