An ultrasensitive polydopamine bi-functionalized SERS immunoassay for exosome-based diagnosis and classification of pancreatic cancer.

Early diagnosis and metastasis monitoring for pancreatic cancer are extremely difficult due to a lack of sensitive liquid biopsy methods and reliable biomarkers. Herein, we developed easy-to-prepare and effective polydopamine-modified immunocapture substrates and an ultrathin polydopamine-encapsulated antibody-reporter-Ag(shell)-Au(core) multilayer (PEARL) Surface-Enhanced Raman Scattering (SERS) nano-tag with a quantitative signal of the Raman reporter at 1072 cm-1, which achieved ultrasensitive and specific detection of pancreatic cancer-derived exosomes with a detection limit of only one exosome in 2 µL of sample solution (approximately 9 × 10-19 mol L-1). Furthermore, by analyzing a 2 µL clinical serum sample, the migration inhibitory factor (MIF) antibody-based SERS immunoassay could not only discriminate pancreatic cancer patients (n = 71) from healthy individuals (n = 32), but also distinguish metastasized tumors from metastasis-free tumors, and Tumor Node Metastasis (TNM) P1-2 stages from the P3 stage (the discriminatory sensitivity was 95.7%). Thus, this novel immunoassay provides a powerful tool for the early diagnosis, classification and metastasis monitoring of pancreatic cancer patients.

An intelligent and biocompatible photosensitizer conjugated silicon quantum dots-MnO2 nanosystem for fluorescence imaging-guided efficient photodynamic therapy.

Photodynamic therapy (PDT) has been widely applied in cancer treatment due to minimal invasion, negligible side effects and specific tumor ablation. However, the treatment efficiency has been hindered by hypoxia in solid tumors, hydrophobic photosensitizers and their real time tracking. In this paper, we constructed an intelligent and biocompatible bovine serum albumin (BSA)-Ce6-Si QDs-MnO2 (BCSM NPs) nanocomplex as a pH/H2O2 responsive photosensitizer nanocarrier to modulate tumor hypoxia for fluorescence imaging-guided efficient PDT. This versatile nanosystem not only enhanced the loading capacity of the photosensitizer and the formation of cytotoxic singlet oxygen (1O2) owing to the intelligent production of oxygen catalyzed by MnO2 from the endogenous H2O2, but also performed as a dual functional fluorescence and Magnetic Resonance imaging (MRI) probe. In vivo experiments in nude mice further confirmed that BCSM NPs significantly inhibited the growth of HeLa bearing-tumors compared to free Ce6. The results highlight the great potentail of multifunctional BCSM NPs for in vivo imaging as well as enhancing the photodynamic therapy efficiency.

Self-Assembled ZnO Nanoparticle Capsules for Carrying and Delivering Isotretinoin to Cancer Cells.

ZnO@polymer core-shell nanoparticles are assembled into novel capsule shells with diameters of about 100 nm to load isotretinoin (ISO) with a capacity as high as 34.6 wt %. Although ISO, a widely used drug for acne treatment, by itself is not suitable for treating cancer because of its hydrophobicity, our ZnO-ISO composite showed much stronger anticancer activity. The improved cytotoxicity is ascribed to the synergistic effects of the ZnO@polymer and ISO, where the ZnO@polymer helps in the accumulation of ISO in cancer cells on the one hand, and on the other hand, ISO is released completely through ZnO decomposition under acidic conditions of cancer cells. Such a pH-triggered drug-delivery system exhibits a much improved killing of cancer cells in vitro in comparison with the benchmarks, Nintedanib and Crizotinib, two commercial drugs clinically applied against lung cancer.

ZnO-Based Nanoplatforms for Labeling and Treatment of Mouse Tumors without Detectable Toxic Side Effects.

ZnO quantum dots (QDs) were synthesized with polymer shells, coordinated with Gd(3+) ions and adsorbed doxorubicin (DOX) together to form a new kind of multifunctional ZnO-Gd-DOX nanoplatform. Such pH sensitive nanoplatforms were shown to release DOX to cancer cells in vitro and to mouse tumors in vivo, and reveal better specificity and lower toxicity than free DOX, and even better therapeutic efficacy than an FDA approved commercial DOX-loading drug DOX-Liposome Injection (DOXIL, NDA#050718). The ZnO-Gd-DOX nanoplatforms exhibited strong red fluorescence, which benefited the fluorescent imaging on live mice. Due to the special structure of ZnO-Gd-DOX nanoparticles, such nanoplatforms possessed a high longitudinal relaxivity r1 of 52.5 mM(-1) s(-1) at 0.55 T, which was superior to many other Gd(3+) based nanoparticles. Thus, both fluorescence labeling and magnetic resonance imaging could be applied simultaneously on the tumor bearing mice along with drug delivery. After 36 days of treatment on these mice, ZnO-Gd-DOX nanoparticles greatly inhibited the tumor growth without causing any appreciable abnormality in major organs. The most important merit of ZnO-Gd-DOX was that such a nanoplatform was biodegraded completely and showed no toxic side effects after H&E (hematoxylin and eosin) staining of tumor slices and ICP-AES (inductively coupled plasma atomic emission spectrometry) bioanalyses.

In situ monitoring of intracellular controlled drug release from mesoporous silica nanoparticles coated with pH-responsive charge-reversal polymer.

Therapeutic platforms such as chemotherapy that respond to physical and biological stimuli are highly desirable for effective cancer therapy. In this study, pH-responsive charge-reversal, polymer-coated mesoporous silica nanoparticles [PAH-cit/APTES-MSNs; PAH-cit refers to poly(allylamine)-citraconic anhydride; APTES refers to (3-aminopropyl)triethoxysilane] were synthesized for application as drug-delivery systems for the treatment of malignant cells. Confocal laser scanning microscopy (CLSM) revealed that the PAH-cit/APTES-MSNs nanocomposite effectively delivered and released doxorubicin hydrochloride to the nucleus of HeLa (human cervical carcinoma) cells. Additionally, the real-time dynamic drug-release process was monitored by CLSM. The current pH-controlled-smart-release platform holds promise in drug-delivery and cancer therapy-related applications.

In situ tracking the intracellular delivery of antisense oligonucleotides by fluorescein doped silica nanoparticles.

Antisense oligonucleotides (ASOs) are often utilized to interfere with gene expression at mRNA level for cancer treatment. Here, we synthesized fluorescein doped silica nanoparticles (FSNPs) and coated them by polyethyleneimine (PEI) for carrying ASOs. Agarose gel electrophoresis proved that PEI/FSNPs could load ASOs by a weight ratio as high as 30:1. We tracked the delivery process of ASOs from the ASOs/PEI/FSNPs composites to HeLa cells in situ by the confocal laser scanning microscopy (CLSM) techniques, including nuclear staining and Z-axis scanning. We found the ASOs/PEI/FSNPs composites exhibited their biological effects at specific intracellular localization, and the fluorescence of the FSNPs showed the dynamic delivery process in the cells.

Nitrogen-doped carbon dots derived from polyvinyl pyrrolidone and their multicolor cell imaging.

Nitrogen-doped carbon dots (N-CDs) with a high quantum yield of 19.6% were prepared by calcining polyvinyl pyrrolidone (PVP, K-30), and then modified with 4,7,10-trioxa-1,13-tridecanediamine. The as-prepared N-CDs exhibited excitation-dependent and pH-sensitive photoluminescence. Transmission electron microscopy and Raman spectra demonstrated the graphitic structure of the N-CDs. Fourier transform infrared spectroscopy and x-ray diffraction studies revealed successful passivation and the presence of hydrophilic groups on the surface. Importantly, such modified quantum dots acted as good multicolor cell imaging probes due to their excellent fluorescent properties, low cytotoxicity and fine dispersity.

One-step synthesis of water-dispersible silicon nanoparticles and their use in fluorescence lifetime imaging of living cells.

We report a novel method for synthesizing water-dispersible silicon nanoparticles (Si NPs) with a simple one-step procedure using mild reagents (3-aminopropyl) trimethoxysilane (APTES) and ascorbate sodium (AS). This is the first report of "green" synthesis of Si NPs on a large scale and at low cost. The method involves a quick reaction in a commonly used round bottom flask at room temperature and pressure without additional treatment and any special equipment. The as-prepared Si NPs have an average diameter of 2 nm and an emission band at 530 nm with a full width at half maximum height (FWHM) of 70 nm and a quantum yield (QY) of 0.21. Moreover, the fluorescence lifetime of these Si NPs is much longer than that of native fluorophores in living cells. Therefore, these Si NPs allow effective imaging of living cells with a fluorescence lifetime imaging microscope (FLIM). Using the time gating model in FLIM, an excellent image was obtained in which the auto-fluorescence interference of cellular fluorophores was suppressed demonstrating that the Si NPs are promising probes for cell imaging particularly using the FLIM technique.

A novel electrochemical sensor for probing doxepin created on a glassy carbon electrode modified with poly(4-amino- benzoic acid)/multi-walled carbon nanotubes composite film.

A novel electrochemical sensor for sensitive detection of doxepin was prepared, which was based on a glassy carbon electrode modified with poly(4-aminobenzoic acid)/multi-walled carbon nanotubes composite film [poly(4-ABA)/MWNTs/GCE]. The sensor was characterized by scanning electron microscopy and electrochemical methods. It was observed that poly(4-ABA)/MWNTs/GCE showed excellent preconcentration function and electrocatalytic activities towards doxepin. Under the selected conditions, the anodic peak current was linear to the logarithm of doxepin concentration in the range from 1.0 × 10(-9) to 1.0 × 10(-6) M, and the detection limit obtained was 1.0 × 10(-10) M. The poly(4-ABA)/MWNTs/GCE was successfully applied in the measurement of doxepin in commercial pharmaceutical formulations, and the analytical accuracy was confirmed by comparison with a conventional ultraviolet spectrophotometry assay.

Growth inhibition and induction of early apoptosis by arenicolsterol A, a novel cytotoxic enolic sulphated sterol from the marine annelid, Arenicola cristata.

Arenicolsterol A (ASA), a novel cytotoxic enolic sulphated sterol, was isolated from the marine annelid, Arenicola cristata (AC). Growth inhibition of this compound on cancer cell lines was determined by MTT assay and suppression of tumour stem cells colony formation. The results showed that ASA was selectively cytotoxic on HeLa cell line (IC(50) = 6.00 +/- 1.16 micromol L(- 1) on HeLa cell line, IC(50) = 10.85 +/- 0.97 micromol L(- 1) on 929 cell line and 14.72 +/- 1.55 micromol L(- 1) on NCI-h6 cell line). In addition, the apoptosis induced by ASA was verified from monitoring the stainability with Annexin V and propidium iodine by a fluorescence-activated cell sorter. The experimental data confirmed that ASA could induce apoptosis in HeLa cells by arresting early stage in apoptosis. Meanwhile, the apoptosis was found to be correlative with the inhibition of the protein tyrosine phosphatases (cdc25A, cdc25B, JSP1, etc). Therefore, ASA might be a novel promising precursor of anticancer medicines.