A human-in-the-loop haptic interaction with subjective evaluation

To date, one of the challenges in Human-Computer Interaction (HCI) is fully immersive multisensory remote physical interaction technologies. The applications of haptic perception in HCI can enrich the interaction details and effectively improve the immersion and realism of interaction. In the human-in-the-loop haptic interaction system, the quality of experience (QoE) of the human operator plays an essential role. However, QoE in haptic interaction is still in its infancy. Based on the typical application scenarios of haptic operation, the paper constructs a haptic-visual interaction framework and analyzes the QoE influencing factors. Through subjective evaluation experiments, the paper establishes a haptic interaction database that can provide a research basis for further exploring the relationship between various influencing factors and interactive QoE

Hemoglobin as a Smart pH-Sensitive Nanocarrier To Achieve Aggregation Enhanced Tumor Retention

Natural proteins have been greatly explored to address unmet medical needs. However, few work has treated proteins as natural pH-sensitive nanoplatforms that make use of the inherent pH gradient of pathogenic sites. Here, hemoglobin is employed as a smart pH-sensitive nanocarrier for near-infrared dye IR780, which disperses well at normal tissue pH and exhibits aggregation at tumor acidic milieu. The pH-sensitive hemoglobin loaded with IR780 shows higher uptake by cancer cells at tumor acidic pH 6.5 than normal tissue pH 7.4. In vivo and ex vivo studies reveal that the hemoglobin nanocarrier exhibits distinct retention kinetics with remarkably prolonged residence time in tumor. Hemoglobin is then proved to be a potent pH-sensitive nanocarrier for cancer diagnosis and treatment

Enhanced Retention and Cellular Uptake of Nanoparticles in Tumors by Controlling Their Aggregation Behavior

Effective accumulation of nanoparticles (NPs) in tumors is crucial for NP-assisted cancer diagnosis and treatment. With the hypothesis that aggregation of NPs stimulated by tumor microenvironment can be utilized to enhance retention and cellular uptake of NPs in tumors, we designed a smart NP system to evaluate the effect of aggregation on NPs’ accumulation in tumor tissue. Gold nanoparticles (AuNPs, ∼16 nm) were facilely prepared by surface modification with mixed-charge zwitterionic self-assembled monolayers, which can be stable at the pH of blood and normal tissues but aggregate instantly in response to the acidic extracellular pH of solid tumors. The zwitterionic AuNPs exhibited fast, ultrasensitive, and reversible response to the pH change from pH 7.4 to pH 6.5, which enabled the AuNPs to be well dispersed at pH 7.4 with excellent stealth ability to resist uptake by macrophages, while quickly aggregating at pH 6.5, leading to greatly enhanced uptake by cancer cells. An <i>in vivo</i> study demonstrated that the zwitterionic AuNPs had a considerable blood half-life with much higher tumor accumulation, retention, and cellular internalization than nonsensitive PEGylated AuNPs. A preliminary photothermal tumor ablation evaluation suggested the aggregation of AuNPs can be applied to cancer NIR photothermal therapy. These results suggest that controlled aggregation of NPs sensitive to tumor microenvironment can serve as a universal strategy to enhance the retention and cellular uptake of inorganic NPs in tumors, and modifying NPs with a mixed-charge zwitterionic surface can provide an easy way to obtain stealth properties and pH-sensitivity at the same time

Zwitterionic Phosphorylcholine–TPE Conjugate for pH-Responsive Drug Delivery and AIE Active Imaging

Polymeric micelles have emerged as a promising nanoplatform for cancer theranostics. Herein, we developed doxorubicin (DOX) encapsulated pH-responsive polymeric micelles for combined aggregation induced emission (AIE) imaging and chemotherapy. The novel zwitterionic copolymer poly­(2-methacryl­oyloxyethyl­phosphorylcholine-<i>co</i>-2-(4-formyl­phenoxy)­ethyl methacrylate) (poly­(MPC-<i>co</i>-FPEMA)) was synthesized via RAFT polymerization and further converted to PMPC-<i>hyd</i>-TPE after conjugation of tetraphenylethene (TPE, a typical AIE chromophore) via acid-cleavable hydrazone bonds. The AIE activatable copolymer PMPC-<i>hyd</i>-TPE could self-assemble into spherical PC-<i>hyd</i>-TPE micelles, and DOX could be loaded through hydrophobic interactions. The zwitterionic micelles exhibited excellent physiological stability and low protein adsorption due to the stealthy phosphorylcholine (PC) shell. In addition, the cleavage of hydrophobic TPE molecules under acidic conditions could induce swelling of micelles, which was verified by size changes with time at pH 5.0. The <i>in vitro</i> DOX release profile also exhibited accelerated release rate with pH value decreasing from 7.4 to 5.0. Fluorescent microscopy and flow cytometry studies further demonstrated fast internalization and accumulation of drug loaded PC-<i>hyd</i>-TPE-DOX micelles in HepG2 cells, resulting in considerable time/dose-dependent cytotoxicity. Meanwhile, high-quality AIE imaging of PC-<i>hyd</i>-TPE micelles was confirmed in HepG2 cells. Notably, <i>ex vivo</i> imaging study exhibited efficient accumulation and drug release of PC-<i>hyd</i>-TPE-DOX micelles in the tumor tissue. Consequently, the multifunctional micelles with combined nonfouling surface, AIE active imaging, and pH-responsive drug delivery showed great potential as novel nanoplatforms for a new generation of cancer theranostics

IR-780 Loaded Phospholipid Mimicking Homopolymeric Micelles for Near-IR Imaging and Photothermal Therapy of Pancreatic Cancer

IR-780 iodide, a near-infrared (near-IR) fluorescent dye, can be utilized as an effective theranostic agent for both imaging and photothermal therapy. However, its lipophilicity limits its further biomedical applications. Herein, we synthesized a phospholipid mimicking amphiphilic homopolymer poly­(12-(methacryloyloxy)­dodecyl phosphorylcholine) (PMDPC) via reversible addition–fragmentation chain transfer (RAFT) polymerization. The amphiphilic homopolymer PMDPC can be self-assembled into micelles and used for the encapsulation of IR-780. The IR-780 loaded micelles (PMDPC-IR-780) exhibited low cytotoxicity in the dark, whereas remarkable photothermal cytotoxicity to pancreatic cancer cells (BxPC-3) was observed upon near-IR laser irradiation. We further investigated <i>in vivo</i> biodistribution of PMDPC-IR-780 micelles. Higher accumulation of PMDPC-IR-780 than that of free IR-780 in tumor tissue was verified, which might be ascribed to the enhanced permeability and retention (EPR) effect and long circulation time benefiting from the zwitterionic phosphorylcholine surface. Therefore, the IR-780 loaded phospholipid mimicking homopolymeric micelles could have great potential for cancer theranostics