Enzyme-responsive nano-drug delivery system for combined antitumor therapy

Guo, Fangyuan; Jiao, Yunlong; Du, Yinzhou; Luo, Shuai; Hong, Weiyong; Fu, Qiafan; Li, Aiqin; Wang, Guoping; Yang, Gensheng

doi:10.1016/j.ijbiomac.2022.08.123

Cited by 15 publications

(7 citation statements)

References 42 publications

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“…CAFs in the tumor microenvironment regulate the collagen component of the dense extracellular matrix (ECM), establishing a physical barrier that hinders effective drug delivery. [ 33 ] Hence, the impact of JQ1&PFD@CTL on collagen regulation was investigated. The result of immunohistochemical (IHC) staining showed that the JQ1&PFD@CTL groups effectively suppressed the expression of Ki67 and collagen I, which are markers of tumor proliferation and major constituents of the tumor stroma ( Figure A).…”

Section: Resultsmentioning

confidence: 99%

CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma

Zhang,

Yu,

Zhao

et al. 2023

Advanced Science

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BRD4 is a member of the BET protein family involved in chromatin remodeling and transcriptional regulation. Several BET inhibitors (BETi) have entered clinical trials, demonstrating potential in inducing cancer cell apoptosis and tumor regression. However, resistance to BETi is common in solid tumors. In pancreatic cancer, it is found that cancer‐associated fibroblasts (CAFs) in the tumor microenvironment reduce the BET inhibitor JQ1 sensitivity by inducing BRD4 expression. Moreover, CAFs play a crucial role in the formation of a dense stromal barrier. Therefore, targeting CAFs in the tumor microenvironment of pancreatic cancer not only enhances cancer cells sensitivity to JQ1 but also increases drug perfusion and improves oxygen supply, thus reducing glycolysis and limiting energy supply. To address this challenge, a homologous targeting mechanism utilizing activated fibroblast membrane‐coated liposomes is proposed for specific drug precise target to CAFs‐rich pancreatic cancer. Additionally, TAT peptides enable liposomes penetration, delivering PFD for targeted anti‐fibrotic therapy, reducing extracellular matrix generation and glycolysis, and enhancing JQ1 delivery and sensitivity. In conclusion, the findings indicate the tremendous potential of this CAFs‐targeting liposomal delivery system in pancreatic cancer.

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Section: Resultsmentioning

confidence: 99%

CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma

Zhang,

Yu,

Zhao

et al. 2023

Advanced Science

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“…These modifications enhance the targeting of particles to specific cells, 1478 increasing cellular uptake and, consequently, drug efficacy, as illustrated in Figure 3C. There are primarily two methods for active targeting modifications: one involves the direct modification by covalently bonding ligands to drug carriers with active functional groups; 97 the other uses an indirect modification method where positively charged ligands are inserted into the membrane, 98 as shown in Figure 3D.…”

Section: Surface Modification Techniquesmentioning

confidence: 99%

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs

Liu,

Liang,

Yuhong

et al. 2024

DDDT

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This manuscript offers a comprehensive overview of nanotechnology’s impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

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“…Another new drug delivery system responsive to MMPs was developed using a conjugate of a peptide and polyethylene glycol, and a nanoparticle containing dipentaerythritol (DPE) and PCL were utilized to deliver Cur for tumor treatment. The peptide consisted of an MMP cleavable sequence, GPLGIAG, and a cell permeating peptide, R9, which helped enhance targeting selectivity and cellular uptake after cleavage of GPLGIAG in the tumor microenvironment …”

Section: Mmps-responsive Drug Deliverymentioning

confidence: 99%

“…The peptide consisted of an MMP cleavable sequence, GPLGIAG, and a cell permeating peptide, R9, which helped enhance targeting selectivity and cellular uptake after cleavage of GPLGIAG in the tumor microenvironment. 65 The integration of activable CPPs or their analogues with nanoparticles confers benefits in terms of both rigidity and penetration enhancement, achieved through the cooperative action of shielding and penetration-enhancing effects. It should be noted that various agents with similar functions to activable CPPs exist, and their selection is dependent on the specific type of nanocarrier employed.…”

Section: T H I S C O N T E N T Imentioning

confidence: 99%

Matrix Metalloproteinase-Responsive Drug Delivery Systems

2023

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Matrix metalloproteinases (MMPs) are a class of endopeptidases that are dependent on zinc and facilitate the degradation of extracellular matrix (ECM) proteins, thereby playing pivotal parts in human physiology and pathology. MMPs regulate normal tissue and cellular functions, including tissue development, remodeling, angiogenesis, bone formation, and wound healing. Several diseases, including cancer, inflammation, cardiovascular diseases, and nervous system disorders, have been linked to dysregulated expression of specific MMP subtypes, which can promote tumor progression, metastasis, and inflammation. Various MMP-responsive drug delivery and release systems have been developed by harnessing cleavage activities and overexpression of MMPs in affected regions. Herein, we review the structure, substrates, and physiological and pathological functions of various MMPs and highlight the strategies for designing MMP-responsive nanoparticles to improve the targeting efficiency, penetration, and protection of therapeutic payloads.

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Enzyme-responsive nano-drug delivery system for combined antitumor therapy

Cited by 15 publications

References 42 publications

CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma

CAFs Homologous Biomimetic Liposome Bearing BET Inhibitor and Pirfenidone Synergistically Promoting Antitumor Efficacy in Pancreatic Ductal Adenocarcinoma

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs

Matrix Metalloproteinase-Responsive Drug Delivery Systems

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