Microrobotics for Precision Biofilm Diagnostics and Treatment.

Advances in small-scale robotics and nanotechnology are providing previously unimagined opportunities for new diagnostic and therapeutic approaches with high precision, control, and efficiency. We designed microrobots for tetherless biofilm treatment and retrieval using iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality as building blocks. We show 2 distinct microrobotic platforms. The first system is formed from NPs that assemble into aggregated microswarms under magnetic fields that can be controlled to disrupt and retrieve biofilm samples for microbial analysis. The second platform is composed of 3-dimensional (3D) micromolded opacifier-infused soft helicoids with embedded catalytic-magnetic NPs that can be visualized via existing radiographic imaging techniques and controlled magnetically inside the root canal, uninterrupted by the soft and hard tissues surrounding the teeth in an ex vivo model. These microrobots placed inside the root canal can remove biofilms and be efficiently guided with microscale precision. The proof-of-concept paradigm described here can be adapted to target difficult-to-reach anatomical spaces in other natural and implanted surfaces in an automated and tether-free manner.

A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study).

BACKGROUND: Neoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel leads to an overall pathologic complete response (pCR) rate of 46%. Dual HER2 blockade with ado-trastuzumab emtansine (T-DM1) and lapatinib plus nab-paclitaxel has shown efficacy in patients with metastatic HER2-positive breast cancer. To test neoadjuvant effectiveness of this regimen, an open-label, multicenter, randomized, phase II trial was conducted comparing T-DM1, lapatinib, and nab-paclitaxel with trastuzumab, pertuzumab, and paclitaxel in patients with early-stage HER2-positive breast cancer. METHODS: Stratification by estrogen receptor (ER) status occurred prior to randomization. Patients in the experimental arm received 6 weeks of targeted therapies (T-DM1 and lapatinib) followed by T-DM1 every 3 weeks, lapatinib daily, and nab-paclitaxel weekly for 12 weeks. In the standard arm, patients received 6 weeks of trastuzumab and pertuzumab followed by trastuzumab weekly, pertuzumab every 3 weeks, and paclitaxel weekly for 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or I. Key secondary objectives included pCR rate, safety, and change in tumor size at 6 weeks. Hypothesis-generating correlative assessments were also performed. RESULTS: The 30 evaluable patients were well-balanced in patient and tumor characteristics. The proportion of patients with RCB 0 or I was higher in the experimental arm (100% vs. 62.5% in the standard arm, p = 0.0035). In the ER-positive subset, all patients in the experimental arm achieved RCB 0-I versus 25% in the standard arm (p = 0.0035). Adverse events were similar between the two arms. CONCLUSION: In early-stage HER2-positive breast cancer, the neoadjuvant treatment with T-DM1, lapatinib, and nab-paclitaxel was more effective than the standard treatment, particularly in the ER-positive cohort. TRIAL REGISTRATION: Clinicaltrials.gov NCT02073487 , February 27, 2014.