Rational design of self‐assembled mitochondria‐ targeting lytic peptide conjugates with enhanced tumor selectivity

Taking advantage of the addressability and programmability of DNA/DNA non-covalent interactions we report here the rational design of orthogonal DNA-based addressable tiles that self-assemble into polymer-like structures that can be reconfigured and reorganized by external inputs. The different tiles share the same 5-nucleotide sticky ends responsible for self-assembly but are rationally designed to contain a specific regulator-binding domain that can be orthogonally targeted by different DNA regulator strands (activators and inhibitors). We show that by sequentially adding specific activators and inhibitors it is possible to re-organize in a dynamic and reversible way the formed polymer-like structures to display well-defined distributions: homopolymers made of a single tile, random polymers in which different tiles are distributed randomly and block structures in which the tiles are organized in segments.

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Thio‐Bromo “Click” Reaction Derived Polymer–Peptide Conjugates for Their Self‐Assembled Fibrillar Nanostructures

Macromolecular Bioscience ◽

10.1002/mabi.202000048 ◽

2020 ◽

Vol 20 (6) ◽

pp. 2000048 ◽

Cited By ~ 1

Author(s):

Sonu Kumar ◽

Gerd Hause ◽

Wolfgang H. Binder

Keyword(s):

Click Reaction ◽

Peptide Conjugates ◽

Self Assembled

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Abstract 5600: Destruction of prostate cancer cell xenografts by FSH-Lytic peptide conjugates.

10.1158/1538-7445.am2013-5600 ◽

2013 ◽

Author(s):

Sita Aggarwal ◽

Ted Gauthier ◽

Hector Alila ◽

Carola Leuschner ◽

Namrata Karki ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Peptide Conjugates ◽

Lytic Peptide

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The effects of a low therapeutic dose of βCG fragment–lytic peptide conjugates on ovarian function and gonadotropin secretion in ewes: A randomized controlled trial

Reproductive Biology ◽

10.1016/s1642-431x(12)60040-0 ◽

2010 ◽

Vol 10 (3) ◽

pp. 195-213 ◽

Cited By ~ 1

Author(s):

Emily C. Callery ◽

William Hansel ◽

Pawel M. Bartlewski

Keyword(s):

Randomized Controlled Trial ◽

Therapeutic Dose ◽

Ovarian Function ◽

Controlled Trial ◽

Gonadotropin Secretion ◽

Peptide Conjugates ◽

Lytic Peptide ◽

Randomized Controlled

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Simulations of molecular self-assembled monolayers on surfaces: packing structures, formation processes and functions tuned by intermolecular and interfacial interactions

Physical Chemistry Chemical Physics ◽

10.1039/c6cp01049k ◽

2016 ◽

Vol 18 (33) ◽

pp. 22757-22771 ◽

Cited By ~ 13

Author(s):

Jin Wen ◽

Wei Li ◽

Shuang Chen ◽

Jing Ma

Keyword(s):

Rational Design ◽

Self Assembled Monolayers ◽

Formation Processes ◽

Interfacial Interactions ◽

Assembled Monolayers ◽

Self Assembled

Simulations using QM and MM methods guide the rational design of functionalized SAMs on surfaces.

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Trisulfide bond–mediated doxorubicin dimeric prodrug nanoassemblies with high drug loading, high self-assembly stability, and high tumor selectivity

Science Advances ◽

10.1126/sciadv.abc1725 ◽

2020 ◽

Vol 6 (45) ◽

pp. eabc1725

Author(s):

Yinxian Yang ◽

Bingjun Sun ◽

Shiyi Zuo ◽

Ximu Li ◽

Shuang Zhou ◽

...

Keyword(s):

Cancer Therapy ◽

Self Assembly ◽

Rational Design ◽

Colloidal Stability ◽

Drug Loading ◽

High Drug ◽

Tumor Selectivity ◽

Poor Stability ◽

High Drug Loading

Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.

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