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1. Opto-thermoelectric microswimmers

   https://doi.org/10.1038/s41377-020-00378-5  

   Peng, Xiaolei; Chen, Zhihan; Kollipara, Pavana_Siddhartha; Liu, Yaoran; Fang, Jie; Lin, Linhan; Zheng, Yuebing (August 2020, Light: Science & Applications)

   Abstract Inspired by the “run-and-tumble” behaviours of Escherichia coli (E. coli) cells, we develop opto-thermoelectric microswimmers. The microswimmers are based on dielectric-Au Janus particles driven by a self-sustained electrical field that arises from the asymmetric optothermal response of the particles. Upon illumination by a defocused laser beam, the Janus particles exhibit an optically generated temperature gradient along the particle surfaces, leading to an opto-thermoelectrical field that propels the particles. We further discover that the swimming direction is determined by the particle orientation. To enable navigation of the swimmers, we propose a new optomechanical approach to drive the in-plane rotation of Janus particles under a temperature-gradient-induced electrical field using a focused laser beam. Timing the rotation laser beam allows us to position the particles at any desired orientation and thus to actively control the swimming direction with high efficiency. By incorporating dark-field optical imaging and a feedback control algorithm, we achieve automated propelling and navigation of the microswimmers. Our opto-thermoelectric microswimmers could find applications in the study of opto-thermoelectrical coupling in dynamic colloidal systems, active matter, biomedical sensing, and targeted drug delivery. 

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2. Developing New Peptides and Peptide–Drug Conjugates for Targeting the FGFR2 Receptor-Expressing Tumor Cells and 3D Spheroids

   https://doi.org/10.3390/biomimetics9090515  

   Biggs, Mary A; Das, Amrita; Goncalves, Beatriz G; Murray, Molly E; Frantzeskos, Sophia A; Hunt, Hannah L; Phan, Chau_Ahn N; Banerjee, Ipsita A (August 2024, Biomimetics)

   In this work, we utilized a biomimetic approach for targeting KATO (III) tumor cells and 3D tumoroids. Specifically, the binding interactions of the bioactive short peptide sequences ACSAG (A-pep) and LPHVLTPEAGAT (L-pep) with the fibroblast growth factor receptor (FGFR2) kinase domain was investigated for the first time. Both peptides have been shown to be derived from natural resources previously. We then created a new fusion trimer peptide ACSAG-LPHVLTPEAGAT-GASCA (Trimer-pep) and investigated its binding interactions with the FGFR2 kinase domain in order to target the fibroblast growth factor receptor 2 (FGFR2), which is many overexpressed in tumor cells. Molecular docking and molecular dynamics simulation studies revealed critical interactions with the activation loop, hinge and glycine-rich loop regions of the FGFR2 kinase domain. To develop these peptides for drug delivery, DOX (Doxorubicin) conjugates of the peptides were created. Furthermore, the binding of the peptides with the kinase domain was further confirmed through surface plasmon resonance studies. Cell studies with gastric cancer cells (KATO III) revealed that the conjugates and the peptides induced higher cytotoxicity in the tumor cells compared to normal cells. Following confirmation of cytotoxicity against tumor cells, the ability of the conjugates and the peptides to penetrate 3D spheroids was investigated by evaluating their permeation in co-cultured spheroids grown with KATO (III) and colon tumor-associated fibroblasts (CAFs). Results demonstrated that Trimer-pep conjugated with DOX showed the highest permeation, while the ACSAG conjugate also demonstrated reasonable permeation of the drug. These results indicate that these peptides may be further explored and potentially utilized to create drug conjugates for targeting tumor cells expressing FGFR2 for developing therapeutics. 

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3. Modulation of acoustofluidic parameters to assess effect on molecular loading in human T cells.

   https://doi.org/10.1121/10.0007543  

   Centner, Connor; Moore, John; Baxter, Mary; Vinseiro Figueira, Mariana; Long, Zachary; Belott, Clinton; Menze, Michael; Bates, Paula; Yaddanapudi, Kavitha; Kopechek, Jonathan. (October 2021, The journal of the Acoustical Society of America)

   T-cell therapies are rapidly emerging for treatment of cancer and other diseases but are limited by inefficient non-viral delivery methods. Acoustofluidic devices are in development to enhance non-viral delivery to cells. The effect of acoustofluidic parameters, such as channel geometry, on molecular loading in human T cells was assessed using 3D-printed acoustofluidic devices. Devices with rectilinear channels (1- and 2-mm diameters) were compared directly with concentric spiral channel geometries. Intracellular delivery of a fluorescent dye (calcein, 100 lg/ml) was evaluated in Jurkat T cells using flow cytometry after ultrasound treatment with cationic microbubbles (2.5% v/v). B-mode ultrasound pulses (2.5 MHz, 3.8 MPa output pressure) were generated by a P4-1 transducer on a Verasonics Vantage ultrasound system. Cell viability was assessed using propidum iodine staining (10 lg/ml). Intracellular molecular delivery was significantly enhanced with acoustofluidic treatment in each channel geometry, but treatment with the 1-mm concentric spiral geometry further enhanced delivery after acoustofluidic treatment compared to both 1- and 2-mm rectilinear channels (ANOVA p < 0.001, n ¼ 6/group). These results indicate that 3Dprinted acoustofluidic devices enhance molecular delivery to T cells, and channel geometry modulates intracellular loading efficiency. This approach may offer advantages to improve manufacturing of T cell therapies. 

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4. Achieving Targeted Delivery of Chemotherapeutic Particles to Small Airway Tumors via Pulmonary Route Using Endotracheal Catheters: A CFPD Study

   https://doi.org/10.3390/ph16020158  

   Islam, Mohammad Rashedul; Feng, Yu (February 2023, Pharmaceuticals)

   Tracheobronchial tumors, while uncommon, are often malignant in adults. Surgical removal is the primary therapy for non-metastatic lung malignancies, but it is only possible in a small percentage of non-small-cell lung cancer patients and is limited by the number and location of tumors, as well as the patient’s overall health. This study proposes an alternative treatment: administering aerosolized chemotherapeutic particles via the pulmonary route using endotracheal catheters to target lung tumors. To improve delivery efficiency to the lesion, it is essential to understand local drug deposition and particle transport dynamics. This study uses an experimentally validated computational fluid particle dynamics (CFPD) model to simulate the transport and deposition of inhaled chemotherapeutic particles in a 3-dimensional tracheobronchial tree with 10 generations (G). Based on the particle release maps, targeted drug delivery strategies are proposed to enhance particle deposition at two lung tumor sites in G10. Results indicate that controlled drug release can improve particle delivery efficiencies at both targeted regions. The use of endotracheal catheters significantly affects particle delivery efficiencies in targeted tumors. The parametric analysis shows that using smaller catheters can deliver more than 74% of particles to targeted tumor sites, depending on the location of the tumor and the catheter diameter used, compared to less than 1% using conventional particle administration methods. Furthermore, the results indicate that particle release time has a significant impact on particle deposition under the same inhalation profile. This study serves as a first step in understanding the impact of catheter diameter on localized endotracheal injection for targeting tumors in small lung airways. 

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5. Ultrasound-Responsive Nanobubbles for Combined siRNA-Cerium Oxide Nanoparticle Delivery to Bone Cells

   https://doi.org/10.3390/pharmaceutics15102393  

   Sotoudeh_Bagha, Pedram; Kolanthai, Elayaraja; Wei, Fei; Neal, Craig J; Kumar, Udit; Braun, Gillian; Coathup, Melanie; Seal, Sudipta; Razavi, Mehdi (October 2023, Pharmaceutics)

   This study aims to present an ultrasound-mediated nanobubble (NB)-based gene delivery system that could potentially be applied in the future to treat bone disorders such as osteoporosis. NBs are sensitive to ultrasound (US) and serve as a controlled-released carrier to deliver a mixture of Cathepsin K (CTSK) siRNA and cerium oxide nanoparticles (CeNPs). This platform aimed to reduce bone resorption via downregulating CTSK expression in osteoclasts and enhance bone formation via the antioxidant and osteogenic properties of CeNPs. CeNPs were synthesized and characterized using transmission electron microscopy and X-ray photoelectron spectroscopy. The mixture of CTSK siRNA and CeNPs was adsorbed to the surface of NBs using a sonication method. The release profiles of CTSK siRNA and CeNPs labeled with a fluorescent tag molecule were measured after low-intensity pulsed ultrasound (LIPUS) stimulation using fluorescent spectroscopy. The maximum release of CTSK siRNA and the CeNPs for 1 mg/mL of NB-(CTSK siRNA + CeNPs) was obtained at 2.5 nM and 1 µg/mL, respectively, 3 days after LIPUS stimulation. Then, Alizarin Red Staining (ARS) was applied to human bone marrow-derived mesenchymal stem cells (hMSC) and tartrate-resistant acid phosphatase (TRAP) staining was applied to human osteoclast precursors (OCP) to evaluate osteogenic promotion and osteoclastogenic inhibition effects. A higher mineralization and a lower number of osteoclasts were quantified for NB-(CTSK siRNA + CeNPs) versus control +RANKL with ARS (p < 0.001) and TRAP-positive staining (p < 0.01). This study provides a method for the delivery of gene silencing siRNA and CeNPs using a US-sensitive NB system that could potentially be used in vivo and in the treatment of bone fractures and disorders such as osteoporosis. 

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