New tools for the quantitative assessment of prodrug delivery and XXXX .

@entity1 @entity137 @entity0 @entity5 @entity19 @entity1235 @entity1897 @entity2359
UNASSIGNED: Systemic off-target @entity137 , including @entity2359 , are prevalent side effects in @entity5 @entity1 treated with a number of otherwise highly efficacious anticancer drugs. In the current study, we have: (1) developed a new analytical metric for the in vivo preclinical assessment of systemic @entity137 / @entity2359 of new drugs and delivery systems; and (2) evaluated, in @entity19 , the in vivo efficacy and @entity137 of a versatile and modular NanoDendron (ND) drug delivery and imaging platform that we recently developed. Our paclitaxel-carrying ND prodrug, ND(PXL), is activated following proteolytic cleavage by @entity1235 , resulting in localized cytotoxic chemotherapy. Using click chemistry, we combined ND(PXL) with a traceable beacon, ND(PB), yielding ND(PXL)-ND(PB) that functions as a theranostic compound. In vivo fluorescence FRET imaging of this theranostic platform was used to confirm localized delivery to @entity5 and to assess the efficiency of drug delivery to @entity5 , achieving 25-30% activation in the @entity5 of an immunocompetent @entity19 model of @entity0 . In this model, ND-drug exhibited anti- @entity5 efficacy comparable to nab-paclitaxel, a clinical formulation. In addition, we combined neurobehavioral metrics of nociception and sensorimotor performance of individual @entity19 to develop a novel composite @entity137 score that reveals and quantifies peripheral @entity2359 , a debilitating long-term systemic @entity137 of paclitaxel therapy. Importantly, @entity19 treated with nab-paclitaxel developed changes in behavioral metrics with significantly higher @entity137 scores indicative of @entity1897 , while @entity19 treated with ND(PXL) showed no significant changes in behavioral responses or @entity137 score. Our ND formulation was designed to be readily adaptable to incorporate different drugs, imaging modalities and/or targeting motifs. This formulation has significant potential for preclinical and clinical tools across multiple disease states. The studies presented here report a novel @entity137 score for assessing @entity1897 and demonstrate that our targeted, theranostic NDs are safe and effective, providing localized @entity5 delivery of a chemotherapeutic and with reduced common @entity2359 side-effects.
