Drugging solid tumors with small interfering RNA and rational combinations of molecularly targeted therapeutics can be difficult to achieve using traditional pharmaceutical excipients and drug carriers. Self-assembled polymer nanoparticles represent a powerful tool that can tailor the delivery of a specific drug or drug combination in a manner that maximizes synergistic or synthetic lethal interactions while minimizing toxicity. Here, we describe the development of a hierarchically-assembled polymer drug carrier that targets solid tumors through three independent mechanisms and its use to drug breast tumor xenografts through synergistic horizontal blockade of oncogene-addicted and resistance-associated cell signaling. We also describe the development of a series of lipid-like polypeptides that can be used to deliver small interfering RNA against a novel DNA damage signal effector whose loss is synthetic lethal in the absence of functional tumor suppressor protein p53. These strategies directly address unmet needs in current clinical therapies for breast, lung, and ovarian cancer.

Self-assembled polymer drug carriers for rational combination and RNA interference therapy of solid tumors

248th National Meeting (2014)

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