Designed nucleus penetrating thymine-capped dendrimers: a potential vehicle for intramuscular gene transfection

Yan, Jiaying; Liu, Chia-Yeh; Wu, Zong-Wei; Chien, Chih-Te; Chiu, Wan-Ching; Lin, Shu‐Yi

doi:10.1039/c5tb01435b

Cited by 3 publications

(4 citation statements)

References 34 publications

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“…Of the tested thymine coverages, only the 50% thymine-modified PAMAM promoted both siRNA/pDNA condensation and efficient release of siRNA/pDNA, which is predictive of increased transfection activity. This finding is consistent with previous studies suggesting enhanced gene transfection mediated by the 50% thymine-capped PAMAM dendrimer/pDNA complex (17). Thus, 50% thymine-capped PAMAM dendrimers were used to form the dendrimer/siRNA/pDNA complex at a weight ratio of approximately 2:1:1.…”

Section: Preparation and Characterization Of Tumor-targeted Lipid/ De...supporting

confidence: 92%

“…First, this dendrimer condenses the genetic cargoes (siRNA and pDNA) and increases the stability of the nanoscale nucleic acid-dendrimer-CaP cores. Thymines and primary amines on the thymine-capped dendrimer may synergistically interact with and protect siRNA/ pDNA via electrostatic interaction and hydrogen bonding (17). Second, the dendrimer triggers efficient endosomal escape and intracellular release of genetic cargoes (24), increases pDNA uptake in the nucleus, and induces strong transfection activity.…”

Section: Discussionmentioning

confidence: 99%

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Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer

et al. 2020

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While immunotherapy holds great promise for combating cancer, the limited efficacy due to an immunosuppressive tumor microenvironment and systemic toxicity hinder the broader application of cancer immunotherapy. Here, we report a combinatorial immunotherapy approach that uses a highly efficient and tumor-selective gene carrier to improve anticancer efficacy and circumvent the systemic toxicity. In this study, we engineered tumor-targeted lipid-dendrimer-calcium-phosphate (TT-LDCP) nanoparticles (NPs) with thymine-functionalized dendrimers that exhibit not only enhanced gene delivery capacity but also immune adjuvant properties by activating the stimulator of interferon genes (STING)–cGAS pathway. TT-LDCP NPs delivered siRNA against immune checkpoint ligand PD-L1 and immunostimulatory IL-2–encoding plasmid DNA to hepatocellular carcinoma (HCC), increased tumoral infiltration and activation of CD8+ T cells, augmented the efficacy of cancer vaccine immunotherapy, and suppressed HCC progression. Our work presents nanotechnology-enabled dual delivery of siRNA and plasmid DNA that selectively targets and reprograms the immunosuppressive tumor microenvironment to improve cancer immunotherapy.

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Section: Preparation and Characterization Of Tumor-targeted Lipid/ De...supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer

et al. 2020

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“…For instance, Xu et al (2019) demonstrated that grafting PAMAM dendrimers with guanidinobenzoic acid enhanced binding and endosomal disruption, enabling efficient delivery of various proteins and peptides into the cytosol of living cells. Furthermore, a recent study found that modification of PAMAM dendrimers (i.e., by capping the dendrimers with thymine) can result in several multifunctional immunotherapy characteristics: (1) synergistic interaction with and protection of genetic cargoes (siRNA and pDNA) via electrostatic interaction and hydrogen bonding; (2) enhanced endosomal escape and intracellular release of genetic cargoes; (3) increased pDNA uptake in the nucleus and enhanced gene transfection activity; and (4) enhanced stimulation of prominent immunity-related pathways and promotion of cellular immunity (K.-W. Huang et al, 2020;Yan et al, 2015). However, although many of the PAMAM dendrimerbased vaccines have demonstrated high efficiency and selectivity, their effects are often ephemeral, requiring additional research to be completed to develop nanovaccines with long-term anti-tumor immunity.…”

Section: Vaccinesmentioning

confidence: 99%

“…Specifically for the dendrimer-based vaccine systems, many of the systems developed so far have not yet been optimized for introduction into clinical settings. Several studies have shown that the tested systems were not sufficient to protect individuals from subsequent challenges and only induced ephemeral immunity effects (Daftarian et al, 2011;K.-W. Huang et al, 2020;Yan et al, 2015). Also, regardless of the type of dendrimer, the scaffolds had to undergo additional conjugation with functional groups or be paired with checkpoint inhibitors to ensure successful cancer inhibition (Blankenstein et al, 2012;Horvath et al, 2002;Kumar et al, 1992;Vichier-guerre et al, 2000;Xu et al, 2019).…”

Section: Limitationsmentioning

confidence: 99%

Dendrimers for cancer immunotherapy: Avidity‐based drug delivery vehicles for effective anti‐tumor immune response

Rawding

Wang

et al. 2021

WIREs Nanomed Nanobiotechnol

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Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti‐tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well‐defined architecture. This review offers a comprehensive overview of dendrimer‐based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune‐suppressive responses (immune checkpoint inhibitors). On‐going works and prospects of dendrimer‐based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer‐based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies

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Targeted Drug Delivery Strategies for the Treatment of Hepatocellular Carcinoma

Liu,

Wu,

et al. 2024

Molecules

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Hepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumors, exhibiting a high incidence rate that presents a substantial threat to human health. The use of sorafenib and lenvatinib, commonly employed as single-agent targeted inhibitors, complicates the treatment process due to the absence of definitive targeting. Nevertheless, the advent of nanotechnology has injected new optimism into the domain of liver cancer therapy. Nanocarriers equipped with active targeting or passive targeting mechanisms have demonstrated the capability to deliver drugs to tumor cells with high efficiency. This approach not only facilitates precise delivery to the affected site but also enables targeted drug release, thereby enhancing therapeutic efficacy. As medical technology progresses, there is an increasing call for innovative treatment modalities, including novel chemotherapeutic agents, gene therapy, phototherapy, immunotherapy, and combinatorial treatments for HCC. These emerging therapies are anticipated to yield improved clinical outcomes for patients, while minimizing systemic toxicity and adverse effects. Consequently, the application of nanotechnology is poised to significantly improve HCC treatment. This review focused on targeted strategies for HCC and the application of nanotechnology in this area.

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Designed nucleus penetrating thymine-capped dendrimers: a potential vehicle for intramuscular gene transfection

Abstract: A nucleus penetrating vehicle is indispensible when seeking to deliver plasmid DNA for gene transfection.

Cited by 3 publications

References 34 publications

Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer

Highly efficient and tumor-selective nanoparticles for dual-targeted immunogene therapy against cancer

Dendrimers for cancer immunotherapy: Avidity‐based drug delivery vehicles for effective anti‐tumor immune response

Targeted Drug Delivery Strategies for the Treatment of Hepatocellular Carcinoma

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