Open Access
Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment
Zhou J. Deng,Stephen W. Morton,Elana Ben-Akiva,Paula T. Hammond,Erik C. Dreaden,Kevin E. Shopsowitz +5 more
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TLDR
The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs.Abstract:
A single nanoparticle platform has been developed through the modular and controlled layer-by-layer process to codeliver siRNA that knocks down a drug-resistance pathway in tumor cells and a chemotherapy drug to challenge a highly aggressive form of triple-negative breast cancer. Layer-by-layer films were formed on nanoparticles by alternately depositing siRNA and poly-l-arginine; a single bilayer on the nanoparticle surface could effectively load up to 3500 siRNA molecules, and the resulting LbL nanoparticles exhibit an extended serum half-life of 28 h. In animal models, one dose via intravenous administration significantly reduced the target gene expression in the tumors by almost 80%. By generating the siRNA-loaded film atop a doxorubicin-loaded liposome, we identified an effective combination therapy with siRNA targeting multidrug resistance protein 1, which significantly enhanced doxorubicin efficacy by 4 fold in vitro and led to up to an 8-fold decrease in tumor volume compared to the control treatments with no observed toxicity. The results indicate that the use of layer-by-layer films to modify a simple liposomal doxorubicin delivery construct with a synergistic siRNA can lead to significant tumor reduction in the cancers that are otherwise nonresponsive to treatment with Doxil or other common chemotherapy drugs. This approach provides a potential strategy to treat aggressive and resistant cancers, and a modular platform for a broad range of controlled multidrug therapies customizable to the cancer type in a singular nanoparticle delivery system.read more
Citations
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Cancer nanomedicine: progress, challenges and opportunities.
TL;DR: Novel engineering approaches are discussed that capitalize on the growing understanding of tumour biology and nano–bio interactions to develop more effective nanotherapeutics for cancer patients.
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Nanotechnology for Multimodal Synergistic Cancer Therapy
TL;DR: In this review, state-of-the-art studies concerning recent advances in nanotechnology-mediated multimodal synergistic therapy will be systematically discussed, with an emphasis on the construction of multifunctional nanomaterials for realizing bimodal and trimodal synergy therapy.
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Elucidating the Fundamental Mechanisms of Cell Death Triggered by Photothermal Therapy
TL;DR: The intracellular signaling cascades involved in the apoptotic response to PTT using cells harboring photothermal transducing nanoprisms are revealed and photothermally induced apoptosis is discussed as a potential therapeutic pathway.
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Cancer Nanomedicine: From Drug Delivery to Imaging
Edward Kai-Hua Chow,Dean Ho +1 more
TL;DR: How particular materials lend themselves to specific applications, the progress to date in clinical translation of nanomedicine, and promising approaches that may catalyze clinical acceptance of nano are discussed.
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Various methods of gold nanoparticles (GNPs) conjugation to antibodies
Mir Hadi Jazayeri,Mir Hadi Jazayeri,Hamed Amani,Ali Akbar Pourfatollah,Hamidreza Pazoki-Toroudi,Bijan Sedighimoghaddam +5 more
TL;DR: The range of recent studies about covalent and noncovalent modes for conjugation of antibodies to the particle surface that aim to advance gold nanoparticle treatments and diagnostics toward the clinic are reviewed.
References
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Knocking down barriers: advances in siRNA delivery
TL;DR: An update on the progress of RNAi therapeutics is provided and novel synthetic materials for the encapsulation and intracellular delivery of nucleic acids are highlighted.
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CD44 is the principal cell surface receptor for hyaluronate.
TL;DR: In this paper, the authors have created soluble CD44-immunoglobulin fusion proteins and characterized their reactivity with tissue sections and lymph node high endothelial cells in primary culture.
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Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
Cornelia Liedtke,Chafika Mazouni,Kenneth R. Hess,Fabrice Andre,Attila Tordai,Jaime A. Mejia,W. Fraser Symmans,Ana M. Gonzalez-Angulo,Bryan T. Hennessy,Marjorie C. Green,Massimo Cristofanilli,Gabriel N. Hortobagyi,Lajos Pusztai +12 more
TL;DR: Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR have excellent survival, however, patients with RD after neoadjuvant chemotherapy have significantly worse survival if they have TNBC compared with other patients, particularly in the first 3 years.
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Transvascular delivery of small interfering RNA to the central nervous system
Priti Kumar,Haoquan Wu,Jodi L. McBride,Kyeong Eun Jung,Moon Hee Kim,Beverly L. Davidson,Sang-Kyung Lee,Premlata Shankar,N. Manjunath +8 more
TL;DR: RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood–brain barrier and afforded robust protection against fatal viral encephalitis in mice.
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Image-based analysis of lipid nanoparticle–mediated siRNA delivery, intracellular trafficking and endosomal escape
Jerome Gilleron,William Querbes,Anja Zeigerer,Anna Borodovsky,Giovanni Marsico,Undine Schubert,Kevin Manygoats,Sarah Seifert,Cordula Andree,Martin Stöter,Hila Epstein-Barash,Ligang Zhang,Victor Koteliansky,Kevin Fitzgerald,Eugenio Fava,Marc Bickle,Yannis Kalaidzidis,Akin Akinc,Martin Maier,Marino Zerial +19 more
TL;DR: It is estimated that escape of siRNAs from endosomes into the cytosol occurs at low efficiency (1–2%) and only during a limited window of time when the LNPs reside in a specific compartment sharing early and late endosomal characteristics.