Dynamic-responsive virus-mimetic nanocapsules facilitate protein drug penetration and extracellular-specific unpacking for antitumor treatment

Li, Yachao; Shen, Cheng; Liang, Xiaoyu; Deng, Kefurong; Zeng, Zenan; Xu, Xianghui

doi:10.1039/d2bm00500j

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Encouraging results have been recently obtained by a biomimetic strategy for versatile and robust TRAIL delivery through the supramolecular construction of virus-mimetic nanocapsules (VMNs) [ 122 ]. VMNs were composed of amphiphilic dendritic peptides mimicking the viral protein component and structure, hydrophobic lipoic acid for driving self-assembly into the capsid-like nanostructures by disulfide bond cross-linking, and dynamic negatively charged decoration.…”

Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

“…Additionally, P-VMNs’ virus-inspired design and the RGD-modified envelope contributed to the deep tumor penetration and accumulation of TRAIL. This virus-mimicking delivery system successfully guided TRAIL to surmount sequential biological barriers and improve the in vivo efficacy [ 122 ].…”

Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

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Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

2023

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The TRAIL (TNF-related apoptosis-inducing ligand) apoptotic pathway is extensively exploited in the development of targeted antitumor therapy due to TRAIL specificity towards its cognate receptors, namely death receptors DR4 and DR5. Although therapies targeting the TRAIL pathway have encountered many obstacles in attempts at clinical implementation for cancer treatment, the unique features of the TRAIL signaling pathway continue to attract the attention of researchers. Special attention is paid to the design of novel nanoscaled delivery systems, primarily aimed at increasing the valency of the ligand for improved death receptor clustering that enhances apoptotic signaling. Optionally, complex nanoformulations can allow the encapsulation of several therapeutic molecules for a combined synergistic effect, for example, chemotherapeutic agents or photosensitizers. Scaffolds for the developed nanodelivery systems are fabricated by a wide range of conventional clinically approved materials and innovative ones, including metals, carbon, lipids, polymers, nanogels, protein nanocages, virus-based nanoparticles, dendrimers, DNA origami nanostructures, and their complex combinations. Most nanotherapeutics targeting the TRAIL pathway are aimed at tumor therapy and theranostics. However, given the wide spectrum of action of TRAIL due to its natural role in immune system homeostasis, other therapeutic areas are also involved, such as liver fibrosis, rheumatoid arthritis, Alzheimer’s disease, and inflammatory diseases caused by bacterial infections. This review summarizes the recent innovative developments in the design of nanodelivery systems modified with TRAIL pathway-targeting ligands.

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Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

Section: Protein-based Systems For Nanodelivery Of Trail Pathway-targ...mentioning

confidence: 99%

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

2023

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Inherent Tumor Microenvironment‐Reversing Hydrogels: Potentiating Molecular Therapy Efficacy Against Drug‐Resistant Tumors

Liang,

Li,

Guo

et al. 2024

Adv Funct Materials

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The tumor microenvironment is a pivotal driver of tumor progression, highlighting the potential of microenvironment reversal as a promising breakthrough in cancer therapy. However, the current tumor microenvironment reversing capacity through targeted drug delivery remains limited, posing a significant challenge in the biomedical field. In this study, a materials science strategy to achieve an inherently efficient reversal of the solid tumor microenvironment while potentiating molecular therapy efficacy against drug‐resistant tumors is proposed. To construct bioactive hydrogel materials, biocompatible and acid‐reversible nanoclays are utilized as building blocks, and peptide polydendrons are designed as supramolecular cross‐linkers. To drive hydrogel network formation, bioactive hydrogels are capable of reversing tumor acidotic microenvironment, integrating superior mechanical properties, injectability, self‐healing capability, and drug‐loading capacity. Through a drug‐resistant cell line in vitro and a tumor‐bearing mouse model in vivo, the hydrogel materials successfully modulate acidic accumulation resulting from tumor metabolic abnormalities and reverse the acidic microenvironment within the tumor tissue. Remarkably, the tumor microenvironment‐reversing hydrogels effectively suppress tumor cell proliferation, migration, and invasion, while significantly amplifying the antitumor drug efficacy. The bioactive hydrogel materials offer an innovative avenue for reversing the tumor microenvironment, displaying promising prospects for clinical translation and applications.

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Bio‐Responsive Macromolecular Drug and Small‐Molecular Drug Conjugates: Nanoparticulate Prodrugs for Tumor Microenvironment Heterogeneity Management and Therapeutic Response Enhancement

Liang

Shen

et al. 2023

Small

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How to break through the poor response of current drug therapy, which often resulted from tumor microenvironment heterogeneity (TMH), remains an enormous challenge in the treatment of critical diseases. In this work, a practical solution on bio‐responsive dual‐drug conjugates for overcoming TMH and improving antitumor treatment, which integrates the advantages of macromolecular drugs and small‐molecular drugs, is proposed. Nanoparticulate prodrugs based on small‐molecular drug and macromolecular drug conjugates are designed as a robust weapon for programmable multidrug delivery at tumor‐specific sites: the tumor microenvironment acid condition triggers delivery of macromolecular aptamer drugs (AX102) to manage TMH (including tumor stroma matrix, interstitial fluid pressure, vasculature network, blood perfusion, and oxygen distribution), and intracellular lysosomal acid condition activates rapid release of small‐molecular drugs (doxorubicin and dactolisib) to enhance curative effects. As compared with doxorubicin chemotherapy, the tumor growth inhibition rate is enhanced by 47.94% after multiple tumor heterogeneity management. This work verifies that the nanoparticulate prodrugs facilitate TMH management and therapeutic response enhancements, as well as elucidates synergetic mechanisms for drug resistance reversal and metastasis inhibition. It is hoped that the nanoparticulate prodrugs will be an excellent demonstration of the co‐delivery of small‐molecular drugs and macromolecular drugs.

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Dynamic-responsive virus-mimetic nanocapsules facilitate protein drug penetration and extracellular-specific unpacking for antitumor treatment

Abstract: Protein-based drugs have been demonstrating great potential on the treatment of various diseases, but most of them encounter many difficulties in clinical trials or uses, such as instability, low bioavailability,...

Cited by 4 publications

References 34 publications

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

Recent Advances in the Development of Nanodelivery Systems Targeting the TRAIL Death Receptor Pathway

Inherent Tumor Microenvironment‐Reversing Hydrogels: Potentiating Molecular Therapy Efficacy Against Drug‐Resistant Tumors

Bio‐Responsive Macromolecular Drug and Small‐Molecular Drug Conjugates: Nanoparticulate Prodrugs for Tumor Microenvironment Heterogeneity Management and Therapeutic Response Enhancement

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