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Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

ABSTRACT: Tumor microenvironment is a significant physical barrier to the effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pretreated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed orthotopic 4T1 breast tumors with a paclitaxel (PTX)-loaded iron-oxide-decorated poly(lactic- co-glycolic acid) nanoparticle (NP) composite (PTX@PINC), which can be quickly concentrated in target tissues with the aid of an external magnet, and monitored its effect on the delivery of subsequently administered NPs. Magnetic resonance imaging and optical whole-body imaging confirmed that PTX@PINC was efficiently delivered to tumors by the external magnet and help loosen the tumors to accommodate subsequently delivered NPs. Consistently, the primed tumors responded to Doxil better than nonprimed tumors. In addition, lung metastasis was significantly reduced in the animals PINC-primed prior to Doxil administration. These results support that PINC combined with magnetophoresis can facilitate the timely management of primary tumors with a favorable secondary effect on metastasis.

SUBMITTER: Park J

PROVIDER: S-EPMC6542733 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

Park Jinho J Park Joonyoung J Castanares Mark A MA Collins David S DS Yeo Yoon Y

Molecular pharmaceutics 20190410 5

Tumor microenvironment is a significant physical barrier to the effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pretreated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed or ...[more]

PMID: 30916974

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Project description:PURPOSE:To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS:We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. RESULTS:The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H. CONCLUSIONS:Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

Dataset Information

Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

Publications

Magnetophoretic Delivery of a Tumor-Priming Agent for Chemotherapy of Metastatic Murine Breast Cancer.

Similar Datasets

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