Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.
Deep tissue imaging in the second near‐infrared (NIR‐II) window holds great promise for widespread fundamental research. However, inhomogeneous signal attenuation due to tissue absorption and scattering hampers its application for accurate in vivo biosensing. Here, lifetime‐based in situ hepatocellular carcinoma (HCC) detection in NIR‐II region is presented using a tumor‐microenvironment (peroxynitrite, ONOO−)‐responsive lanthanide–cyanine Förster resonance energy transfer (FRET) nanosensor. A specially designed ONOO−‐responsive NIR‐II dye, MY‐1057, is synthesized as the FRET acceptor. Robust lifetime sensing is demonstrated to be independent of tissue penetration depth. Tumor lesions are accurately distinguished from normal tissue due to the recovery lifetime. Magnetic resonance imaging and liver dissection results illustrate the reliability of lifetime‐based detection in single and multiple HCC models. Moreover, the ONOO− amount can be calculated according to the standard curve.
Organic dyes emitting in the second near‐infrared (NIR‐II, 900–1700 nm) window, with high molar extinction coefficients (MEC) and quantum yields (QY) in aqueous, are essential for in vivo bioimaging and biosensing. In this work, we developed a dibodipy‐based aggregation‐induced emission (AIE) fluorescent probe, THPP, to meet this aim. THPP exhibits a high MEC and has intensified absorption and emission in J‐aggregated state, which significantly enhance the fluorescence intensity (≈55 folds) and extend the maximal absorption/emission wavelengths to 970/1010 nm in NIR‐II region. Based on the bright THPP, imaging with a high frame rate (34 frames per second) at a deep “valid penetration depth” up to 6 mm can be achieved. This enabled simultaneous and dynamic imaging of vasculatures and deep tissues. Besides, we succeeded in monitoring the respiratory rate of acute‐lung‐injury mice and tracing the collateral circulation process with a high frame rate.
The nose-to-brain pathway has been proven to be a shortcut for direct drug delivery to the brain. However, whether and to what extent nanoparticles can be delivered through this passage is still awaiting validation with evidence. In this study, nose-to-brain transportation of nanoparticles is tracked via fluorescence bioimaging strategies using nanoemulsions (NEs) as model carriers. Identification of NEs in biological tissues is based on the on → off signal switching of a new type of environment-responsive embedded dyes, P2 and P4, and two conventional probes, DiR and coumarin-6 (C6), are embedded to represent the cargoes. Evidence for the translocation of NEs was collected either via live imaging or ex vivo histological examination in rats after nasal administration. Results suggest that NEs with a particle size of about 100 nm, either naked or coated with chitosan, have longer retention duration in nostrils and slower mucociliary clearance than larger ones. P2 signals, representing integral NEs, can be found in mucosa and trigeminal nerves for all size groups, whereas only weak P2 signals are detected in the olfactory bulb for chitosan-coated NEs of 100 nm. Confocal microscopy further confirms the translocation of integral 100 nm NEs in nasal mucosa and along the trigeminal nerve in decremental intensity. Weak signals of the P4 probe, also representing integral NEs, can be detected in the olfactory bulb but few in the brain. NEs as large as 900 nm cannot be transported to the olfactory bulb. However, the DiR or C6 signals that represent the cargoes can be found in significant amounts along the nose-to-brain pathway and finally reach the brain. Evidence shows that integral NEs can be delivered to the olfactory bulb, but few to the brain, whereas the cargoes can be released and permeated into the brain in greater amounts.
Inflammation usually results in high‐level reactive oxygen species (ROS) and reactive nitrogen species (RNS) not only in acidic tissue but also in alkaline tissue. However, noninvasively in vivo monitoring reactive species specifically within alkaline tissue remains a huge challenge. Here we introduce a dual activatable fluorescent probe PN910 located in the second near‐infrared window (NIR‐II, 900–1700 nm), which shows high selectivity toward H2O2 and OONO− at pH beyond 7.4. Then we verified that PN910 could be used for the real‐time, specific and accurate monitoring of cystitis and colitis for living animals. This report presents a unique approach to the development of dual activatable probe for in vivo biosensing.
China has a large area of inland salinealkali land, equivalent to 40% of the total cultivated land in the country. The principal features of these lands are high salt content, high pH, and poor soil structure with low water infiltration and poor drainage. These conditions effectively prevent the exploitation of such land for agriculture.
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