Targeted Enrichment of Enzyme‐Instructed Assemblies in Cancer Cell Lysosomes Turns Immunologically Cold Tumors Hot

Enzymatic noncovalent synthesis (ENS) exploits enzymatic reactions to produce spatially organized higher-order supramolecular assemblies that modulate cellular processes. While ENS is a general mechanism to create higher-order assemblies of proteins for diverse cellular functions, the exploration of ENS of other bioactive molecules, such as peptides or small organic molecules, is rather limited. Since ENS generates non-diffusive supramolecular assemblies locally, it provides a unique approach to targeting subcellular organelles. In this Review, we highlight the recent progress of the application of ENS of peptide assemblies for targeting subcellular organelles. After a brief introduction of the concept of ENS, we introduce the case of generating artificial filaments by ENS in cell cytosol, then discuss the use of ENS for targeting endoplasmic reticulum, mitochondria, Golgi apparatus, and lysosomes, and finally we describe the targeting of nucleus by ENS. We hope to illustrate the promise of ENS, as a localized molecular process in an open system, for understanding diseases, controlling cell behaviors, and developing new therapeutics.

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“…In another work, Ding et al. reported turning immunologically cold tumors hot by LMP‐induced ENS [24] …”

Section: Targeting Lysosomementioning

confidence: 95%

“…In another work, Ding et al reported turning immunologically cold tumors hot by LMP-induced ENS. [24] 8. Targeting Nucleus Nucleus, which stores the genes of cells and acts as the control center of the cell, probably is the most important subcellular organelle.…”

Section: Targeting Lysosomementioning

confidence: 99%

Enzymatic Noncovalent Synthesis for Targeting Subcellular Organelles

Zhang

Tan

2022

ChemPlusChem

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“…The second strategy ( Ji et al, 2021 ; Wu et al, 2021 ) employs an enzyme-instructed self-assembly (EISA) approach. Alkaline phosphatases are highly expressed on the plasma membrane of many types of cancer cells and have been adopted as ELSA-promoting enzymes to induce LMP by mediating nano-aggregation ( Wang et al, 2016 ; Gao et al, 2020a ).…”

Section: Nano-aggregation-induced Lysosomal Membrane Permeabilizationmentioning

confidence: 99%

“…Py-Yp-Lyso had significantly higher cytotoxicity in Hela cells than in normal cells and inhibited tumor growth to 55.4% of that of control tumors at day 15 following the injection. Similarly, Ji et al ( Ji et al, 2021 ) constructed an LMP trigger called TPE-Py-pYK(TPP)pY, which was composed of three segments: tetraphenylethylene-pyride (TPE-Py) mainly for imaging, pYKpY (pY = phosphotyrosine) for self-assembly, and triphenylphosphine (TPP) for charge regulation and internalization. Treating Hela cells with TPE-Py-pYK(TPP)pY caused lysosomal destruction and high cytotoxicity.…”

Section: Nano-aggregation-induced Lysosomal Membrane Permeabilizationmentioning

confidence: 99%

Nanodrugs Detonate Lysosome Bombs

Xiang

Liu

et al. 2022

Front. Pharmacol.

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Cancer cell lysosomes contain various hydrolases and non-degraded substrates that are corrosive enough to destroy cancer cells. However, many traditional small molecule drugs targeting lysosomes have strong side effects because they cannot effectively differentiate between normal and cancer cells. Most lysosome-based research has focused on inducing mild lysosomal membrane permeabilization (LMP) to release anticancer drugs from lysosomal traps into the cancer cell cytoplasm. In fact, lysosomes are particularly powerful “bombs”. Achieving cancer cell-selective LMP induction may yield high-efficiency anticancer effects and extremely low side effects. Nanodrugs have diverse and combinable properties and can be specifically designed to selectively induce LMP in cancer cells by taking advantage of the differences between cancer cells and normal cells. Although nanodrugs-induced LMP has made great progress recently, related reviews remain rare. Herein, we first comprehensively summarize the advances in nanodrugs-induced LMP. Next, we describe the different nanodrugs-induced LMP strategies, namely nanoparticles aggregation-induced LMP, chemodynamic therapy (CDT)-induced LMP, and magnetic field-induced LMP. Finally, we analyze the prospect of nanodrugs-induced LMP and the challenges to overcome. We believe this review provides a unique perspective and inspiration for designing lysosome-targeting drugs.

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“…Copyright 2021, Elsevier Ltd. d) Schematic illustration of nano-assembles inducing lysosomal membrane permeabilization to evoke ICD for turning cold tumor into hot. Reproduced with permission [58]. Copyright 2021, Wiley-VCH GmbH.…”

mentioning

confidence: 99%

Breaking Immunosuppressive Barriers by Engineered Nanoplatforms for Turning Cold Tumor to Hot

Dong

Huang

Zhou

et al. 2022

Advanced Therapeutics

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Cancer immunotherapy, mainly depending on the immune system, holds enormous potential in treating various cancers and received promising results. However, for most patients, their efficacy is greatly limited by the immunosuppressive barrier in the "cold" tumor microenvironment, resulting in a low response rate in the clinic. Thus, in recent decades, breaking the immunosuppressive barriers by engineered nanoplatforms (ENs) has proved to be a prospective strategy to solve the above issues for enhancing cancer immunotherapy. In this review, the authors summarize the characterizations of diverse immunosuppressive barriers and how ENs break them, focusing on the ENs design, potential modulation targets, and therapeutic strategies. It mainly includes: 1) converting poor immunogenicity by nano-adjuvant, 2) alleviating tumor fibrosis by nanoscavenger, and 3) reducing immunosuppressive factors by nanoregulator. Moreover, perspectives toward future directions and challenges are presented to understand further and accelerate the clinical translation of these ENs.

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Targeted Enrichment of Enzyme‐Instructed Assemblies in Cancer Cell Lysosomes Turns Immunologically Cold Tumors Hot

Cited by 62 publications

References 89 publications

Enzymatic Noncovalent Synthesis for Targeting Subcellular Organelles

Enzymatic Noncovalent Synthesis for Targeting Subcellular Organelles

Nanodrugs Detonate Lysosome Bombs

Breaking Immunosuppressive Barriers by Engineered Nanoplatforms for Turning Cold Tumor to Hot

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