2013
DOI: 10.1073/pnas.1309566110
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Abstract: Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20-to 30-nm-diameter, multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and human data from s… Show more

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Cited by 115 publications
(113 citation statements)
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References 40 publications
(113 reference statements)
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“…Studies with liposome nanoparticles suggest that allometric scaling based on body weight works reasonably well (20). However, the AUC of a polymer-based nanoparticle of camptothecin (CRLX101) scaled best across species based on body-surface area (21). Here, we find that allometric scaling across species best correlates with body weight rather than with body-surface area.…”
Section: Mild Dose-dependent Elevations In Serum Cytokines Followingmentioning
confidence: 58%
“…Studies with liposome nanoparticles suggest that allometric scaling based on body weight works reasonably well (20). However, the AUC of a polymer-based nanoparticle of camptothecin (CRLX101) scaled best across species based on body-surface area (21). Here, we find that allometric scaling across species best correlates with body weight rather than with body-surface area.…”
Section: Mild Dose-dependent Elevations In Serum Cytokines Followingmentioning
confidence: 58%
“…The pharmacologically active component of CRLX101-CPT-has intrinsic fluorescence (Excitation max = 370 nm and Emission max = 435 nm), and can be used for the detection of CRLX101 in tissue via fluorescence microscopy (5,6,8). Fig.…”
Section: Resultsmentioning
confidence: 99%
“…CRLX101 first enters mouse model xenografts within 6 h of i.v. administration and slowly diffuses away from blood vessels and deeper into tumors over several days (5). Therefore, the quantity of CPT present in the patient samples 24 h after treatment may strongly depend on location of the biopsy relative to vasculature.…”
Section: Discussionmentioning
confidence: 99%
“…CRLX101 has also been shown to be a radiosensitiser in an animal model of head and neck cancer, suggesting that CRLX101 may achieve clinical utility in combination with radiotherapy. 6,134 It has further been demonstrated in preclinical studies that CRLX101 is a potent and durable inhibitor of HIF-1a. 7,149 The camptothecin family of compounds (including CPT and TPT) have been described as inhibitors of HIF-1a in the past.…”
Section: Resultsmentioning
confidence: 99%
“…This unique feature of CRLX101 grants favourable pharmacokinetics with minimal a toxicity profile (Figure 8.2). 1,133,134 Lactone ring stabilisation is a key feature of CRLX101, since CPT is conjugated to the polymer in such a way as to protect the lactone ring from being opened up. CPT is functionalised to form an ester bond at the 20-hydroxyl group and a glycine linker was used to provide optimal antitumour efficacy with low toxicity.…”
Section: Crlx101 Chemistrymentioning
confidence: 99%