scholarly journals Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhen Luo ◽  
Yujuan Gao ◽  
Zhongyu Duan ◽  
Yu Yi ◽  
Hao Wang
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Recent Progress ◽  
Assembly Systems ◽  
Targeted Cancer Therapy ◽  
Cancer Treatments ◽  
Self Assembling ◽  
Stimuli Response

Mitochondria are well known to serve as the powerhouse for cells and also the initiator for some vital signaling pathways. A variety of diseases are discovered to be associated with the abnormalities of mitochondria, including cancers. Thus, targeting mitochondria and their metabolisms are recognized to be promising for cancer therapy. In recent years, great efforts have been devoted to developing mitochondria-targeted pharmaceuticals, including small molecular drugs, peptides, proteins, and genes, with several molecular drugs and peptides enrolled in clinical trials. Along with the advances of nanotechnology, self-assembled peptide-nanomaterials that integrate the biomarker-targeting, stimuli-response, self-assembly, and therapeutic effect, have been attracted increasing interest in the fields of biotechnology and nanomedicine. Particularly, in situ mitochondria-targeted self-assembling peptides that can assemble on the surface or inside mitochondria have opened another dimension for the mitochondria-targeted cancer therapy. Here, we highlight the recent progress of mitochondria-targeted peptide-nanomaterials, especially those in situ self-assembly systems in mitochondria, and their applications in cancer treatments.

Tandem Molecular Self-assembly for Selective Lung Cancer Therapy with Two Orders of Magnitude Increase in Efficiency

Nanoscale ◽  
2021 ◽  
Author(s):  
Debin Zheng ◽  
Jingfei Liu ◽  
Yinghao Ding ◽  
Limin Xie ◽  
Yingying Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Therapy ◽  
Anticancer Drugs ◽  
Self Assembly ◽  
Therapeutic Efficacy ◽  
Self Assembling ◽  
Lung Cancer Therapy ◽  
Magnitude Increase

In situ self-assembling of prodrug molecules into nanomedicine can elevate the therapeutic efficacy of anticancer medications by enhancing the targeting and enrichment of anticancer drugs at tumor sites. However, the...

scholarly journals A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1092
Author(s):  
Dandan Zhu ◽  
Huanle Zhang ◽  
Yuanzheng Huang ◽  
Baoping Lian ◽  
Chi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Cancer Drug ◽  
Acquired Drug Resistance ◽  
Self Assembling ◽  
Amphiphilic Peptide ◽  
Peptide Dendrimer

Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK2 and AmPD KK2K4). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK2 bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK2K4 bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK2 maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer.

scholarly journals Pharmacophore hybridisation and nanoscale assembly to discover self-delivering lysosomotropic new-chemical entities for cancer therapy

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhao Ma ◽  
Jin Li ◽  
Kai Lin ◽  
Mythili Ramachandran ◽  
Dalin Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Self Assembly ◽  
The Self ◽  
Single Drug ◽  
Drug Nanoparticles ◽  
Lysosomal Dysfunction ◽  
New Chemical Entities ◽  
Autophagy Inhibition

Abstract Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

scholarly journals In situ kinetic measurements of α-synuclein aggregation reveal large population of short-lived oligomers

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245548
Author(s):  
Enrico Zurlo ◽  
Pravin Kumar ◽  
Georg Meisl ◽  
Alexander J. Dear ◽  
Dipro Mondal ◽  
...  
Keyword(s):  
Self Assembly ◽  
Large Population ◽  
Paramagnetic Resonance ◽  
Kinetic Measurements ◽  
Toxic Species ◽  
Self Assembling ◽  
Wide Range ◽  
Electron Paramagnetic

Knowledge of the mechanisms of assembly of amyloid proteins into aggregates is of central importance in building an understanding of neurodegenerative disease. Given that oligomeric intermediates formed during the aggregation reaction are believed to be the major toxic species, methods to track such intermediates are clearly needed. Here we present a method, electron paramagnetic resonance (EPR), by which the amount of intermediates can be measured over the course of the aggregation, directly in the reacting solution, without the need for separation. We use this approach to investigate the aggregation of α-synuclein (αS), a synaptic protein implicated in Parkinson’s disease and find a large population of oligomeric species. Our results show that these are primary oligomers, formed directly from monomeric species, rather than oligomers formed by secondary nucleation processes, and that they are short-lived, the majority of them dissociates rather than converts to fibrils. As demonstrated here, EPR offers the means to detect such short-lived intermediate species directly in situ. As it relies only on the change in size of the detected species, it will be applicable to a wide range of self-assembling systems, making accessible the kinetics of intermediates and thus allowing the determination of their rates of formation and conversion, key processes in the self-assembly reaction.

scholarly journals In Situ One-Pot Synthesis of MOF-Polydopamine Hybrid Nanogels with Enhanced Photothermal Effect for Targeted Cancer Therapy

2018 ◽  
Vol 5 (6) ◽  
pp. 1800287 ◽  
Author(s):  
Dongdong Wang ◽  
Huihui Wu ◽  
Jiajia Zhou ◽  
Pengping Xu ◽  
Changlai Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Photothermal Effect ◽  
Targeted Cancer Therapy ◽  
One Pot ◽  
One Pot Synthesis

Self-Assembly of an Aptamer-Decorated, DNA–Protein Hybrid Nanogel: A Biocompatible Nanocarrier for Targeted Cancer Therapy

2019 ◽  
Vol 2 (12) ◽  
pp. 5227-5234 ◽  
Author(s):  
Hari Veera Prasad Thelu ◽  
Siriki Atchimnaidu ◽  
Devanathan Perumal ◽  
Kaloor S. Harikrishnan ◽  
Shajesh Vijayan ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Self Assembly ◽  
Targeted Cancer Therapy

scholarly journals Bioinspired Photo-Crosslinkable Self-Assembling Peptide with pH-Switchable “On−Off” Luminescence.

2021 ◽  
Author(s):  
Raffaele Pugliese ◽  
Monica Montuori ◽  
Fabrizio Gelain
Keyword(s):  
Self Assembly ◽  
Cross Linking ◽  
Significant Progress ◽  
The Past ◽  
Self Assembling ◽  
Made In

Significant progress has been made in the peptides self-assembly over the past two decades, however the in situ cross-linking of self-assembling peptides yielding to better performing nanomaterials is still in...

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