Integrin-mediated active tumor targeting and tumor microenvironment response dendrimer-gelatin nanoparticles for drug delivery and tumor treatment

2015 ◽  
Vol 496 (2) ◽  
pp. 1057-1068 ◽  
Author(s):  
Guanlian Hu ◽  
Huiqing Zhang ◽  
Li Zhang ◽  
Shaobo Ruan ◽  
Qin He ◽  
...  
2020 ◽  
Vol 8 (26) ◽  
pp. 5745-5755
Author(s):  
Rimesh Augustine ◽  
Dae-Kyoung Kim ◽  
Nagendra Kalva ◽  
Kuen Hee Eom ◽  
Jae Ho Kim ◽  
...  

A poly(lysine)-synthetic polymer hybrid nanomicelles were fabricated as promising platform for efficient tumor targeting and glutathione/pH/temperature-responsive anticancer drug delivery.


Author(s):  
Xuexia Tian ◽  
Anhua Shi ◽  
Junzi Wu

Backgroud: At present, the tumor is still the leading cause of death. Biomimetic nanocarriers for precision cancer therapy are attracting increasing attention. Nanocarriers with a good biocompatible surface could reduce the recognition and elimination of nanoparticles as foreign substances by the immune system, offer specific targeting, and improve the efficacy of precision medicine for tumors, thereby providing outstanding prospects for application in cancer therapy. In particular, cell membrane biomimetic camouflaged nanocarriers have become a research hotspot because of their excellent biocompatibility, prolonged circulation in the blood, and tumor targeting. Objective: To summarize the biological targeting mechanisms of different cell membrane-encapsulated nanocarriers in cancer therapy. In this article, the characteristics, application, and stage of progress of bionic encapsulated nanocarriers for different cell membranes are discussed, as are the field’s developmental prospects. Method: The findings on the characteristics of bionic encapsulated nanocarriers for different cell membranes and tumor treatment have been analyzed and summarized. Results: Biomimetic nanosystems based on various natural cell and hybrid cell membranes have been shown to efficiently control targeted drug delivery systems. They can reduce immune system clearance, prolong blood circulation time, and improve drug loading and targeting, thereby enhancing the diagnosis and treatment of tumors and reducing the spread of CTCs. Conclusion: :With advances in the development of biomimetic nanocarrier DDSs, novel ideas for tumor treatment and drug delivery have been developed. However, there are still some problems in biomimetic nanosystems. Therefore, it needs to be optimized through further research, from the laboratory to the clinic for the benefit of a wide range of patients.


2019 ◽  
Vol 7 (9) ◽  
pp. 1503-1509 ◽  
Author(s):  
Qiang Li ◽  
Jun Cao ◽  
Qi Wang ◽  
Jie Zhang ◽  
Shiqin Zhu ◽  
...  

A nanomized NIR fluorescent prodrug was developed with improved bioavailability and tumor-targeting ability. Nanomized tumor-microenvironment-active NIR DCM-S-GEM/PEG prodrug provides a novel approach to realize long real-time tracking of drug delivery and activation process without systemic toxicity in vivo.


Author(s):  
G D Chandrethiya ◽  
P K Shelat ◽  
M N Zaveri

PEGylated gelatin nanoparticles loaded with colchicine were prepared by ethanol precipitation method. Poly-(ethylene glycol)-5000-monomethylether (MPEG 5000), a hydrophilic polymer, was used to pegylate gelatin.  Gluteraldehyde was used as cross-linking agent. To obtain a high quality product, major formulation parameters were optimized.  Spherical particles with mean particles of 193 nm were measured by a Malvern particle size analyzer. Entrapment efficiency was found to be 71.7 ± 1.4% and determined with reverse phase high performance liquid charomatography (RP-HPLC). The in vitro drug release study was performed by dialysis bag method for a period of 168 hours. Lyophilizaton study showed sucrose at lower concentrations proved the best cryoprotectant for this formulation.  Stability study revealed that lyophilized nanoparticles were equally effective (p < 0.05) after one year of storage at 2-8°C with ambient humidity. In vitro antitumoral activity was accessed using the MCF-7 cell line by MTT assay.  The IC50 value was found to be 0.034 μg/ml for the prepared formulation. The results indicate that PEGylated gelatin nanoparticles could be utilized as a potential drug delivery for targeted drug delivery of tumors.  


2017 ◽  
Vol 23 (32) ◽  
pp. 4893-4905 ◽  
Author(s):  
Elena Voronov ◽  
Ron N. Apte

The importance of anti-tumor immunity in the outcome of cancer is now unequivocally established and recent achivements in the field have stimulated the development of new immunotherapeutical approaches. In invasive tumors, widespread inflammation promotes invasiveness and concomitantly also inhibits anti-tumor immune responses. We suggest that efficient tumor treatment should target both the malignant cells and the tumor microenvironment. Interleukin-1 (IL-1) is a pro-inflammatory as well as an immunostimulatory cytokine that is abundant in the tumor microenvironment. Manipulation of IL-1 can thus serve as an immunotherapeutical approach to reduce inflammation/immunosuppression and thus enhance anti-tumor immunity. The two major IL-1 agonistic molecules are IL-1α and IL-1β, which bind to the same IL-1 signaling receptor and induce the same array of biological activities. The IL-1 receptor antagonist (IL-Ra) is a physiological inhibitor of IL-1 that binds to its receptor without transmition of activation signals and thus serves as a decoy target. We have demonstrated that IL-1α and IL-1β are different in terms of the producing cells and their compartmentalization and the amount. IL-1α is mainly expressed intracellularly, in the cytosol, in the nucleus or exposed on the cell membrane, however, it is rarely secreted. IL-1β is active only as a secreted molecule that is mainly produced by activated myeloid cells. We have shown different functions of IL-1α and IL-1β in the malignant process. Thus, in its membrane- associated form, IL-1α is mainly immunostimulatory, while IL-1β that is secreted into the tumor microenvironment is mainly pro-inflammatory and promotes tumorigenesis, tumor invasiveness and immunosuppression. These distinct functions of the IL-1 agonistic molecules are mainly manifested in early stages of tumor development and the patterns of their expression dictate the direction of the malignant process. Here, we suggest that IL-1 modulation can serve as an effective mean to tilt the balance between inflammation and immunity in tumor sites, towards the latter. Different agents that neutralize IL-1, mainly the IL-Ra and specific antibodies, exist. They are safe and FDA-approved. The IL-1Ra has been widely and successfully used in patients with Rheumatoid arthritis, autoinflammatory diseases and various other diseases that have an inflammatory component. Here, we provide the rationale and experimental evidence for the use of anti-IL-1 agents in cancer patients, following first line therapy to debulk the major tumor's mass. The considerations and constraints of using anti-IL-1 treatments in cancer are also discussed. We hope that this review will stimulate studies that will fasten the application of IL-1 neutralization at the bedside of cancer patients.


2019 ◽  
Vol 25 (37) ◽  
pp. 3917-3926
Author(s):  
Sajjad Molavipordanjani ◽  
Seyed Jalal Hosseinimehr

Combination of nanotechnology, biochemistry, chemistry and biotechnology provides the opportunity to design unique nanoparticles for tumor targeting, drug delivery, medical imaging and biosensing. Nanoparticles conjugated with biomolecules such as antibodies, peptides, vitamins and aptamer can resolve current challenges including low accumulation, internalization and retention at the target site in cancer diagnosis and therapy through active targeting. In this review, we focus on different strategies for conjugation of biomolecules to nanoparticles such as inorganic nanoparticles (iron oxide, gold, silica and carbon nanoparticles), liposomes, lipid and polymeric nanoparticles and their application in tumor targeting.


2020 ◽  
Vol 20 (27) ◽  
pp. 2459-2471
Author(s):  
Ling-Li Wang ◽  
Bing Zhang ◽  
Ming-Hua Zheng ◽  
Yu-Zhong Xie ◽  
Chang-Jiang Wang ◽  
...  

Background: Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed. Aims: This study aims to comprehensively review the potentials and advances in applications of MMPs particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery. Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have shown significant targeting applicability at the genetic, protein, and activity levels in both physiological and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases at advanced cancer stages, which can be used for controlled release in cancers in advance stages. Methods: Moreover, this study presents the synthesis and characteristics of a new and highly selective inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics and diagnostics modalities. Results: Our findings showed that the structure of the inhibitor P3’ side chains play the crucial role in developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities against ECM. Conclusion: Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following screening and optimization of the P3’ side chains, with a Ki of 38.6 nM and an inhibitory selectivity of 575 of MMP-7 over MMP-1.


2011 ◽  
Vol 1 (1) ◽  
pp. 67-84
Author(s):  
Zhigang Hu ◽  
Fei Huo ◽  
Yi Zhang ◽  
Chunyang Chen ◽  
Kehua Tu ◽  
...  

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