Compositions for inhibiting oligonucleotide activity in vitro or in vivo to a cell that are formulated with at least one oligonucleotide encapsulated in a lipid nanoparticle, methods of making, and methods of using the same are disclosed.

Embodiments provide systems, methods, and compositions for nanoparticle-based drug delivery to target cells or tissues. A drug delivery system may include a nanoparticle with a targeting component and a therapeutic component. The nanoparticle may have a predetermined number or valence of targeting molecules for multivalent interaction with a target cell or tissue. Binding of the targeting molecules to the target cell may result in receptor-mediated uptake of the nanoparticle by the target cell. The therapeutic component may be subsequently released within an endocytic vesicle of the target cell. Nanoparticle-based drug delivery systems as described herein may provide improved efficacy and/or reduced toxicity.

The invention concerns compounds of the formula: X(Y).sub.t wherein: X is Formula (X), each Y is the same or different and is Formula (Y) O[CH.sub.2CH(OH)CH.sub.2O].sub.mH; or C(OR.sup.5).sub.3; R.sup.1, R.sup.2, R.sup.3, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10 are each, independently, (CH.sub.2CH.sub.2O).sub.mR.sup.4, [CH.sub.2CH(OH)CH.sub.2O].sub.nH, OR.sup.11, O(CH.sub.2).sub.PR.sup.13, or (CH.sub.2)R.sup.12; each R.sup.4 is independently OR.sup.5 or OH; R.sup.5, R.sup.11 and R.sup.12 are each, independently, H or C.sub.1-C.sub.30 alkyl; R.sup.13 is NH.sub.3.sup.+Cl.sup. or NHBoc; t is an integer from 2 to 6; m, n, and p are each, independently, an integer from 1 to 12; and each q, r, and s is 0 or 1 and the sum of q+r+s is at least 2. ##STR00001##