Engineered smart materials for RNA based molecular therapy to treat Glioblastoma

Singh, Ravi Raj; Mondal, Indranil; Janjua, Taskeen; Popat, Amirali; Kulshreshtha, Ritu

doi:10.1016/j.bioactmat.2023.11.007

Cited by 4 publications

(3 citation statements)

References 454 publications

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“…RNA plays a pivotal role in controlling various pathological processes, including those involved in viral replication. As a result, several RNA molecules or their fragments have garnered interest for their potential use as therapeutic targets or as model systems to understand the mechanisms of RNA recognition [ 33 , 34 , 35 , 36 ]. One extensively studied RNA-based model is the trans -activation responsive region (TAR) RNA located at the 5′-end of nascent transcripts of HIV-1, responsible for elongating proviral DNA during integration into the host chromosome.…”

Section: Introductionmentioning

confidence: 99%

Solid Phase Synthesis and TAR RNA-Binding Activity of Nucleopeptides Containing Nucleobases Linked to the Side Chains via 1,4-Linked-1,2,3-triazole

Mucha,

Pieszko,

Bylińska

et al. 2024

Biomedicines

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Nucleopeptides (NPs) represent synthetic polymers created by attaching nucleobases to the side chains of amino acid residues within peptides. These compounds amalgamate the characteristics of peptides and nucleic acids, showcasing a unique ability to recognize RNA structures. In this study, we present the design and synthesis of Fmoc-protected nucleobase amino acids (1,4-TzlNBAs) and a new class of NPs, where canonical nucleobases are affixed to the side chain of L-homoalanine (Hal) through a 1,4-linked-1,2,3-triazole (HalTzl). Fmoc-protected 1,4-TzlNBAs suitable for HalTzl synthesis were obtained via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) conjugation of Fmoc-L-azidohomoalanine (Fmoc-Aha) and N1- or N9-propargylated nucleobases or their derivatives. Following this, two trinucleopeptides, HalTzlAAA and HalTzlAGA, and the hexanucleopeptide HalTzlTCCCAG, designed to complement bulge and outer loop structures of TAR (trans-activation response element) RNA HIV-1, were synthesized using the classical solid-phase peptide synthesis (SPPS) protocol. The binding between HalTzls and fluorescently labeled 5′-(FAM(6))-TAR UCU and UUU mutant was characterized using circular dichroism (CD) and fluorescence spectroscopy. CD results confirmed the binding of HalTzls to TAR RNA, which was evident by a decrease in ellipticity band intensity around 265 nm during complexation. CD thermal denaturation studies indicated a relatively modest effect of complexation on the stability of TAR RNA structure. The binding of HalTzls at an equimolar ratio only marginally increased the melting temperature (Tm) of the TAR RNA structure, with an increment of less than 2 °C in most cases. Fluorescence spectroscopy revealed that HalTzlAAA and HalTzlAGA, complementary to UUU or UCU bulges, respectively, exhibited disparate affinities for the TAR RNA structure (with Kd ≈ 30 and 256 µM, respectively). Hexamer HalTzlTCCCAG, binding to the outer loop of TARUCU, demonstrated a moderate affinity with Kd ≈ 38 µM. This study demonstrates that newly designed HalTzls effectively bind the TAR RNA structure, presenting a potential new class of RNA binders and may be a promising scaffold for the development of a new class of antiviral drugs.

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Section: Introductionmentioning

confidence: 99%

Solid Phase Synthesis and TAR RNA-Binding Activity of Nucleopeptides Containing Nucleobases Linked to the Side Chains via 1,4-Linked-1,2,3-triazole

Mucha,

Pieszko,

Bylińska

et al. 2024

Biomedicines

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“…Glioblastoma (GBM) represents the most prevalent type of cancer in the central nervous system (CNS), constituting nearly 80% of all CNS malignancies. 29,30 Due to the infiltrative growth of GBM, the prognosis of GBM patients is often poor, with a median survival of only 14.6 months, and molecular diagnostic technology for GBM is still lacking. 31,32 Since tumor cells need to maintain intracellular redox homeostasis and protect themselves against reactive oxygen species, the expression of glutathione (GSH) in tumor cells is higher than that in normal cells, making GSH a biomarker for tumor cells.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Glioblastoma (GBM) represents the most prevalent type of cancer in the central nervous system (CNS), constituting nearly 80% of all CNS malignancies. , Due to the infiltrative growth of GBM, the prognosis of GBM patients is often poor, with a median survival of only 14.6 months, and molecular diagnostic technology for GBM is still lacking. , Since tumor cells need to maintain intracellular redox homeostasis and protect themselves against reactive oxygen species, the expression of glutathione (GSH) in tumor cells is higher than that in normal cells, making GSH a biomarker for tumor cells. , In this work, a novel SERS microneedle (DTNB@Au@Ag microneedle) is designed to quantify GSH for the differentiation of GBM tissues. Under optimal conditions, the DTNB@Au@Ag microneedle is able to detect GSH within 12 min in a wide linear range (0.1–15 mM) with a low limit of detection (0.037 mM), which fully meets the requirements for intraoperative GBM molecular diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Rapid Glutathione Analysis with SERS Microneedles for Deep Glioblastoma Tissue Differentiation

Zhang,

You,

Zhang

et al. 2024

Anal. Chem.

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Enhancing X‐Ray Sensitization with Multifunctional Nanoparticles

Liu,

Wu,

Chen

et al. 2024

Small

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In the progression of X‐ray‐based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.

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Engineered smart materials for RNA based molecular therapy to treat Glioblastoma

Cited by 4 publications

References 454 publications

Solid Phase Synthesis and TAR RNA-Binding Activity of Nucleopeptides Containing Nucleobases Linked to the Side Chains via 1,4-Linked-1,2,3-triazole

Solid Phase Synthesis and TAR RNA-Binding Activity of Nucleopeptides Containing Nucleobases Linked to the Side Chains via 1,4-Linked-1,2,3-triazole

Rapid Glutathione Analysis with SERS Microneedles for Deep Glioblastoma Tissue Differentiation

Enhancing X‐Ray Sensitization with Multifunctional Nanoparticles

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