Charge of Nanoparticles

Nanoparticle charge has been shown to be important for regulating its pharmacokinetic properties. For example, it has been shown that anionic and cationic liposomes activate the complement system through distinct pathways, suggesting that particle charge may impact particle opsonization and phagocytosis.104 Cationic charge on liposomes has also been shown to reduce their circulating halflife in blood and to affect their biodistribution between the tumor microvasculature and interstitium without impacting overall tumor uptake.105 Nanoparticles could be synthesized with charged surfaces either by using charged polymers, such as poly-L-lysine, polyethylenimine (PEI), or polysaccharides, or through surface modification approaches. For example, the layer-by-layer deposition of ionic polymers have been used to change surface properties of nanoparticles, such as quantum dots, by depositing ionic polymers of interest on the charged nanoparticle surfaces.106 Furthermore, surface charge of nanoparticles has been shown to regulate their biodistribution.107 For example, increasing the charge of cationic pegylated liposomes decreases their accumulation in the spleen and blood while increasing their uptake by the liver and an increasing in the accumulation of liposomes in tumor vessels.105 These experiments suggest that optimizing surface physicochemical properties of nanoparticles to better match the biochemical and physiological features of tumors may enhance the intratumoral delivery of nanoparticles for systemic therapeutic approaches.

For conjugation of the negatively charged aptamers to nanoparticles, the surface charge of the nanoparticle may be important. For example, we believe that direct immobilization of aptamers on cationic nanoparticles made from PEI may result in formation of aptamer-PEI complex that render the aptamer ineffective as a targeting molecule (unpublished observation). Therefore, neutral polymers such as PLA, PLGA or those with a more negative charge, such as polyanhyrides, may be most suitable for conjugation to aptamers. We have used PLA-PEG block copolymers to generate aptamer-nanoparticles bioconjugates.23,108 One approach that may facilitate the use of a wider array of biomaterials for aptamer targeted drug delivery is through methods of "masking" the surface charge of the particles. For example, the addition of neutrally charged hydrophilic layer of PEG on the surface of the nanoparticles may facilitate the use of positively charged materials for the synthesis of nanoparticles. These cationic nanoparticles are particularly useful for gene delivery applications and thus may enable efficient targeted gene delivery using aptamers.

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