Poly(l-cysteine) Peptide Amphiphile Derivatives Containing Disulfide Bonds: Synthesis, Self-Assembly-Induced β-Sheet Nanostructures, pH/Reduction Dual Response, and Drug Release

The accumulation of nanotechnology-based drugs has been realized in various ways. However, the concentration of drugs encapsulated by nanomaterials is not equal to the concentration of effective drugs; often, the drugs become effective only when they are released from the nanomaterials as free drugs. This means only when the drugs are rapidly released after the accumulated drug-encapsulating nanomaterials can they truly achieve the purpose of increasing the concentration of drugs in the tumor. Therefore, we herein report a dual-response nano-carrier of glutathione and acid to achieve the rapid release of encapsulated drug and increase the effective drug concentration in the tumor. The nano-carrier was constructed using a dual-responsive amphiphilic copolymer, composed of polyethylene glycol and hydrophobic acetylated dextran and connected by a disulfide bond. In the tumor microenvironment, disulfide bonds could be biodegraded by glutathione that is overexpressed in the tumor, exposing the core of nano-carrier composed of acetylated dextran. Then the acidic environment would induce the deacetylation of acetylated dextran into water-soluble dextran. In this way, the nano-carrier will degrade quickly, realizing the purpose of rapid drug release. The results showed that the drug release rate of dual-responsive nano-carrier was much higher than that of glutathione or acid-responsive nano-carrier alone. Furthermore, both in vitro and in vivo experiments confirmed that dual-responsive nano-carrier possessed more efficient anti-tumor effects. Therefore, we believe that dual-responsive nano-carriers have better clinical application prospects.

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Molecular Design of Peptide Amphiphiles for Controlled Self-Assembly and Drug Release

Journal of Materials Chemistry B ◽

10.1039/d1tb00173f ◽

2021 ◽

Author(s):

Ziqi Liu ◽

Xuan Tang ◽

Feng Feng ◽

Jing Xu ◽

Can Wu ◽

...

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Self Assembly ◽

Molecular Design ◽

Drug Dose ◽

Peptide Amphiphiles ◽

Great Promise ◽

Specific Drug ◽

Peptide Amphiphile ◽

Drug Delivery Applications

Peptide amphiphile-based supramolecular hydrogels hold great promise in drug delivery applications. To cater for specific drug dose in a demanding biomedical scenario, sophisticated design of peptide amphiphile (PA) molecule is...

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Fabrication of pH/Reduction Sensitive Polyethylene Glycol-Based Micelles for Enhanced Intracellular Drug Release

Pharmaceutics ◽

10.3390/pharmaceutics13091464 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1464

Author(s):

Yang Yang ◽

Fuwei Yang ◽

Xiaotian Shan ◽

Jiamin Xu ◽

Wenjie Fang ◽

...

Keyword(s):

Drug Release ◽

Tumor Cells ◽

Disulfide Bonds ◽

Polymeric Micelles ◽

Inhibitory Effect ◽

In Vitro Drug Release ◽

In Vivo Antitumor Activity ◽

Ph Reduction

At present, the drug is still difficult to release completely and quickly only with single stimulation. In order to promote the rapid release of polymeric micelles at tumor site, pH/reduction sensitive polymers (PCT) containing disulfide bonds and orthoester groups were synthesized. The PCT polymers can self-assemble in water and entrap doxorubicin to form drug-loaded micelles (DOX/PCT). In an in vitro drug release experiment, the cumulative release of DOX/PCT micelles in the simulated tumor microenvironment (pH 5.0 with GSH) reached (89.7 ± 11.7)% at 72 h, while it was only (16.7 ± 6.1)% in the normal physiological environment (pH 7.4 without GSH). In addition, pH sensitive DOX loaded micellar system (DOX/PAT) was prepared as a control. Furthermore, compared with DOX/PAT micelles, DOX/PCT micelles showed the stronger cytotoxicity against tumor cells to achieve an effective antitumor effect. After being internalized by clathrin/caveolin-mediated endocytosis and macropinocytosis, DOX/PCT micelles were depolymerized in intercellular acidic and a reductive environment to release DOX rapidly to kill tumor cells. Additionally, DOX/PCT micelles had a better inhibitory effect on tumor growth than DOX/PAT micelles in in vivo antitumor activity studies. Therefore, pH/reduction dual sensitive PCT polymers have great potential to be used as repaid release nanocarriers for intercellular delivery of antitumor drugs.

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Interfacial Crystallization and Supramolecular Self-Assembly of Spider Silk Inspired Protein at the Water-Air Interface

Materials ◽

10.3390/ma14154239 ◽

2021 ◽

Vol 14 (15) ◽

pp. 4239

Author(s):

Pezhman Mohammadi ◽

Fabian Zemke ◽

Wolfgang Wagermaier ◽

Markus B. Linder

Keyword(s):

Self Assembly ◽

Spider Silk ◽

Assembly Process ◽

Protein Solution ◽

Time Resolved ◽

Macromolecular Assembly ◽

X Ray Scattering ◽

Air Interface ◽

Fundamental Research ◽

Β Sheet

Macromolecular assembly into complex morphologies and architectural shapes is an area of fundamental research and technological innovation. In this work, we investigate the self-assembly process of recombinantly produced protein inspired by spider silk (spidroin). To elucidate the first steps of the assembly process, we examined highly concentrated and viscous pendant droplets of this protein in air. We show how the protein self-assembles and crystallizes at the water–air interface into a relatively thick and highly elastic skin. Using time-resolved in situ synchrotron X-ray scattering measurements during the drying process, we showed that the skin evolved to contain a high β-sheet amount over time. We also found that β-sheet formation strongly depended on protein concentration and relative humidity. These had a strong influence not only on the amount, but also on the ordering of these structures during the β-sheet formation process. We also showed how the skin around pendant droplets can serve as a reservoir for attaining liquid–liquid phase separation and coacervation from the dilute protein solution. Essentially, this study shows a new assembly route which could be optimized for the synthesis of new materials from a dilute protein solution and determine the properties of the final products.

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Glycosylation of a Nonfibrillizing Appendage Alters the Self-Assembly Pathway of a Synthetic β-Sheet Fibrillizing Peptide

The Journal of Physical Chemistry B ◽

10.1021/acs.jpcb.1c02083 ◽

2021 ◽

Author(s):

Ran Zuo ◽

Renjie Liu ◽

Juanpablo Olguin ◽

Gregory A. Hudalla

Keyword(s):

Self Assembly ◽

The Self ◽

Assembly Pathway ◽

Β Sheet

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Microenvironment pH-Induced Selective Cell Death for Potential Cancer Therapy Using Nanofibrous Self-Assembly of a Peptide Amphiphile

Biomacromolecules ◽

10.1021/acs.biomac.1c00267 ◽

2021 ◽

Author(s):

Shota Yamamoto ◽

Kanon Nishimura ◽

Kenta Morita ◽

Sayuki Kanemitsu ◽

Yuki Nishida ◽

...

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Self Assembly ◽

Peptide Amphiphile ◽

Potential Cancer ◽

Microenvironment Ph

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Polymerisation-induced self-assembly (PISA) as a straightforward formulation strategy for stimuli-responsive drug delivery systems and biomaterials: recent advances

Biomaterials Science ◽

10.1039/d0bm01406k ◽

2021 ◽

Vol 9 (1) ◽

pp. 38-50

Author(s):

Hien Phan ◽

Vincenzo Taresco ◽

Jacques Penelle ◽

Benoit Couturaud

Keyword(s):

Drug Delivery ◽

Block Copolymers ◽

Drug Release ◽

Self Assembly ◽

Drug Delivery Systems ◽

Amphiphilic Block Copolymers ◽

Stimuli Responsive ◽

Site Specific ◽

On Demand ◽

Redox Agents

Stimuli-responsive amphiphilic block copolymers obtained by PISA have emerged as promising nanocarriers for enhancing site-specific and on-demand drug release in response to a range of stimuli such as pH, redox agents, light or temperature.

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