Multivalency-assisted membrane-penetrating siRNA delivery sensitizes photothermal ablation via inhibition of tumor glycolysis metabolism

Dang, Juanjuan; Ye, Huan; Li, Yongjuan; Liang, Qiujun; Li, Xudong; Yin, Lichen

doi:10.1016/j.biomaterials.2019.119463

Cited by 74 publications

(42 citation statements)

References 58 publications

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“…Accumulating evidence reveals that knockdown of PKM2 by siRNA triggers apoptosis in a panel of cancer cell lines, and substantially retards xenograft growth [34]. However, there are very few reports concerning the efficient delivery of siRNA against PKM2 to tumor cells via gene delivery systems [35][36][37]. In this work, we designed and synthesized a PEI-based siRNA delivery system by integration biodegradable polylactide (PLA) into branched PEI via a facile method, and utilized PEI-PLA copolymer for effective delivery of siRNA against PKM2 for the first time.…”

Section: Introductionmentioning

confidence: 99%

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

et al. 2020

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Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the biodegradable polylactide (PLA) into the branched PEI by synthesizing a PEI-PLA copolymer via a facile synthetic route. PLA modification significantly improved the cytocompatibility of PEI, PEI-PLA copolymer showed much higher cell viability than PEI as verified in three different human cancer cell lines (HCT116, HepG2 and SKOV3). Interestingly, the PEI-PLA copolymer could effectively bind siRNA targeting PKM2, and the obtained polyplex displayed much higher stability in serum than naked siRNA as determined by agarose gel electrophoresis. Moreover, cellular uptake study demonstrated that PEI-PLA could efficiently deliver the Cy5-labled siRNA into the three tested cancer cell lines, and the transfection efficiency is equivalent to the commercial Lipofectamine® 2000. Finally, it is noteworthy that the polyplex is comparable to Lipo2000 in down-regulating the expression of PKM2 at both mRNA and protein level as measured by q-PCR and western blotting, respectively. Overall, the PEI-PLA copolymer developed in this study has the potential to be developed as a versatile carrier for safe and effective delivery of other nucleic acid-based agents.

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Section: Introductionmentioning

confidence: 99%

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

et al. 2020

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“…Besides employing the Glut inhibitors and GOx, Dang et al exploited a new way to accomplish synergistic cancer starvation therapy/low-temperature PTT. The authors used an siRNA against pyruvate kinase M2 (siPKM2, which is capable of interfering with tumor glycolysis) and ICG to fabricate a novel nanocomplex based on a spherical dendrimer polypeptide (DPP) [ 120 ]. Specifically, amine-terminated polyamidoamine (PAMAM) was utilized as a macroinitiator template to synthesize DPP via controlled ring-opening polymerization (ROP) of N -carboxyanhydride followed by side-chain functionalization with guanidines.…”

Section: Applications Of Low-temperature Pttmentioning

confidence: 99%

Low-Temperature Photothermal Therapy: Strategies and Applications

Duan

2021

Research

147

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Although photothermal therapy (PTT) with the assistance of nanotechnology has been considered as an indispensable strategy in the biomedical field, it still encounters some severe problems that need to be solved. Excessive heat can induce treated cells to develop thermal resistance, and thus, the efficacy of PTT may be dramatically decreased. In the meantime, the uncontrollable diffusion of heat can pose a threat to the surrounding healthy tissues. Recently, low-temperature PTT (also known as mild PTT or mild-temperature PTT) has demonstrated its remarkable capacity of conquering these obstacles and has shown excellent performance in bacterial elimination, wound healing, and cancer treatments. Herein, we summarize the recently proposed strategies for achieving low-temperature PTT based on nanomaterials and introduce the synthesis, characteristics, and applications of these nanoplatforms. Additionally, the combination of PTT and other therapeutic modalities for defeating cancers and the synergistic cancer therapeutic effect of the combined treatments are discussed. Finally, the current limitations and future directions are proposed for inspiring more researchers to make contributions to promoting low-temperature PTT toward more successful preclinical and clinical disease treatments.

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“…Modification of nanoparticles by applying albumin to the outer layer can also improve the stability of nanoparticles [82].…”

Section: Other Strategiesmentioning

confidence: 99%

Assembly strategy of liposome and polymer systems for siRNA delivery

Song

Hart

2021

International Journal of Pharmaceutics

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Multivalency-assisted membrane-penetrating siRNA delivery sensitizes photothermal ablation via inhibition of tumor glycolysis metabolism

Cited by 74 publications

References 58 publications

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery

Low-Temperature Photothermal Therapy: Strategies and Applications

Assembly strategy of liposome and polymer systems for siRNA delivery

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