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This study investigates the acoustic response of phospholipid-coated, hydrophobically modified mesoporous silica nanoparticles (PL-HMSNs) for image-guided drug delivery. PL-HMSNs were first stabilized with a PEGylated lipid, DSPE-PEG2k-methoxy, and the effect of particle concentration on the high-intensity focused ultrasound-induced cavitation threshold was explored. We found that increasing the particle concentration from 0 to 200 μg/mL decreased the acoustic pressure threshold for cavitation from ∼14 to ∼11 MPa, depending on the formulation. Dipalmitoylphosphatidylcholine (DPPC)-, distearoylphosphatidylcholine (DSPC)-, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-, and 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC)-HMSNs gave similar cavitation thresholds. Dilauroylphosphatidylcholine (DLPC)-stabilized particles showed little to no cavitation, which was attributed to DLPC's high critical micelle concentration. DOPC-HMSNs had a higher uptake into HTB-9 human urinary bladder cancer cells than DSPC HMSNs, which is consistent with liposome delivery reports using unsaturated lipids. Finally, the effect of mixed lipid tail lengths was investigated by combining fluid-forming DOPC with gel-forming lipids. Cavitation signal intensities for mixed lipid-stabilized HMSNswere significantly higher than those for pure lipids, which was ascribed to reduced line tension of mixed lipids. Our findings highlight that higher particle concentrations and longer lipid tail lengths can lower the cavitation threshold of PL-HMSNs, and combining saturated lipids with DOPC can amplify the cavitation response. These results provide insights for optimizing lipid-stabilized solid ultrasound contrast agents for drug delivery applications and show how common lipid formulations can be imparted with acoustic activity. [ABSTRACT FROM AUTHOR]

Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting. [Display omitted] • Continuous liquid interface production fabricates 3D drug-loaded devices. • Intraoperative 3D printed devices implanted to inhibit tumor recurrence. • Implantable arrowhead array devices offer directional drug release. • Real time 3D printing allows intraoperative implant fabrication. [ABSTRACT FROM AUTHOR]

Immunotherapy is a rapidly developing area of cancer treatment due to its higher specificity and potential for greater efficacy than traditional therapies. Immune cell modulation through the administration of drugs, proteins, and cells can enhance antitumoral responses through pathways that may be otherwise inhibited in the presence of immunosuppressive tumors. Magnetic systems offer several advantages for improving the performance of immunotherapies, including increased spatiotemporal control over transport, release, and dosing of immunomodulatory drugs within the body, resulting in reduced off-target effects and improved efficacy. Compared to alternative methods for stimulating drug release such as light and pH, magnetic systems enable several distinct methods for programming immune responses. First, we discuss how magnetic hyperthermia can stimulate immune cells and trigger thermoresponsive drug release. Second, we summarize how magnetically targeted delivery of drug carriers can increase the accumulation of drugs in target sites. Third, we review how biomaterials can undergo magnetically driven structural changes to enable remote release of encapsulated drugs. Fourth, we describe the use of magnetic particles for targeted interactions with cellular receptors for promoting antitumor activity. Finally, we discuss translational considerations of these systems, such as toxicity, clinical compatibility, and future opportunities for improving cancer treatment. Magnetic materials enable a variety of distinct and promising pathways to treat cancer by immunotherapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Chemoradiotherapy with cisplatin and etoposide is a curative management regimen for both small and non-small cell lung cancers. While the treatment regimen is effective, it also has a high toxicity profile. One potential strategy to improve the therapeutic ratio of chemoradiation is to utilize nanotherapeutics. Nanoparticle formulation of cisplatin and etoposide, however, is challenging due to the significant mismatch in chemical properties of cisplatin and etoposide. Herein we report the formulation of a polymeric nanoparticle formulation of cisplatin and etoposide using a prodrug approach. We synthesized a hydrophobic platinum prodrug, which was then co-delivered with etoposide using a nanoparticle. Using mouse models of lung cancer, we demonstrated that dual-drug loaded nanoparticles are significantly more effective than small molecule chemotherapy in chemoradiotherapy. These results support further investigation of nanoparticle-based drug formulations of combination chemotherapies and the use of nanotherapeutics in chemoradiotherapy. The treatment of lung cancer often involves a combination of chemotherapy and radiation. While it can be effective, it also has a high toxicity profile. Preferential delivery of chemotherapeutics to the tumor while avoiding normal tissue would improve efficacy and lower toxicity. While this is challenging with conventional drug delivery technologies, nanotechnology offers a unique opportunity. In this study, we have engineered nanoparticles that are loaded with combination chemotherapeutics and showed such nanotherapeutics are more effective and less toxic than free chemotherapeutics in chemoradiotherapy. Our work highlights the importance and potential of nanoformulations of combination chemotherapy in chemoradiotherapy and cancer treatment. This approach can be translated clinically and it can have a significant impact on cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Leukocyte inflammatory responses require integrin cell-adhesion molecule signaling through spleen tyrosine kinase (Syk), a non-receptor kinase that binds directly to integrin β-chain cytoplasmic domains. Here, we developed a high-throughput screen to identify small molecule inhibitors of the Syk-integrin cytoplasmic domain interactions. Screening small molecule compound libraries identified the β-lactam antibiotics cefsulodin and ceftazidime, which inhibited integrin β-subunit cytoplasmic domain binding to the tandem SH2 domains of Syk (IC50 range, 1.02–4.9 µM). Modeling suggested antagonist binding to Syk outside the pITAM binding site. Ceftazidime inhibited integrin signaling via Syk, including inhibition of adhesion-dependent upregulation of interleukin-1β and monocyte chemoattractant protein-1, but did not inhibit ITAM-dependent phosphorylation of Syk mediated by FcγRI signaling. Our results demonstrate a novel means to target Syk independent of its kinase and pITAM binding sites such that integrin signaling via this kinase is abrogated but ITAM-dependent signaling remains intact. As integrin signaling through Syk is essential for leukocyte activation, this may represent a novel approach to target inflammation. [ABSTRACT FROM AUTHOR]

The article discusses a study on cellular backpacks for macrophage immunotherapy. It report an engineered particle referred to as a backpack that can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. It also mentions that conserved phenotypes led to reduced metastatic burdens and slowed tumor growths compared with those of mice treated with an equal dose of macrophages with free cytokine.

In this letter, we discuss how to prepare millions of uniform p-type silicon (Si) microparticles using top-down fabrication processes and how to remotely control their dynamics when they are suspended in water and powered by external alternating current (AC) electric fields. These microparticles present positively charged carrier types (majority carriers from boron atom doping in the intrinsic Si) and negatively charged carrier types (minority carriers from the free electrons in the Si lattice), which electrostatically affects their negatively charged surfaces and enables a variety of programmable behaviors, such as directional assembly and propulsion. At high AC electric field frequencies (f > 10 kHz), the microparticles assemble by attractive dielectrophoretic polarization forces. At low electric field frequencies (f ≤ 10 kHz), the microparticles propel by induced-charge electrophoretic flows. The ability to manipulate the electrostatic potential distribution within and around the microparticles (i.e., by controlling electronic carrier types through doping) is useful for designing a number of new dynamic systems and devices with precise control over their behaviors. [ABSTRACT FROM AUTHOR]

Abstract: Acoustic waves are increasingly used to concentrate, separate, and pattern nanoparticles in liquids, but the extent to which nanoparticles of different size and composition can be focused is not well‐defined. This article describes a simple analytical model for predicting the distribution of nanoparticles around the node of a 1D bulk acoustic standing wave over time as a function of pressure amplitude, acoustic contrast factor (i.e., nanoparticle and fluid composition), and size of the nanoparticles. Predictions from this model are systematically compared to results from experiments on gold nanoparticles of different sizes to determine the model's accuracy in estimating both the rate and the degree of nanoparticle focusing across a range of pressure amplitudes. The model is further used to predict the minimum particle size that can be focused for different nanoparticle and fluid compositions, and those predictions are tested with gold, silica, and polystyrene nanoparticles in water. A procedure combining UV‐light and photoacid is used to induce the aggregation of nanoparticles to illustrate the effect of nanoparticle aggregation on the observed degree of acoustic focusing. Overall, these findings clarify the extent to which acoustic resonating devices can be used to manipulate, pattern, and enrich nanoparticles suspended in liquids. [ABSTRACT FROM AUTHOR]

In the last two decades, advances in micro- and nanofabrication have enabled the development of a wide variety of active or "self-propelling" microparticles, which convert energy from their environment into directed motion. While these autonomous entities have shown promise for efficient locomotion on the microscale, their practical utility remains unrealized due to their inability to perform multiple useful tasks on demand. From an engineering perspective, the active particle behavior can be encoded on an individual level by tailoring key design elements such as shape, polarizability, surface pattern, and bulk functionality. This feature article focusses on active particles powered by electric and magnetic fields, as these sources of energy allow the particles to: (1) move in several phenomenologically unique ways, (2) respond in a reliable manner to the field parameters, and (3) interact synergistically to enable multiple functions. It is hypothesized how future generations of such particles may remotely harvest and transduce energy to perform several useful tasks such as biosensing and delivering drugs. As a step toward realizing such particles, several new types of active particles are demonstrated. Finally, a perspective on the future directions of this emerging field is provided by discussing current challenges, potential applications as well as future opportunities. [ABSTRACT FROM AUTHOR]

Locally energized particles form the basis for emerging classes of active matter. The design of active particles has led to their controlled locomotion and assembly. The next generation of particles should demonstrate robust control over their active assembly, disassembly, and reconfiguration. Here we introduce a class of semiconductor microparticles that can be comprehensively designed (in size, shape, electric polarizability, and patterned coatings) using standard microfabrication tools. These custom silicon particles draw energy from external electric fields to actively propel, while interacting hydrodynamically, and sequentially assemble and disassemble on demand. We show that a number of electrokinetic effects, such as dielectrophoresis, induced charge electrophoresis, and diode propulsion, can selectively power the microparticle motions and interactions. The ability to achieve on-demand locomotion, tractable fluid flows, synchronized motility, and reversible assembly using engineered silicon microparticles may enable advanced applications that include remotely powered microsensors, artificial muscles, reconfigurable neural networks and computational systems. [ABSTRACT FROM AUTHOR]