Lorenzo Berti

The use of inorganic nanoparticles NPs as vectors for the delivery of oligonucleotides for in vitro and in vivo applications is rapidly gaining momentum Some of the reasons making them especially good candidates for this purpose are their ease of synthesis in a range of sizes and surface coatings their propensity to penetrate cell membranes their stability and biocompatibility and their unique size-dependent physical properties that impart additional diagnostic and therapeutic tools Notwithstanding these notable attributes a major obstacle to their practical use is given by the typically low oligonucleotide loading levels attainable through conventional bioconjugation procedures This shortcoming is especially worrisome as toxicity concerns have been associated with codelivery of NPs In this paper we are analytically analyzing the formation of electrostatic complexes between negatively charged ssDNA and positively charged iron oxide nanoparticles SPIO-NP with the purpose of identifying the optimal conditions leading to stable formulations at high oligo loading levels The formation and loading levels of ssDNA SPIO-NP complexes have been investigated at different oligo NP ratios and under different ionic strengths through dynamic light scattering fluorescence quenching experiments and pull-down assays Through these studies we have identified optimal conditions for attaining maximal oligo loading levels and we are proposing a simple model to explain an unusual behavior observed in the formation of the complexes Finally we introduce an alternative loading method relying on the electrostatic coloading of an oligo sequence in the presence of a negatively charged PEGylated block copolymer yielding very stable and high loading PEGylated ssDNA SPIO-NPs The findings that we are reporting are of general validity and similar conditions could be easily translated to the electrostatic formation of ssDNA NP complexes consisting of different NP materials and sizes

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Well-Defined, Reversible Boronate Crosslinked Nanocarriers for Targeted Drug Delivery in Response to Acidic pH Values an...

Maximization of loading and stability of ssDNA:iron oxide nanoparticle complexes formed through electrostatic interactio...

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