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

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.

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Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22105278 ◽

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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pH-responsive antibodies for therapeutic applications

Journal of Biomedical Science ◽

10.1186/s12929-021-00709-7 ◽

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.

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Applications of Nano-drugs and Tumor Microenvironment Sensitive Nano-drug Delivery Systems

2020 9th International Conference on Bioinformatics and Biomedical Science ◽

10.1145/3431943.3431944 ◽

2020 ◽

Author(s):

Anqi Da

Keyword(s):

Drug Delivery ◽

Tumor Microenvironment ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Nano Drug Delivery

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

Journal of Materials Chemistry B ◽

10.1039/c6tb02944b ◽

2017 ◽

Vol 5 (9) ◽

pp. 1734-1741 ◽

Cited By ~ 14

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.

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pH-responded Hollow Fe–Gallic Acid Coordination Polymer for Multimodal Synergistic-therapy and MRI of Cancer

Nanoscale Advances ◽

10.1039/d1na00721a ◽

2021 ◽

Author(s):

Congcong Liu ◽

Chengcheng Li ◽

Sen Jiang ◽

Cheng Zhang ◽

Yang Tian

Keyword(s):

Drug Delivery ◽

Tumor Microenvironment ◽

Coordination Polymer ◽

Cancer Treatment ◽

Gallic Acid ◽

Drug Carriers ◽

Clinical Cancer

Tumor-microenvironment (TME) responding nanostructures are attractive for drug delivery in clinical cancer treatment. The coordination polymer Fe–Gallic Acid (Fe-GA) is one of the promising drug carriers due to its pH-responding,...

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Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots

Nano Letters ◽

10.1021/acs.nanolett.5b04343 ◽

2016 ◽

Vol 16 (2) ◽

pp. 1118-1126 ◽

Cited By ~ 90

Author(s):

Quanyin Hu ◽

Wujin Sun ◽

Yue Lu ◽

Hunter N. Bomba ◽

Yanqi Ye ◽

...

Keyword(s):

Drug Delivery ◽

Tumor Microenvironment

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Design and self-assembly of albumin nanoclusters as a dynamic-covalent targeting co-delivery and stimuli-responsive controlled release platform

Journal of Materials Chemistry B ◽

10.1039/c8tb01791c ◽

2018 ◽

Vol 6 (42) ◽

pp. 6817-6830 ◽

Cited By ~ 1

Author(s):

Wen Liu ◽

Jian Dai ◽

Wei Xue

Keyword(s):

Drug Delivery ◽

Controlled Release ◽

Tumor Microenvironment ◽

Self Assembly ◽

Drug Delivery Systems ◽

Delivery Systems ◽

Stimuli Responsive ◽

Target Sites

Stimuli-responsive nanomaterial-based drug delivery systems that are able to actively target the tumor microenvironment, enhance intratumoral accumulation and release drugs at target sites are attractive therapeutic platforms at present.

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iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

Polymers ◽

10.3390/polym12091906 ◽

2020 ◽

Vol 12 (9) ◽

pp. 1906

Author(s):

Sujin Kang ◽

Sooyeun Lee ◽

Soyeun Park

Keyword(s):

Drug Delivery ◽

Tumor Microenvironment ◽

Chemotherapeutic Agents ◽

Therapeutic Interventions ◽

Treatment Modalities ◽

Neuropilin 1 ◽

Tumor Tissues ◽

Delivery Vehicles ◽

Targeting Ability ◽

Dependent Transport

The unique structure and physiology of a tumor microenvironment impede intra-tumoral penetration of chemotherapeutic agents. A novel iRGD peptide that exploits the tumor microenvironment can activate integrin-dependent binding to tumor vasculatures and neuropilin-1 (NRP-1)-dependent transport to tumor tissues. Recent studies have focused on its dual-targeting ability to achieve enhanced penetration of chemotherapeutics for the efficient eradication of cancer cells. Both the covalent conjugation and the co-administration of iRGD with chemotherapeutic agents and engineered delivery vehicles have been explored. Interestingly, the iRGD-mediated drug delivery also enhances penetration through the blood–brain barrier (BBB). Recent studies have shown its synergistic effect with BBB disruptive techniques. The efficacy of immunotherapy involving immune checkpoint blockades has also been amplified by using iRGD as a targeting moiety. In this review, we presented the recent advances in iRGD technology, focusing on cancer treatment modalities, including the current clinical trials using iRGD. The iRGD-mediated nano-carrier system could serve as a promising strategy in drug delivery to the deeper tumor regions, and be combined with various therapeutic interventions due to its novel targeting ability.

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Applications of Nanoemulsion for the Wound-Healing Process

10.4018/978-1-7998-8378-4.ch021 ◽

2022 ◽

pp. 466-493

Author(s):

S. M. Shaheedha

Keyword(s):

Drug Delivery ◽

Wound Healing ◽

Tumor Microenvironment ◽

Healing Process ◽

Wound Healing Process ◽

Liquid Matrix ◽

Physical Methods ◽

Micro Emulsion ◽

Chronic Injuries ◽

Nano Emulsion

Attention to nanoemulsions has significantly grown in recent years as a result of their unique features like better stability, special appearance, higher performance, and sensorial merits. Chronic injuries are the consequence of a disturbance in the extremely coordinated cataract of wound healing actions. Nevertheless, correlated with variations in the timescales of various physical methods embroiled in tissue renewal, the aggression of the tumor microenvironment, rich in decaying enzymes, as well as its increased pH, demands the use of efficient drug delivery applications. This chapter summarizes that the various stages of wound healing include four phases: hemostatic stage, inflammation, proliferation, and remodeling process, respectively. Moreover, the major reported classes of lipid-based elements were either vesicular (liposome, permeation increased vesicle, etc.), emulsion-based behavior (nano-emulsion and micro-emulsion), or comprise a solid-based liquid matrix in the wound-healing process.

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