Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy

The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal method.The obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer cells.Cell experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.

Hierarchically self-assembled fluorescent nanoparticles for near-infrared lysosome-targeted imaging

Manipulating emitting properties of fluorescent dyes plays a critical role in various fields such as light emitting materials, living cell imaging, and phototheranostics [1]. In particular, supramolecular strategies, such as complexation-induced quenching, aggregation-induced emission, have attracted ever-growing attention[2]. Near-infrared (NIR) probes have been demonstrated to possess

Dual microenvironmental parameter-responsive lysosome-targeting carbon dots for the high contrast discrimination of a broad spectrum of cancer cells

The development of new carbon dots(CDs)for fluorescence-based cancer diagnosis has recently attracted extensive attention.Diagnosis methods based on ligand-receptor fluorescence suffer from the heterogeneity of receptor expression.Changes in the microenvironments of cancer cells provide opportunities for accurate and broad-spectrum cancer diagnosis.The lysosomes in cancer cells have lower polarity and higher viscosity than normal cells.Based on these two key microenvironmental parameters,dual-responsive CDs with inherent lysosome-targeting ability were synthesized via one-step hydrothermal treatment.The CDs exhibit many advantageous properties including facile synthesis,good water solubility,pH-independent emission,excellent photostability,good biocompatibility,and wash-free imaging ability.The CDs were successfully employed in the fluorescence-based discrimination of a broad spectrum of cancer cells from normal cells with high contrast.The CDs are promising candidates for use in the field of cancer diagnosis.

Rationally designed meso-benzimidazole-pyronin with emission wavelength beyond 700 nm enabling in vivo visualization of acute-liver-injury-induced peroxynitrite

Fluorescent dyes with fluorescence emission above 700 nm are favorable for bio-imaging due to the higher tissue transparency and lower background fluorescence. In this study, we present a mesobenzimidazole-pyronin platform(Si BMs) with fluorescence emission maxima above 700 nm, which possess good cell permeability, photostability, and lysosomal localization. The great photophysical properties of the Si BMs encouraged us to further exploit their application toward bio-imaging. We synthesized the reduced ‘dihydro’ derivative HSi BM3 for sensing ONOO^(-), with high selectivity and sensitivity and a fast fluorescence “off-on” response(within 2 s). Then, we confirmed the potential of HSi BM3 for visualizing exogenous and endogenous ONOO-in cells and mice. More importantly, HSi BM3 was successfully employed for visualizing acute-liver-injury-induced peroxynitrite.

Ratiometric fluorescent detection of acidic pH in lysosome with carbon nanodots

It is significant for cell physiology to keep the homeostasis of p H, and it is highly demanded to develop ratiometric fluorescent sensors toward p H. In this work, under mild condition, through the electrostatic interaction between carbon nanodots（CDs） and organic molecules, two novel ratiometric fluorescence hybrid nanosensors were fabricated for sensing acidic p H. These nanohybrid systems possess dual emission peaks at 455 and 527 nm under a single excitation wavelength of 380 nm in acidic p H condition.With the increasing of p H, the fluorescence of the 1,8-naphthalimide derivative completely quenches,while the blue fluorescence of CDs keeps constant. Furthermore, the CDsàorganic molecular nanohybrids exhibit excellent anti-disturbance ability, reversible p H sensing ability, and a linear response range in wide p H range respectively. Besides the ability to target lysosome, with one of the nanosensor, stimulated p H change has been successfully tracked in a ratiometric manner via fluorescence imaging.

A bright two-photon fluorescent probe for real-time monitoring autophagy in living cells

A novel donor-acceptor(D-A) type of two-photon(TP) fluorescent probe,i.e.Lyso-OSC,based on the lysosome-targeting morpholine group was developed.The polarity sensing coumarin group was functionalized as the acceptor and the 1-vinyl-4-methoxybenzene group was engineered as the donor.The fluorescence intensity and emission maximum wavelength of Lyso-OSC are highly sensitive to the polarity changes of solvent.The two-photon absorption cross-section and tissue penetration depth are up to 254 GM and 150 μm,respectively.The strong fluorescence,high sensitivity to polarity,low cytotoxicity,and accurate lysosome-targeting ability entail Lyso-OSC the excellent performance in detecting the polarity changes ofcellular environment.To this end,a bright,real-time imaging autophagy of living cells has been achieved.

Tuning the Stability of the Polyplex Nanovesicles of Oligonucleotides via a Zinc(Ⅱ)-Coordinative Strategy

Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.