Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction DOI Open Access
Kristina Klabenkova,

Alyona Zakhryamina,

Е. А. Буракова

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 300 - 300

Published: Dec. 31, 2024

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree biological stability oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by chemical modification internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previously developed a strategy via Staudinger reaction on solid phase intermediate dinucleoside phosphite triester range of, preferably, electron deficient organic azides such sulfonyl during automated solid-phase DNA synthesis according to conventional β-cyanoethyl phosphoramidite scheme. Polyfluoro compounds are characterized unique properties that prompted extensive application both industry scientific research. We report herein isolation novel oligodeoxyribonucleotides incorporating perfluoro-1-octanesulfonyl phosphoramidate or 2,2,2-trifluoroethanesulfonyl groups. In addition, with fluorinated zwitterionic mimics were synthesized tandem methodology, involved (a) introduction carboxylic ester position methyl 2,2-difluoro-3-azidosulfonylacetate; (b) treatment an aliphatic diamine, e.g., 1,1-dimethylethylenediamine 1,3-diaminopropane. It was further shown polyfluoro oligonucleotides obtained able form complementary duplexes either RNA, not significantly differing from natural counterparts. Long-chain perfluoroalkyl taken up into cultured human cells absence transfection agent. concluded described here represent useful platform designing therapeutics.

Language: Английский

Intrinsically Pro‐Apoptotic Gold Nanoclusters for Optical Tracing and Inhibition of Solid Tumors DOI Open Access
Priyanka Sharma, Hao Yuan, Ruchi Verma

et al.

Advanced Healthcare Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract Intrinsically theranostic metal nanoclusters are rare unless the stabilizing ligands exhibit therapeutic properties. A promising class of quasi‐molecular, near‐infrared (NIR) emitting, cytotoxic gold nanoclusters, coined as AXE (Au eXcitable and Eliminable) stabilized through terminal thioester groups on fluorinated, crosslinked polymers, is presented for simultaneous bioimaging & therapy. Nano Variable Temperature‐Electrospray ionization mass spectrometry analysis these aqueous stable revealed 5 to 7 core atoms, with SAXS measurement confirming average size be under 1 nm, consistent theoretical maximum few atom planar clusters. Despite its small size, exhibits a remarkable Stoke shift ≈470 nm emission range spanning 700 1100 nm. Fluorination notably enhanced quantum yield by up twofold, attributed charge transfer from fluorinated monomer core, indicated Löwdin distribution analysis. The nanocluster demonstrated dose‐dependent pro‐apoptotic effects cancer cells while sparing normal at lower concentrations. Preclinical evaluation in breast tumor model confirmed anticancer efficacy, intravenous intraperitoneal administrations significantly inhibiting growth controlling lung metastasis, surpassing clinical standard, doxorubicin.

Language: Английский

Citations

0
Development and Preclinical Evaluation of 18F-Labeled PEGylated Sansalvamide A Decapeptide for Noninvasive Evaluation of Hsp90 Status in Pancreas Cancer DOI
Xiaohui Wang,

Zhijian Han,

Jun Zhang

et al.

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(10), P. 5238 - 5246

Published: Sept. 24, 2024

Heat shock protein 90 (Hsp90) is a promising target for cancer therapy and imaging. Accurate detection of Hsp90 levels in tumors via noninvasive PET imaging might be beneficial management. To achieve this, the precursor compound Dimer-Sansalvamide A (Dimer-San A) was PEGylated modified by conjugating it with bifunctional chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The

Language: Английский

Citations

1
Nanocarriers for intracellular delivery of proteins in biomedical applications: strategies and recent advances DOI Creative Commons
Chuanda Zhu, Jing Mu, Ling Liang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Nov. 10, 2024

Protein drugs are of great importance in maintaining the normal functioning living organisms. Indeed, they have been instrumental combating tumors and genetic diseases for decades. Among these pharmaceutical agents, those that target intracellular components necessitate use therapeutic proteins to exert their effects within targeted cells. However, protein is limited by short half-life potential adverse physiological environment. The advent nanoparticles offers a promising avenue prolonging drugs. This achieved encapsulating proteins, thereby safeguarding biological activity ensuring precise delivery into nanomaterial-based drug system mitigates rapid hydrolysis unwarranted diffusion minimizing side circumventing limitations inherent traditional techniques like electroporation. review examines established systems, including based on polymers, liposomes, nanoparticles. We delve operational principles transport mechanisms nanocarriers, discussing various considerations essential designing cutting-edge platforms. Additionally, we investigate innovative designs applications cytosolic systems medical research clinical practice, particularly areas tumor treatment, gene editing fluorescence imaging. sheds light current restrictions anticipates future avenues, aiming foster continued advancement this field.

Language: Английский

Citations

1
Detection of Tn-antigen in breast and prostate cancer models by VVL-labeled red dye-doped nanoparticles DOI Creative Commons
Alejandra Verhassel, Martha Kimani, Kamlesh Gidwani

et al.

Nanomedicine, Journal Year: 2024, Volume and Issue: 19(29), P. 2463 - 2478

Published: Oct. 9, 2024

Aim: Fluorescence detection of breast and prostate cancer cells expressing Tn-antigen, a tumor marker, with Vicia villosa lectin (VVL)-labeled nanoparticles.

Language: Английский

Citations

0
Synthesis of New Polyfluoro Oligonucleotides via Staudinger Reaction DOI Open Access
Kristina Klabenkova,

Alyona Zakhryamina,

Е. А. Буракова

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 300 - 300

Published: Dec. 31, 2024

Nowadays, nucleic acid derivatives capable of modulating gene expression at the RNA level have gained widespread recognition as promising therapeutic agents. A suitable degree biological stability oligonucleotide therapeutics is required for in vivo application; this can be most expeditiously achieved by chemical modification internucleotidic phosphate group, which may also affect their cellular uptake, tissue distribution and pharmacokinetics. Our group has previously developed a strategy via Staudinger reaction on solid phase intermediate dinucleoside phosphite triester range of, preferably, electron deficient organic azides such sulfonyl during automated solid-phase DNA synthesis according to conventional β-cyanoethyl phosphoramidite scheme. Polyfluoro compounds are characterized unique properties that prompted extensive application both industry scientific research. We report herein isolation novel oligodeoxyribonucleotides incorporating perfluoro-1-octanesulfonyl phosphoramidate or 2,2,2-trifluoroethanesulfonyl groups. In addition, with fluorinated zwitterionic mimics were synthesized tandem methodology, involved (a) introduction carboxylic ester position methyl 2,2-difluoro-3-azidosulfonylacetate; (b) treatment an aliphatic diamine, e.g., 1,1-dimethylethylenediamine 1,3-diaminopropane. It was further shown polyfluoro oligonucleotides obtained able form complementary duplexes either RNA, not significantly differing from natural counterparts. Long-chain perfluoroalkyl taken up into cultured human cells absence transfection agent. concluded described here represent useful platform designing therapeutics.

Language: Английский

Citations

0