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Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled in Silico-Experimental Studies. Part II: Self-Assembled siRNA Nanocarriers

Molecular Biology and Nanotechnology Laboratory ([email protected]), Department of Engineering and Architecture, University of Trieste, 34127 Trieste, Italy
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Pharmaceutics 2019, 11(7), 324; https://doi.org/10.3390/pharmaceutics11070324
Received: 21 June 2019 / Revised: 5 July 2019 / Accepted: 8 July 2019 / Published: 10 July 2019
(This article belongs to the Special Issue Drug Delivery of siRNA Therapeutics)
In part I of this review, the authors showed how poly(amidoamine) (PAMAM)-based dendrimers can be considered as promising delivering platforms for siRNA therapeutics. This is by virtue of their precise and unique multivalent molecular architecture, characterized by uniform branching units and a plethora of surface groups amenable to effective siRNA binding and delivery to e.g., cancer cells. However, the successful clinical translation of dendrimer-based nanovectors requires considerable amounts of good manufacturing practice (GMP) compounds in order to conform to the guidelines recommended by the relevant authorizing agencies. Large-scale GMP-standard high-generation dendrimer production is technically very challenging. Therefore, in this second part of the review, the authors present the development of PAMAM-based amphiphilic dendrons, that are able to auto-organize themselves into nanosized micelles which ultimately outperform their covalent dendrimer counterparts in in vitro and in vivo gene silencing. View Full-Text
Keywords: RNAi therapeutics; siRNA delivery; amphiphilic dendrons; PAMAM dendrimers; self-assembling; nanovectors; gene silencing RNAi therapeutics; siRNA delivery; amphiphilic dendrons; PAMAM dendrimers; self-assembling; nanovectors; gene silencing
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Laurini, E.; Marson, D.; Aulic, S.; Fermeglia, M.; Pricl, S. Evolution from Covalent to Self-Assembled PAMAM-Based Dendrimers as Nanovectors for siRNA Delivery in Cancer by Coupled in Silico-Experimental Studies. Part II: Self-Assembled siRNA Nanocarriers. Pharmaceutics 2019, 11, 324.

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