Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy

Xu, Xiaoding; Wu, Jun; Liu, Yanlan; Saw, Phei Er; Tao, Wei; Yu, Mikyung; Zope, Harshal; Si, Michelle; Victorious, Amanda; Rasmussen, Jonathan; Ayyash, Dana; Farokhzad, Omid C.; Shi, Jinjun

doi:10.1021/acsnano.6b07195

Cited by 180 publications

(146 citation statements)

References 54 publications

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“…55 In addition, the positively charged polyarginine segments also contribute to the increased siRNA uptake and can simultaneously penetrate the endosomal membranes to improve cytosolic siRNA delivery. 32, 56, 57 …”

Section: Resultsmentioning

confidence: 99%

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy

et al. 2017

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While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core. When the rationally designed, long circulating polymeric NPs accumulate in tumor tissues after intravenous administration, the targeted siRNA-TCPA complexes can be rapidly released via TME pH-mediated NP disassembly for subsequent specific targeting of tumor cells and cytosolic transport, thus achieving efficient gene silencing. In vivo results further demonstrate that the multistaged NP delivery of siRNA against bromodomain 4 (BRD4), a recently discovered target protein that regulates the development and progression of prostate cancer (PCa), can significantly inhibit PCa tumor growth.

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Section: Resultsmentioning

confidence: 99%

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy

et al. 2017

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“…ACUPA has recently been employed for PSMA‐targeted delivery of siRNA to prostate cancer cells. For example, Xu et al developed a nanocarrier comprised of a pH‐responsive polymer blend coated with PEG‐ACUPA for PSMA targeting ( Figure ) . This delivery vehicle was used to deliver siRNA targeting prohibitin 1 (PHB1), which is overexpressed in prostate cancer .…”

Section: Tumor Targetingmentioning

confidence: 99%

“…For example, Xu et al developed a nanocarrier comprised of a pH‐responsive polymer blend coated with PEG‐ACUPA for PSMA targeting ( Figure ) . This delivery vehicle was used to deliver siRNA targeting prohibitin 1 (PHB1), which is overexpressed in prostate cancer . Briefly, nanoparticles extravasate through leaky tumor vasculature and associate specifically with prostate cancer cells via interactions between ACUPA and PSMA.…”

Section: Tumor Targetingmentioning

confidence: 99%

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

2019

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Nucleic acids are a promising type of therapeutic for the treatment of a wide range of conditions, including cancer, but they also pose many delivery challenges. For efficient and safe delivery to cancer cells, nucleic acids must generally be packaged into a vehicle, such as a nanoparticle, that will allow them to be taken up by the target cells and then released in the appropriate cellular compartment to function. As with other types of therapeutics, delivery vehicles for nucleic acids must also be designed to avoid unwanted side effects; thus, the ability of such carriers to target their cargo to cancer cells is crucial. Classes of nucleic acids, hurdles that must be overcome for effective intracellular delivery, types of nonviral nanomaterials used as delivery vehicles, and the different strategies that can be employed to target nucleic acid delivery specifically to tumor cells are discussed. Additonally, nanoparticle designs that facilitate multiplexed delivery of combinations of nucleic acids are reviewed.

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“…They exhibit complementary advantages of both polymeric and lipid nanoparticles. Our group has developed various kinds of LPNs for systemic RNAi and cancer therapy [125, 126]. Similar platforms are being developed for the delivery of tumor suppressor encoding mRNA for cancer therapy [127].…”

Section: Nanotechnology Platforms For Mrna Deliverymentioning

confidence: 99%

Biomedical applications of mRNA nanomedicine

et al. 2018

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As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.

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Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy

Cited by 180 publications

References 54 publications

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy

Cancer‐Targeting Nanoparticles for Combinatorial Nucleic Acid Delivery

Biomedical applications of mRNA nanomedicine

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