Transformable amyloid-beta mimetic peptide amphiphiles for lysosomal disruption in non-small cell lung cancer

Baehr, Christopher M.; Zhang, Lu; Wu, Yi; Domokos, Andras; Xiao, Wenwu; Wang, Lei; Lam, Kit S.

doi:10.1016/j.biomaterials.2021.121078

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…However, obvious lysosomal aberrations were observed in Nap – CPT – HCQ – Yp –treated 4T1 cells. It was reported that nanofiber formation could induce lysosomal disruption. , Therefore, after Nap – CPT – HCQ – Yp was catalyzed by ALP and hydrolyzed by CES sequentially, the formed nanofiber Nap – Y – NF could destroy lysosomal structures and, therefore, promote the escape of Nap – CPT – HCQ – Yp from lysosomes. Next, to trace the endocytosis pathway of Nap – CPT – HCQ – Yp , cells were pretreated with l -phenylalanine ( l -Phe, an ALP inhibitor), genistein (an inhibitor of caveolae-mediated endocytosis), chlorpromazine hydrochloride (CPZ, an inhibitor of clathrin-mediated endocytosis), 5-( N , N -dimethyl)-amiloride hydrochloride (amiloride, an inhibitor of macropinocytosis), or under 4 °C (inhibition of adenosine triphosphate (ATP)-related endocytosis) for 2 h. The fluorescence intensity of the cells under the pretreatment of 4 °C, l -Phe, or genistein dropped to 15.5, 31.6, or 29.7% of that of the cells in the PBS group, respectively (Figure a,b).…”

Section: Resultsmentioning

confidence: 99%

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis

et al. 2022

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Metastasis-induced high mortality of cancers urgently demands new approaches to simultaneously inhibit primary tumor metastasis and distant tumor growth. Herein, by rational design of a trident molecule Nap–Phe–Phe–Lys(SA-CPT)–Lys(SA-HCQ)–Tyr(H2PO3)–OH (Nap–CPT–HCQ–Yp) with three functional “spears” (i.e., a phosphotyrosine motif for enzymatic self-assembly, camptothecin (CPT) motif for chemotherapy, and hydroxychloroquine (HCQ) motif for autophagy inhibition) and nanobrush–nanoparticle–nanofiber transition property, we propose a novel strategy of intracellular enzymatic nanofiber formation and synergistic autophagy inhibition-enhanced chemotherapy and immunotherapy for spatial suppression of tumor metastasis. Under sequential alkaline phosphatase catalysis and carboxylesterase hydrolysis, Nap–CPT–HCQ–Yp undergoes nanobrush–nanoparticle–nanofiber transition, accompanied by the releases of CPT and HCQ. The formed intracellular nanofibers effectively inhibit the metastasis and invasion behaviors of cancer cells. Meanwhile, the released CPT and HCQ synergistically induce a prominent therapeutic effect through autophagy inhibition-enhanced chemotherapy. Furthermore, chemotherapy of Nap–CPT–HCQ–Yp enhances immunogenic cell death, resulting in the activation of toxic T-cells. Finally, a combination of checkpoint blockade therapy and Nap–CPT–HCQ–Yp-mediated chemotherapy elicits systemic antitumor immunity, thereby achieving efficient inhibitions of primary tumors as well as distant tumors in a breast tumor model. Our work offers a simple and feasible strategy for the design of “smart” multifunctional prodrugs to spatially suppress tumor metastasis.

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Section: Resultsmentioning

confidence: 99%

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis

et al. 2022

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“…However, 10 μM MQIO-P without light does not have the same effects. According to a quantitative method of isoboles, 64 we established a combination dose isobologram (Figure 8). We can clearly see that the combination index is determined to be 0.293 at 10 μM MQIO-P (with light), and the combination index is the lowest among all the concentrations.…”

Section: Resultsmentioning

confidence: 99%

Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions

et al. 2022

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Controlled self-assembly has attracted extensive interest in biological and nanotechnological applications. Enzymatic or biocatalytic triggered self-assembly is widely used for the diagnostic and prognostic marker in different pathologies because of their nanostructures and biological effects. However, it remains a great challenge to control the self-assembly of peptides in living cells with a high degree of spatial and temporal precision. Here we demonstrate a lighttriggered platform that enables spatiotemporal control of self-assembly from nanoparticles into nanofibers in living cells through subtle molecular conformational changes and internal H-bonding interactions. The platform contained 3methylene-2-(quinolin-8-yl) isoindolin-1-one, which acts as the light-controlled unit to disrupt the hydrophilic/lipophilic balance through the change of molecular conformation, and a peptide that can be a faster recombinant to assemble via H-bonding interactions. The process has good biocompatibility because it does not involve waste generation or oxygen consumption; moreover, the assembly rate constant was fast and up to 0.17 min −1 . It is applied to the regulation of molecular assembly in living cells. As such, our findings demonstrate that light-triggered controllable assembly can be applied for initiative regulating cellular behaviors in living systems.

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“…134 SAPs transform into nanofibers around organelles through rational design, destroy organelles, and induce cancer cell death. Lam et al 135 reported the peptide (CPTNP) containing all D-amino acids (kffvlk) transformed into nanofibers in lysosome due to the shift in π−π interaction between phenylalanine side chains, and therefore inducing lysosomal membrane permeabilization. Based on these properties, CPTNPs could treat tumors and sensitize tumor cells to cisplatin activity.…”

Section: Smart Saps For Therapymentioning

confidence: 99%

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy

Zhou

et al. 2023

ACS Nano

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Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification and supramolecular self-assembly. Stimuli-responsive peptide nanoparticles, also termed "smart" nanoparticles, capable of conformational and chemical changes in response to stimuli, have emerged as a class of promising materials. These smart nanoparticles find a diverse range of biomedical applications, including drug delivery, diagnostics, and biosensors. Stimuli-responsive systems include external stimuli (such as light, temperature, ultrasound, and magnetic fields) and internal stimuli (such as pH, redox environment, salt concentration, and biomarkers), facilitating the generation of a library of self-assembled biomaterials for biomedical imaging and therapy. Thus, in this review, we mainly focus on peptide-based nanoparticles built by self-assembly strategy and systematically discuss their mechanisms in response to various stimuli. Furthermore, we summarize the diverse range of biomedical applications of peptide-based nanomaterials, including diagnosis and therapy, to demonstrate their potential for medical translation.

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Transformable amyloid-beta mimetic peptide amphiphiles for lysosomal disruption in non-small cell lung cancer

Cited by 16 publications

References 39 publications

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis

Light-Triggered Self-Assembly of Peptide Nanoparticles into Nanofibers in Living Cells through Molecular Conformation Changes and H-Bond Interactions

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy

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