Exocytosis blockade of endoplasmic reticulum-targeted nanoparticle enhances immunotherapy

Chen, Liqiang; Liu, Chendong; Xiang, Yucheng; Lyu, Jiayan; Zhou, Zhou; Gong, Tao; Gao, Huile; Li, Lian; Huang, Yuan

doi:10.1016/j.nantod.2021.101356

Cited by 22 publications

(20 citation statements)

References 49 publications

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“…The central aim of immunotherapy is to harness autologous immune responses for tumor elimination [ 1 , 4 , 5 , 6 , 7 , 8 ]. Distinct from conventional approaches such as surgery, chemotherapy, and radiotherapy, the modulation of the immune system can lead to abscopal and long-lasting therapeutic consequences, therefore preventing tumor recurrence and metastasis [ 9 , 10 , 11 ]. Hitherto, most clinically approved immune-intervening agents are macromolecules, such as blockade antibodies, engineered immune cells, oncolytic viruses, cytokines/chemokines, and vaccines [ 2 , 10 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

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Unsatisfactory physicochemical properties of macromolecular drugs seriously hinder their application in tumor immunotherapy. However, these problems can be effectively solved by small-molecule compounds. In the promising field of small-molecule drug development, proteolysis targeting chimera (PROTAC) offers a Cancer Patients. Bosn. J. Basic novel mode of action in the interactions between small molecules and therapeutic targets (mainly proteins). This revolutionary technology has shown considerable impact on several proteins related to tumor survival but is rarely exploited in proteins associated with immuno-oncology up until now. This review attempts to comprehensively summarize the well-studied and less-developed immunological targets available for PROTAC technology, as well as some targets to be explored, aiming to provide more options and opportunities for the development of small-molecule-based tumor immunotherapy. In addition, some novel directions that can magnify and broaden the protein degradation efficiency are mentioned to improve PROTAC design in the future.

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Section: Introductionmentioning

confidence: 99%

Small-Molecule PROTACs for Cancer Immunotherapy

Liu¹,

Zhang²,

Xiang³

et al. 2022

Molecules

Self Cite

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“…Monoclonal antibodies against checkpoint molecules such as programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) have yielded unprecedent success in CRC patients ( 9 , 10 ). Some small-molecule compounds that directly inhibit PD-1/PD-L1 interaction ( 11 , 12 ) and its regulatory proteins, such as bromodomain and extra-terminal domain (BET) ( 13 , 14 ) and Src homology 2 domain containing protein tyrosine phosphatase (SHP2) ( 15 , 16 ), as well as inhibitors of other immune checkpoints (CD47, CTLA-4, V-domain Ig suppressor of T-cell activation (VISTA)) ( 17 , 18 ), are also under pre-clinical investigations. However, only highly mutated CRC patients (about 15% of total cases) that are mismatch repair deficient (dMMR) or exhibit high levels of microsatellite instability (MSI-H) can benefit from ICIs.…”

Section: Introductionmentioning

confidence: 99%

“…During blood circulation, ICIs, especially small molecules, are difficult to accumulate in tumor beds. Macrophage-mediated phagocytosis system attenuates the delivery efficiency of ICIs ( 13 ). Even after entering CRC tissues, the amphiphilic cell membranes, lysosome degradation, and subcellular barriers (such as nuclear membranes, mitochondrial membranes, and endoplasmic reticulum membranes) also hinder the efficacy of ICIs ( 26 ).…”

Section: Introductionmentioning

confidence: 99%

Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology

Liu

Xiang²,

Zheng³

et al. 2022

Front. Immunol.

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Immune checkpoint blockade (ICB) has gained unparalleled success in the treatment of colorectal cancer (CRC). However, undesired side effects, unsatisfactory response rates, tumor metastasis, and drug resistance still hinder the further application of ICB therapy against CRC. Advancing ICB with nanotechnology can be game-changing. With the development of immuno-oncology and nanomaterials, various nanoplatforms have been fabricated to enhance the efficacy of ICB in CRC treatment. Herein, this review systematically summarizes these recent nano-strategies according to their mechanisms. Despite their diverse and complex designs, these nanoplatforms have four main mechanisms in enhancing ICB: 1) targeting immune checkpoint inhibitors (ICIs) to tumor foci, 2) increasing tumor immunogenicity, 3) remodeling tumor microenvironment, and 4) pre-sensitizing immune systems. Importantly, advantages of nanotechnology in CRC, such as innovating the mode-of-actions of ICB, modulating intestinal microbiome, and integrating the whole process of antigen presentation, are highlighted in this review. In general, this review describes the latest applications of nanotechnology for CRC immunotherapy, and may shed light on the future design of ICB platforms.

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“…Polymer nanoparticles (e.g., PLGA nanoparticles) surface‐coated with cytoplasmic membrane or membranes of subcellular organelles by ultrasonic method or co‐extrusion can inherit the biological features of the source cells, facilitating the site‐specific tissue penetration, cellular uptake, and intracellular distribution of cargos. It has been confirmed that nanoparticles camouflaged with specific types and/or compositions of membrane demonstrate certain tropism for ER, which can be further optimized to achieve an ideal targeting effect (L. Chen et al, 2022; Y. Li et al, 2020; W. Zhang, Yu, et al, 2019).…”

Section: Endoplasmic Reticulum: the Protein And Lipid Production Factorymentioning

confidence: 99%

“…Based on the fact that vesicle‐SNARE (v‐SNARE) protein in the ER or the Golgi apparatus is able to interact with target‐SNARE (t‐SNARE) protein in the plasma membrane following membrane fusion, homologous cell membrane‐coated particles may exhibit certain affinity toward the ER‐Golgi network. L. Chen et al (2022) designed homologous cancer cell membrane‐camouflaged nanoparticles (HCC@NPs). Compared with red blood cell‐coated nanoparticles (RBC@NPs) and PEG‐modified nanoparticles (PEG‐NPs), HCC@NPs specifically targeted the homologous B16‐F10 tumor microenvironment, which was subsequently internalized by tumor cells and selectively accumulated in the ER and ER–Golgi compartment.…”

Section: Endoplasmic Reticulum: the Protein And Lipid Production Factorymentioning

confidence: 99%

Subcellular delivery of lipid nanoparticles to endoplasmic reticulum and mitochondria

Shi

Luo

You

2022

WIREs Nanomed Nanobiotechnol

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Primarily responsible for the biogenesis and metabolism of biomolecules, endoplasmic reticulum (ER) and mitochondria are gradually becoming the targets of therapeutic modulation, whose physiological activities and pathological manifestations determine the functional capacity and even the survival of cells. Drug delivery systems with specific physicochemical properties (passive targeting), or modified by small molecular compounds, polypeptides, and biomembranes demonstrating tropism for ER and mitochondria (active targeting) are able to reduce the nonselective accumulation of drugs, enhancing efficacy while reducing side effects. Lipid nanoparticles feature high biocompatibility, diverse cargo loading, and flexible structure modification, which are frequently used for subcellular organelle‐targeted delivery of therapeutics. However, there is still a lack of systematic understanding of lipid nanoparticle‐based ER and mitochondria targeting. Herein, we review the pathological significance of drug selectively delivered to the ER and mitochondria. We also summarize the molecular basis and application prospects of lipid nanoparticle‐based ER and mitochondria targeting strategies, which may provide guidance for the prevention and treatment of associated diseases and disorders. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Biology‐Inspired Nanomaterials > Lipid‐Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Exocytosis blockade of endoplasmic reticulum-targeted nanoparticle enhances immunotherapy

Cited by 22 publications

References 49 publications

Small-Molecule PROTACs for Cancer Immunotherapy

Small-Molecule PROTACs for Cancer Immunotherapy

Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology

Subcellular delivery of lipid nanoparticles to endoplasmic reticulum and mitochondria

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