Search

Non-small cell lung cancer (NSCLC) is the leading cause of lung cancer-related deaths worldwide. Tumor-associated macrophages (TAMs), which can be polarized into tumor-promoting M2 phenotype, overexpress folate receptor beta (FRβ) and are associated with poor prognosis in NSCLC. In addition, calpain-2 (CAPN2) is overexpressed in NSCLC and is involved in tumor growth. To improve the anticancer efficacy of drugs and reduce their side effects in the treatment of NSCLC, it is important to develop smart drug delivery systems with specific targeting ability and controlled release mechanisms. In this study, FRβ-targeted pH-sensitive liposomes were designed as carriers to ensure efficient drug delivery and acid-responsive release in NSCLC cells. Folate-mediated targeting of FRβ in M2 TAMs and NSCLC cells effectively inhibited tumor growth and the stimulus-responsive drug release reduced the toxic side effects of the drug. The combination of doxycycline (anti-CAPN2) and docetaxel (anticancer drug) showed a synergistic inhibitory effect on tumor growth by suppressing CAPN2 expression.

The self-organization of colloidal nanoparticles into programmed suprastructures is an important research area in various disciplines of nano, colloid, and polymer sciences. However, despite the re...

Vesicle transport conducted by motor protein multiplexes (MPMs), which is ubiquitous among eukaryotes, shows anomalous and stochastic dynamics qualitatively different from the dynamics of thermal motion and artificial active matter; the relationship between in vivo vesicle-delivery dynamics and the underlying physicochemical processes is not yet quantitatively understood. Addressing this issue, we perform accurate tracking of individual vesicles, containing upconverting nanoparticles, transported by kinesin-dynein-multiplexes along axonal microtubules. The mean-square-displacement of vesicles along the microtubule exhibits unusual dynamic phase transitions that are seemingly inconsistent with the scaling behavior of the mean-first-passage time over the travel length. These paradoxical results and the vesicle displacement distribution are quantitatively explained and predicted by a multimode MPM model, developed in the current work, where ATP-hydrolysis-coupled motion of MPM has both unidirectional and bidirectional modes.

ErbB2 is a type of receptor tyrosine kinase, which is known to be involved in tumorigenesis, tumor aggressiveness, and clinical outcome. ErbB2-targeting therapy using therapeutic antibodies has been successful in breast cancer treatment. However, the need for repeated treatments and the high cost are major disadvantages with monoclonal antibody therapies. Compared with antibodies, peptides are cheap, relatively stable, and have low immunogenicity. We have developed a highly specific cancer-targeting drug delivery system using a targeting peptide to maximize the therapeutic efficiency of rapamycin and to help prevent drug resistance in ErbB2-positive breast cancer. Physicochemical characterization confirmed the successful construction of ErbB2-targeting liposomes (ErbB2Lipo). A comparison of a scrambled peptide (ScrErbB2) with the ErbB2-targeting peptide confirmed that these peptides had similar properties except for the targeting ability. The ErbB2Lipo exhibited higher delivery efficiency in ErbB2 positive BT-474 cells than non-targeting liposomes conjugated with ScrErbB2 (ScrErbB2Lipo). This peptide-targeting strategy has the potential to improve the efficacy of chemotherapy in ErbB2-positive cancers.

Understanding the interaction of nanoparticles with living cells on the basis of cellular uptake efficiency is a fundamental requisite in biomedical research. Cellular internalization of nanoparticles takes place by mechanisms like ATP hydrolysis-driven endocytosis that deliver nanoparticles to the cytoplasm, organelles and nuclei. Despite its importance in nanomedicine, this uptake procedure is not understood in-depth because of the complexity of the biochemical mechanisms and the lack of available experimental methods for quantitative analysis. The only breakthrough is likely to be the development of imaging techniques that can visualize, monitor and even count the number of nanoparticles inside the cell. To this end, we report here a new, fast and background-free three-dimensional (3-D) imaging technique with quantitative evaluation of the uptake efficiency for NaYF4:Yb3+,Er3+/NaYF4 core/shell upconversion nanoparticles (UCNPs) functionalized with different chemical and biological groups. Furthermore, the multiple 3-D trajectories of the UCNPs have been analyzed to investigate the cellular dynamics. This study reveals the nuclear uptake of UCNPs to be dependent on the specific chemical groups conjugated to the UCNPs. The developed 3-D imaging technique is of great significance for exploring complex biological systems.

Because of their well-known optical properties, upconversion nanoparticles (UCNPs) are regarded as some of the most promising nanomaterials for bioimaging, biosensors, and solar cells. The nonblinking nature of their upconversion emissions has been a particularly beneficial advantage for live-cell imaging. However, the origin of this unique property has never been seriously investigated. We report, for the first time, the observation of stochastic photon emission (SPEM) in core/shell UCNPs (NaYF4:Yb3+,Er3+/NaYF4) on the microsecond and nanosecond time scales, even under continuous irradiation at 980 nm. This SPEM was attributed to slow “upconversion cycles”. We consider that the conventionally reported, nonblinking nature of UCNP emissions can be attributed to the averaging of SPEMs from multiple Er3+ ions and the low temporal resolution of previous observation. The off-time distribution, which possesses kinetics information for the upconversion pathways, was well fitted to a single exponential indicating...

The cell membrane-coating strategy has opened new opportunities for the development of biomimetic and multifunctional drug delivery platforms. Recently, a variety of gold nanoparticles, which can combine with blood cell membranes, have been shown to provide an effective approach for cancer therapy. Meanwhile, this class of hybrid nanostructures can deceive the immunological system to exhibit synergistic therapeutic effects. Here, we synthesized red blood cell (RBC) and platelet membrane-coated gold nanostars containing curcumin (R/P-cGNS) and evaluated whether R/P-cGNS had improved anticancer efficacy. We also validated a controlled release profile under near-infrared irradiation for the ability to target melanoma cells and to have an immunomodulatory effect on macrophages. RBC membrane coating provided self-antigens; therefore, it could evade clearance by macrophages, while platelet membrane coating provided targetability to cancer cells. Additionally, the nutraceutical curcumin provided anticancer and anti-inflammatory effects. In conclusion, the results presented in this study demonstrated that R/P-cGNS can deliver drugs to the target region and enhance anticancer effects while avoiding macrophage phagocytosis. We believe that R/P-cGNS can be a new design of the cell-based hybrid system for effective cancer therapy.

Lung cancer is diagnosed at an advanced stage due to its unrecognized symptoms, resulting in high mortality. In recent decades, research into the development of an early diagnostic method for lung cancer has expanded in order to overcome the high mortality rate. Calpain 2 (CAPN2) has been suggested as a tumor marker linked to angiogenesis, cell proliferation, and migration in non-small cell lung cancer. In this study, CAPN2 enzyme-activatable near-infrared peptide sensor linked to human serum albumin (HSA–CAPN2) was developed. Intracellular localization and strong recovered fluorescence signals of HSA–CAPN2 were observed in in vitro experiments using A549-Luc cells, and signal recovery was inhibited by ALLN (a CAPN2 inhibitor). In vivo distribution and signal recovery evaluations performed using A549-Luc cell xenograft mice revealed that HSA–CAPN2 accumulated in the tumor region and produced high fluorescent signal recovery. Three-dimensional reconstructed images using single-plane illumination microscopy...

Upconversion nanoparticles (UCNPs) have attracted enormous interest over the past few years because of their unique optical properties and potential for use in various applications such as bioimaging probes, biosensors, and light-harvesting materials for photovoltaics. The improvement of imaging resolution is one of the most important goals for UCNPs used in biological applications. Super-resolution imaging techniques that overcome the fundamental diffraction limit of light rely on the photochemistry of organic dyes or fluorescent proteins. Here we report our progress toward super-resolution microscopy with UCNPs. We found that the red emission (655 nm) of core/shell UCNPs with the structure NaYF4:Yb3+,Er3+/NaYF4 could be modulated by emission depletion (ED) of the intermediate state that interacts resonantly with an infrared beam (1540 nm). In contrast, the green emission bands (525 and 545 nm) of the UCNPs were less affected by irradiation with the infrared beam. The origin of such distinct behaviors between the green and red emissions was attributed to their different photophysical pathways.

Graphitic carbon nitride (g-C3N4) is widely considered as a promising visible-driven photocatalyst. It is a type of inexpensive, air-stable, and non-toxic material that has been proven to exhibit high performance in photocatalysis. For more efficient use of solar energy, it is necessary to enhance the light absorption of g-C3N4. To take advantage of the near-infrared (NIR) region of the solar energy, g-C3N4 was combined with upconversion nanoparticles (UCNPs), in this study. The UCNPs can convert NIR photons into ultraviolet (UV) and visible light, which can then activate the g-C3N4 photocatalyst. The use of visible and NIR light sources improves the photocatalytic activity of the UCNPs/g-C3N4 nanocomposite. In order to optimize the photocatalytic efficiency of the nanocomposite, the absorption and emission wavelengths of the UCNPs were tuned by controlling the lanthanide dopant composition where the core UCNPs were coated with an inner active shell and an outer inert shell. It is shown in this study that the nanocomposite can exhibit excellent photocatalytic activities under simulated solar light illumination.

Compared to traditional cancer treatments, drug/gene delivery is an advanced, safe, and efficient method. Nanoparticles are widely used as nanocarriers in a drug/gene delivery system due to their long circulation time and low multi-drug resistance. In particular, lanthanide-doped upconversion nanoparticles (UCNPs) that can emit UV and visible light by near-infrared (NIR) upconversion demonstrated more efficient and safer drug/gene delivery. Because of the low penetration depth of UV and visible light, a photoinduced reaction such as photocleavage or photoisomerization has proven restrictive. However, NIR light has high tissue penetration depth and stimulates the photoinduced reaction through UV and visible emissions from lanthanide-doped UCNPs. This review discusses the optical properties of UCNPs that are useful in bioapplications and drug/gene delivery systems using the UCNPs as a photoreaction inducer.