2014
DOI: 10.1038/mt.2014.27
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Abstract: Ongoing clinical trials target the aberrant PI3K/Akt/mammalian target of rapamycin (mTOR) pathway in breast cancer through administration of rapamycin, an allosteric mTOR inhibitor, in combination with paclitaxel. However, synergy may not be fully exploited clinically because of distinct pharmacokinetic parameters of drugs. This study explores the synergistic potential of site-specific, colocalized delivery of rapamycin and paclitaxel through nanoparticle incorporation. Nanoparticle drug loading was accurately… Show more

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Cited by 58 publications
(51 citation statements)
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“…In a Phase I/II trial involving patients with locally advanced or metastatic breast cancer, non-PEGylated liposomal doxorubicin was administered with trastuzumab and paclitaxel, after which the response rate was found to be 98.1% with a median time to progression of 22.1 months in metastatic patients [52]. Another nanoparticle platform is found in the work of Ferrari et al [53]. They examined the therapeutic potential of delivering rapamycin and paclitaxel preferentially to breast tumors using nanoparticles.…”
Section: Discussionmentioning
confidence: 99%
“…In a Phase I/II trial involving patients with locally advanced or metastatic breast cancer, non-PEGylated liposomal doxorubicin was administered with trastuzumab and paclitaxel, after which the response rate was found to be 98.1% with a median time to progression of 22.1 months in metastatic patients [52]. Another nanoparticle platform is found in the work of Ferrari et al [53]. They examined the therapeutic potential of delivering rapamycin and paclitaxel preferentially to breast tumors using nanoparticles.…”
Section: Discussionmentioning
confidence: 99%
“…This favorable response, however, came at the expense of greater toxicity, resulting in a 2.0-fold increased prevalence of dose-limiting toxicity and a 3.0-fold increased prevalence of drug-related grade >3 adverse events (45). Nanoscale drug formulations such as Abraxane and Doxil can enhance therapeutic index in patients (5) and improve treatments outcomes in combination delivery approaches (6, 9, 12, 14). Previously, we demonstrated that an emerging class of nanoscale drug carrier, LbL nanoparticles, could improve tumor accumulation 4.0-fold and decrease liver accumulation 2.0-fold (24).…”
Section: Discussionmentioning
confidence: 99%
“…While initially proposed to exploit nonoverlapping toxicity profiles of cytotoxic chemotherapeutics, recent advances in cancer cell signaling and the discovery of potent and selective small-molecule inhibitors have led to the development of rational combination approaches to cancer chemotherapy. These strategies can prime cancer cells for apoptosis (3, 4), abrogate mechanisms for resistance (59), block cancer cell-cycle progression (10), or dynamically rewire DNA damage response pathways (11, 12)—all leading to enhanced tumor cell killing.…”
Section: Introductionmentioning
confidence: 99%
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“…Of course, endorsing composite replacements of naturally composite boney tissues comes at the cost of a pervasive concern that an undesirable synergy among the multiple particle components might be produced, the reason for which natural medicines have been traditionally disfavored over monomolecular synthetics. Such synergies resemble double-edged swords in a sense that they could be positive, as in the case when the delivery of clindamycin with CAP nanoparticles canceled out the negative effect that the administration of the pure antibiotic had on the osteogenesis of the bone tissue 241 or in the case when the co-delivery of rapamycin and paclitaxel using nanoparticulate poly(ethylene glycol)-poly(ε-caprolactone) block copolymers had a greater antitumor efficacy than the delivery of the two drugs alone 242 , but they could also be detrimental, as in the cases when increases in toxicity entailed combination drug therapies 243,244 or when binding of fluorophores caused the unintended deformation of the labeled biomolecules 245 , including even the crystal lattice of CAPs 246 . Whatever the case, synergies are inescapable in composite systems and their protean effects, rising steeply in proportion with the number of interactive components, must be carefully assessed prior to the medical application of their therapeutic carriers.…”
Section: Discussionmentioning
confidence: 99%