scholarly journals Tumor-Microenvironment- Responsive Size-Shrinkable Drug-Delivery Nanosystems for Deepened Penetration Into Tumors

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiaoliang Cheng ◽  
Houli Li ◽  
Xuemei Ge ◽  
Lijuan Chen ◽  
Yao Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Academic Research ◽  
Deep Penetration ◽  
Acidic Ph ◽  
Passive Targeting ◽  
Enhanced Permeability And Retention ◽  
Influence Diffusion ◽  
Cancer Diseases ◽  
Ultrasmall Particles

Over the years, the manipulation and clinical application of drug-delivery nanosystems for cancer diseases have attracted a rapid growth of academic research interests, and some nanodrugs have been approved for clinic application. Although encouraging achievements have been made, the potency of nanomedicines in cancer treatment is far from satisfaction, and one significant reason is the inefficient penetration of nanoparticles into solid tumors. Particle size is one of the most significant features that influence diffusion ability of the drug-delivery system in tumors. Size-shrinkable drug-delivery nanosystems possess a size-switchable property that can achieve passive targeting via the enhanced permeability and retention (EPR) effect and transform into ultrasmall particles in tumors for deep penetration into tumors. The tumor microenvironment is characterized by acidic pH, hypoxia, upregulated levels of enzymes, and a redox environment. In this review, we summarize and analyze the current research progresses and challenges in tumor microenvironment responsive size-shrinkable drug-delivery nanosystems. We further expect to present some meaningful proposals and enlightenments on promoting deep penetration into tumors of nanoparticles.

From Passive Targeting to Personalized Nanomedicine: Multidimensional Insights on Nanoparticles’ Interaction with the Tumor Microenvironment

2020 ◽  
Vol 21 ◽  
Author(s):  
Aya A. Sebak ◽  
Basma M. El-Shenawy ◽  
Sara El-Safy ◽  
Mohamed El-Shazly
Keyword(s):  
Tumor Microenvironment ◽  
Protein Corona ◽  
Lymphatic Drainage ◽  
Biological Macromolecules ◽  
Passive Targeting ◽  
Epr Effect ◽  
The Past ◽  
Current Trends ◽  
Enhanced Permeability And Retention ◽  
Therapeutic Outcomes

: Nanomedicine is revolutionizing the treatment of cancer and has achieved unprecedented outcomes over the past decades. The accumulation of nanoparticles (NPs) in different tumors relies mainly on the enhanced permeability and retention (EPR) effect benefiting from the wide fenestrae of the tumor vasculature and the lack of lymphatic drainage. However, the EPR effect is recognized as a heterogeneous phenomenon resulting in heterogeneous outcomes of clinical trials. Extensive efforts are exerted to enhance the outcomes of nanomedicine in a larger cohort of patients by employing active targeting strategies. However, actively targeted NPs accumulate in tumors by the EPR effect and hence fail to achieve convincing therapeutic outcomes. These obstacles are gradually being removed by improving the understanding of the tumor microenvironment (TME) and the mechanistic interaction of the NPs with its different components. In this review, we provide detailed insights into the past concerns of drug targeting, the current trends of TME reengineering, and the future implications for overcoming past hurdles. Strategies explored in this regard included the use of companion diagnostics and the modulation of the protein corona associated with the systemic administration of NPs and their interaction with biological macromolecules.

Transferrin-Conjugated Nanocarriers as Active-Targeted Drug Delivery Platforms for Cancer Therapy

2017 ◽  
Vol 23 (3) ◽  
pp. 454-466 ◽  
Author(s):  
Daniele R. Nogueira-Librelotto ◽  
Cristiane F. Codevilla ◽  
Ammad Farooqi ◽  
Clarice M. B. Rolim
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Therapeutic Benefit ◽  
Active Targeting ◽  
Future Research ◽  
Passive Targeting ◽  
The Right ◽  
Review Current ◽  
Target Effects

A lot of effort has been devoted to achieving active targeting for cancer therapy in order to reach the right cells. Hence, increasingly it is being realized that active-targeted nanocarriers notably reduce off-target effects, mainly because of targeted localization in tumors and active cellular uptake. In this context, by taking advantage of the overexpression of transferrin receptors on the surface of tumor cells, transferrin-conjugated nanodevices have been designed, in hope that the biomarker grafting would help to maximize the therapeutic benefit and to minimize the side effects. Notably, active targeting nanoparticles have shown improved therapeutic performances in different tumor models as compared to their passive targeting counterparts. In this review, current development of nano-based devices conjugated with transferrin for active tumor-targeting drug delivery are highlighted and discussed. The main objective of this review is to provide a summary of the vast types of nanomaterials that have been used to deliver different chemotherapeutics into tumor cells, and to ultimately evaluate the progression on the strategies for cancer therapy in view of the future research.

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.

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.

scholarly journals pH-responsive antibodies for therapeutic applications

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Tomasz Klaus ◽  
Sameer Deshmukh
Keyword(s):  
Drug Delivery ◽  
Treatment Outcome ◽  
Tumor Microenvironment ◽  
Dependent Manner ◽  
Therapeutic Antibodies ◽  
Ph Responsive ◽  
Biologic Drugs ◽  
Car T ◽  
Ph Dependent ◽  
The Brain

AbstractTherapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood–brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.

Tumor microenvironment responsive biomimetic copper peroxide nanoreactors for drug delivery and enhanced chemodynamic therapy

2021 ◽  
Vol 416 ◽  
pp. 129037
Author(s):  
Shengxin Hou ◽  
Yong-E Gao ◽  
Xianbin Ma ◽  
Yi Lu ◽  
Xinyi Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Copper Peroxide

Coumarin polycaprolactone polymeric nanoparticles: light and tumor microenvironment activated cocktail drug delivery

2017 ◽  
Vol 5 (9) ◽  
pp. 1734-1741 ◽  
Author(s):  
S. Karthik ◽  
Avijit Jana ◽  
M. Selvakumar ◽  
Yarra Venkatesh ◽  
Amrita Paul ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Microenvironment ◽  
Anticancer Drugs ◽  
Polymeric Nanoparticles ◽  
Highly Sensitive

Highly sensitive hypoxia (H2O2)-activated photoresponsive polymeric nanoparticles for cocktail delivery of anticancer drugs doxorubicin (Dox) and chlorambucil (Cbl) were developed.

scholarly journals Novel concept of the smart NIR-light–controlled drug release of black phosphorus nanostructure for cancer therapy

2018 ◽  
Vol 115 (3) ◽  
pp. 501-506 ◽  
Author(s):  
Meng Qiu ◽  
Dou Wang ◽  
Weiyuan Liang ◽  
Liping Liu ◽  
Yin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Near Infrared ◽  
Black Phosphorus ◽  
Deep Penetration ◽  
Nir Light

A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.

scholarly journals Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1151
Author(s):  
Lu Tang ◽  
Jing Li ◽  
Qingqing Zhao ◽  
Ting Pan ◽  
Hui Zhong ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Treatment ◽  
Small Molecule ◽  
Anticancer Agents ◽  
Targeted Drug Delivery ◽  
Treatment Modalities ◽  
Biological Macromolecules ◽  
Passive Targeting ◽  
Efficient Delivery ◽  
Targeted Drug

The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.

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