scholarly journals Poly(2-alkylacrylic acid) polymers deliver molecules to the cytosol by pH-sensitive disruption of endosomal vesicles

2003 ◽  
Vol 372 (1) ◽  
pp. 65-75 ◽  
Author(s):  
Rachel A. JONES ◽  
Charles Y. CHEUNG ◽  
Fiona E. BLACK ◽  
Jasmine K. ZIA ◽  
Patrick S. STAYTON ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Cell ◽  
Rational Design ◽  
Gene Transfection ◽  
Low Ph ◽  
Haemolytic Activity ◽  
Permeability Barrier ◽  
Cultured Human Cells ◽  
Dna Complex ◽  
Endosomal Vesicles

The permeability barrier posed by cell membranes represents a challenge for the delivery of hydrophilic molecules into cells. We previously proposed that poly(2-alkylacrylic acid)s are endocytosed by cells into acidified vesicles and are there triggered by low pH to disrupt membranes and release the contents of endosomes/lysosomes to the cytosol. If this hypothesis is correct, these polymers could be valuable in drug-delivery applications. The present paper reports functional comparisons of a family of three poly(2-alkylacrylic acid)s. Poly(2-propylacrylic acid) (PPAA), poly(2-ethylacrylic acid) (PEAA) and poly(2-methylacrylic acid) (PMAA) were compared in red-blood-cell haemolysis assays and in a lipoplex (liposome–DNA complex) assay. We also directly examined the ability of these polymers to disrupt endosomes and lysosomes in cultured human cells. Our results show that: (i) unlike membrane-disruptive peptides, the endosomal-disruptive ability of poly(2-alkylacrylic acid)s cannot necessarily be predicted from their haemolytic activity at low pH, (ii) PPAA (but not PEAA or PMAA) potently facilitates gene transfection by cationic lipoplexes and (iii) endocytosed poly(2-alkylacrylic acid)s are triggered by luminal acidification to selectively disrupt endosomes (not lysosomes) and release their contents to the cytosol. These results will facilitate the rational design of future endosomal-disrupting polymers for drug delivery.

Advances in the use of MOFs for Cancer Diagnosis and Treatment: An Overview

2020 ◽  
Vol 26 (33) ◽  
pp. 4174-4184
Author(s):  
Marina P. Abuçafy ◽  
Bruna L. da Silva ◽  
João A. Oshiro-Junior ◽  
Eloisa B. Manaia ◽  
Bruna G. Chiari-Andréo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Rational Design ◽  
Gas Adsorption ◽  
Drug Loading ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Academic Community ◽  
Anticancer Drug Delivery ◽  
Diagnostic Agents

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.

Monocyclic Peptides: Types, Synthesis and Applications

2020 ◽  
Vol 22 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Yalda Khazaei-poul ◽  
Shohreh Farhadi ◽  
Sepideh Ghani ◽  
Safar Ali Ahmadizad ◽  
Javad Ranjbari
Keyword(s):  
Drug Delivery ◽  
Cyclic Peptides ◽  
Rational Design ◽  
Bioactive Molecules ◽  
Synthesis Methods ◽  
Targeted Therapeutics ◽  
Diagnostic Agents ◽  
Linear Types ◽  
Microbial Agents ◽  
Structural Classes

: Peptides are considered to be appropriate tools in various biological fields. They can be primarily used for the rational design of bioactive molecules. They can act as ligands in the development of targeted therapeutics as well as diagnostics, can be used in the design of vaccines or can be employed in agriculture. Peptides can be classified in two broad structural classes: linear and cyclic peptides. Monocyclic peptides are a class of polypeptides with one macrocyclic ring that bears advantages, such as more selective binding and uptake by the target receptor, as well as higher potency and stability compared to linear types. This paper provides an overview of the categories, synthesis methods and various applications of cyclic peptides. The various applications of cyclic peptides include their use as pro-apoptotic and anti-microbial agents, their application as targeting ligands in drug delivery and diagnostic agents, as well as agricultural and therapeutics applications that are elaborated and discussed in this paper.

scholarly journals A cookbook for DNase Hi-C

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria Gridina ◽  
Evgeniy Mozheiko ◽  
Emil Valeev ◽  
Ludmila P. Nazarenko ◽  
Maria E. Lopatkina ◽  
...  
Keyword(s):  
Rational Design ◽  
Restriction Enzymes ◽  
Nucleotide Exchange ◽  
Computational Tools ◽  
3 Dimensional ◽  
Cultured Human Cells ◽  
Dna Ends ◽  
By Products ◽  
Robust Protocol

Abstract Background The Hi-C technique is widely employed to study the 3-dimensional chromatin architecture and to assemble genomes. The conventional in situ Hi-C protocol employs restriction enzymes to digest chromatin, which results in nonuniform genomic coverage. Using sequence-agnostic restriction enzymes, such as DNAse I, could help to overcome this limitation. Results In this study, we compare different DNAse Hi-C protocols and identify the critical steps that significantly affect the efficiency of the protocol. In particular, we show that the SDS quenching strategy strongly affects subsequent chromatin digestion. The presence of biotinylated oligonucleotide adapters may lead to ligase reaction by-products, which can be avoided by rational design of the adapter sequences. Moreover, the use of nucleotide-exchange enzymes for biotin fill-in enables simultaneous labelling and repair of DNA ends, similar to the conventional Hi-C protocol. These improvements simplify the protocol, making it less expensive and time-consuming. Conclusions We propose a new robust protocol for the preparation of DNAse Hi-C libraries from cultured human cells and blood samples supplemented with experimental controls and computational tools for the evaluation of library quality.

scholarly journals Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

2022 ◽  
Vol 23 (2) ◽  
pp. 915
Author(s):  
Sofia Gabellone ◽  
Davide Piccinino ◽  
Silvia Filippi ◽  
Tiziana Castrignanò ◽  
Claudio Zippilli ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Molecular Docking ◽  
Controlled Release ◽  
Selectivity Index ◽  
Docking Analysis ◽  
Topoisomerase 1 ◽  
Thymine Dimers ◽  
Repair Pathways ◽  
Dna Complex ◽  
Molecular Docking Analysis

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

Rational design of hollow mesoporous titania nanoparticles loaded with curcumin for UV-controlled release and targeted drug delivery

2021 ◽  
Vol 32 (20) ◽  
pp. 205604
Author(s):  
Zhuoxian Mai ◽  
Jiali Chen ◽  
Qingyun Cao ◽  
Yang Hu ◽  
Xianming Dong ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Targeted Drug Delivery ◽  
Rational Design ◽  
Titania Nanoparticles ◽  
Mesoporous Titania ◽  
Targeted Drug

scholarly journals Rational design of drug delivery systems for potential programmable drug release and improved therapeutic effect

2019 ◽  
Vol 3 (6) ◽  
pp. 1159-1167 ◽  
Author(s):  
Yuxun Ding ◽  
Jinjian Liu ◽  
Xue Li ◽  
Linlin Xu ◽  
Chang Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Release ◽  
Therapeutic Effect ◽  
Drug Delivery Systems ◽  
Rational Design ◽  
Delivery Systems ◽  
Dual Responsive ◽  
Ph Reduction

pH-Reduction dual responsive nanocarriers (DRNs) achieve programmable release of CA4 and CDDP in cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document