scholarly journals Effect of pH-Responsive Charge-Conversional Polymer Coating to Cationic Reduced Graphene Oxide Nanostructures for Tumor Microenvironment-Targeted Drug Delivery Systems

Nanomaterials ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 1289 ◽  
Author(s):  
Kitae Ryu ◽  
Jaehong Park ◽  
Tae-il Kim
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Targeted Drug Delivery ◽  
Ph Responsive ◽  
Ethylene Imine ◽  
Serum Stability ◽  
Reduced Graphene ◽  
Targeted Drug ◽  
Poly Ethylene ◽  
Targeted Drug Delivery Systems

Tumor tissue represents a slightly acidic pH condition compared to normal tissue due to the accumulation of lactic acids via anaerobic metabolism. In this work, pH-responsive charge-conversional polymer (poly(ethylene imine)-poly(l-lysine)-poly(l-glutamic acid), PKE polymer) was employed for endowing charge-conversional property and serum stability to poly(ethylene imine) conjugated reduced graphene oxide-based drug delivery system (PEI-rGO). Zeta-potential value of PEI-rGO coated with PK5E7 polymer (PK5E7(PEI-rGO)) was −10.9 mV at pH 7.4 and converted to 29.2 mV at pH 6.0, showing pH-responsive charge-conversional property. Sharp-edged plate morphology of PEI-rGO was transformed to spherical nanostructures with vague edges by PK5E7 coating. Size of PK5E7(PEI-rGO) was found to be smaller than that of PEI-rGO in the serum condition, showing its increased serum stability. Loaded doxorubicin (DOX) in PK5E7(PEI-rGO) could be released rapidly in lysosomal condition (pH 5.0, 5 mM glutathione). Furthermore, DOX-loaded PK5E7(PEI-rGO) showed enhanced anticancer activity in HeLa and A549 cells in the tumor microenvironment-mimicking condition (pH 6.0, serum), which would be mediated by non-specific cellular interaction with decorated serum proteins. These results indicate that the pH-responsive charge-conversional PKE polymer coating strategy of cationic rGO nanostructures possesses a potential for acidic tumor microenvironment-targeted drug delivery systems.

scholarly journals pH-Responsive Poly(Ethylene Glycol)-block-Polylactide Micelles for Tumor-Targeted Drug Delivery

2017 ◽  
Vol 18 (9) ◽  
pp. 2711-2722 ◽  
Author(s):  
Lin Xiao ◽  
Lixia Huang ◽  
Firmin Moingeon ◽  
Mario Gauthier ◽  
Guang Yang
Keyword(s):  
Drug Delivery ◽  
Ethylene Glycol ◽  
Targeted Drug Delivery ◽  
Ph Responsive ◽  
Poly Ethylene Glycol ◽  
Targeted Drug ◽  
Poly Ethylene

Recent Advances in Asialoglycoprotein Receptor and Glycyrrhetinic Acid Receptor-Mediated and/or pH Responsive Hepatocellular Carcinoma-Targeted Drug Delivery

2020 ◽  
Vol 27 ◽  
Author(s):  
Yu-Lan Li ◽  
Xiao-Min Zhu ◽  
Hong Liang ◽  
Chris Orvig ◽  
Zhen-Feng Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Asialoglycoprotein Receptor ◽  
Glycyrrhetinic Acid ◽  
Ph Responsive ◽  
Acid Receptor ◽  
Targeted Drug ◽  
Poly Ethylene ◽  
Acid Labile

Background: Hepatocellular carcinoma (HCC) seriously affects human health, especially, it easily develop multi-drug resistance (MDR) result in treatment failure. There is an urgent need to develop highly effective and low-toxicity therapeutic agents to treat HCC and overcome its MDR. Targeted drug delivery systems (DDS) for cancer therapy, including nanoparticles, lipids, micelles and liposomes, have been studied for decades. Recently, more and more attentions have been paid to multifunctional DDS containing various ligands such as polymer moieties, targeting moieties, and acid-labile linkages. The polymer moieties such as poly(ethylene glycol) (PEG), chitosan, hyaluronic acid, pullulan, poly(ethylene oxide) (PEO), poly(propylene oxide) (PPO) protect DDS from degradation. Asialoglycoprotein receptor (ASGPR) and glycyrrhetinic acid receptor (GAR) are the most often used as the targeting moieties, which are overexpressed on hepatocytes. Acid-labile linkage, catering for the pH difference between tumor cells and normal tissue, has been utilized to release drugs at tumor tissue. Objectives: This review provides a summary on the recent progresses in ASGPR and GAR-mediated and/or pH responsive HCC-targeted drug delivery. Conclusion: The multifunctional DDS may prolong systemic circulation, continuously release drugs, increase drugs tumor accumulation at targeted site,enhance anticancer effect, and reduce side effects both in vitro or vivo. But it is rarely used to investigate MDR of HCC, it is need to further study before in clinical.

Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase- 7

2020 ◽  
Vol 20 (27) ◽  
pp. 2459-2471
Author(s):  
Ling-Li Wang ◽  
Bing Zhang ◽  
Ming-Hua Zheng ◽  
Yu-Zhong Xie ◽  
Chang-Jiang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Matrix Metalloproteinases ◽  
Cancer Treatment ◽  
Targeted Drug Delivery ◽  
Selective Inhibitor ◽  
Migration And Invasion ◽  
Side Chains ◽  
Mesenchymal Transition ◽  
Targeted Drug

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.

Recent Advances in the Development of Polymeric Nanocarrier Formulations for the Treatment of Colon Cancer

2019 ◽  
Vol 9 (1) ◽  
pp. 2-14
Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Kiran Thakur ◽  
Tilak R. Bhardwaj ◽  
Deo N. Prasad ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Hyaluronic Acid ◽  
Targeted Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Near Ir ◽  
Targeted Drug ◽  
Poly Ethylene ◽  
Novel Drug

Background: Many efforts have been explored in the last decade to treat colon cancer but nanoparticulate drug delivery systems are making a vital contribution in the improvement of drug delivery to colon cancer cells. Objective: In this review, we attempt to highlight recent advancements in the development of novel drug delivery systems of nanoparticles for the targeted drug delivery to colon. Polymers like Epithelial Cell Adhesion Molecule (EpCAM) aptamer chitosan, Hyaluronic Acid (HA), Chitosan (CS)– Carboxymethyl Starch (CMS), silsesquioxane capped mesoporous silica, Near IR (NIR) fluorescent Human Serum Albumin (HAS), poly(ethylene glycol)-conjugated hyaluronic acid etc. have been discussed by employing various anticancer drugs like doxorubicin, oxaliplatin, paclitaxel, 5-fluorouracil etc. Conclusion: These novel drug delivery systems have been determined to be more efficacious in terms of stability, sustained and targeted drug delivery, therapeutic efficacy, improved bioavailability and enhanced anticancer activity.

scholarly journals Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment

2021 ◽  
Vol 22 (10) ◽  
pp. 5278
Author(s):  
Andrew E. Massey ◽  
Shabnam Malik ◽  
Mohammad Sikander ◽  
Kyle A. Doxtater ◽  
Manish K. Tripathi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Intercellular Communication ◽  
Targeted Drug Delivery ◽  
Clinical Implications ◽  
Disease States ◽  
Significant Research ◽  
The Common ◽  
Targeted Drug ◽  
Loading Methods

Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications.

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