Nanomedicine: Nanotechnology, Biology and Medicine最新文献

Objective

Perineural invasion (PNI) is associated with local recurrence, distant metastasis, and a poor prognosis in pancreatic cancer. However, rare attempt was made to identified the PNI intraoperative. To facilitate precise R0 excision of the tumor, we planned to develop a fluorescent probe for intraoperative imaging of the PNI using GAP-43 as the target and indocyanine green (ICG) as the carrier.

Methods

The probe was created by binding peptide antibody and ICG. Its targeting was tested in vitro and in vivo using a co-culture model of PC12 and tumor cells to create an in vitro neural invasion model and a mouse sciatic nerve invasion model. The small animal imaging system and surgical navigation system confirmed the probe's potential clinical applicability. The sciatic nerve damage model was created to confirm the probe's targeting.

Results

We used the pancreatic cancer samples and the public database to confirm that GAP-43 was preferentially overexpressed in pancreatic cancer, particularly in PNI. PC12 cells showed high GAP-43RA-PEG-ICG probe-specific absorption after being co-cultured with tumor cells in vitro. In the sciatic nerve invasion experiment, animals in probe group displayed a significantly stronger fluorescence signal at the PNI compared to ICG-NP and the contralateral normal nerves groups. Although only 60 % of mice appeared to have R0 resections by the naked eye, small animal imaging systems and surgical fluorescence navigation systems could remove the tumor with R0 precision. The injury model used in the probe imaging experimental trials demonstrated that the probe was specifically targeted to the injured nerve, regardless of whether the injury was infiltrated by a tumor or physical.

Conclusion

We developed the GAP-43Ra-ICG-PEG, an active-targeting near-infrared fluorescent (NIRF) probe, that specifically binds to GAP-43-positive neural cells in an in vitro model of PNI. The probe efficiently visualized PNI lesions in pancreatic cancer in preclinical models, opening up new possibilities for NIRF-guided pancreatic surgery, particularly for PNI patients.

Acute respiratory distress syndrome (ARDS) has high mortality (~40 %) and requires the lifesaving intervention of mechanical ventilation. A variety of systemic inflammatory insults can progress to ARDS, and the inflamed and injured lung is susceptible to ventilator-induced lung injury (VILI). Strategies to mitigate the inflammatory response while restoring pulmonary function are limited, thus we sought to determine if treatment with CNP-miR146a, a conjugate of novel free radical scavenging cerium oxide nanoparticles (CNP) to the anti-inflammatory microRNA (miR)-146a, would protect murine lungs from acute lung injury (ALI) induced with intratracheal endotoxin and subsequent VILI. Lung injury severity and treatment efficacy were evaluated via lung mechanical function, relative gene expression of inflammatory biomarkers, and lung morphometry (stereology). CNP-miR146a reduced the severity of ALI and slowed the progression of VILI, evidenced by improvements in inflammatory biomarkers, atelectasis, gas volumes in the parenchymal airspaces, and the stiffness of the pulmonary system.

The second near-infrared (NIR-II) fluorescence imaging has attracted continuous attention due to its excellent penetration depth and high spatial resolution. Compared with other fluorophores, NIR-II fluorophores, especially NIR-II organic small molecule fluorophores, are favored because of their controllable structure and good biocompatibility. In this study, we designed and synthesized an S-D-A-D-S type small molecule FEA. However, a new molecule was accidentally obtained in the process of synthesis, which was proved to be a double receptor (A-A) type small molecule, namely S-D-A-A-D-S type organic small molecule FEAA. Compared with FEA molecules, FEAA exhibits superior fluorescence performance and can effectively prevent fluorescence quenching. The fluorescence emission of its nanoparticles (NPs) reaches 1109 nm, extends to about 1400 nm, and has a Stokes shift of up to 472 nm. Subsequently, we realized fluorescence/photoacoustic dual-mode imaging (FI/PAI) of nude mouse liver, and finally effectively ablated 4T1 tumor by photothermal therapy (PTT). In general, FEAA NPs exhibit good fluorescence, photoacoustic, and photothermal effects, and are an excellent multifunctional NIR-II organic small molecule fluorophore. As far as we know, there are few reports on A-A type organic small molecules, most of which are cyanines or D-A-D type structures. Therefore, this study has good exploratory significance and reference value for the discovery of NIR-II fluorophores.

Liver cancer such as hepatocellular carcinoma (HCC) poorly responds to chemotherapeutics as there are no effective means to deliver the drugs to liver cancer. Here we report GalNAc decorated exosomes as cargo for targeted delivery of Paclitaxel (PTX) and miR122 to liver tumors as an effective means to inhibit the HCC. Exosomes (Exos) are nanosized extracellular vesicles that deliver a payload to cancer cells effectively. GalNAc provides Exos targeting ability by binding to the asialoglycoprotein-receptor (ASGP-R) overexpressed on the liver cancer cell surface. A 4-way junction (4WJ) RNA nanoparticle was constructed to harbor 24 copies of hydrophobic PTX and 1 copy of miR122. The 4WJ RNA-PTX complex was loaded into the Exos, and its surface was decorated with GalNAc using RNA nanotechnology to obtain specific targeting. The multi-specific Exos selectively bind and efficiently delivered the payload into the liver cancer cells and exhibited the highest cancer cell inhibition due to the multi-specific effect of miR122, PTX, GalNAc, and Exos. The same was reflected in mice xenograft studies, the liver cancer was efficiently inhibited after systemic injection of the multi-specific Exos. The required effective dose of chemical drugs carried by Exos was significantly reduced, indicating high efficiency and low toxicity. The multi-specific strategy demonstrates that Exos can serve as a natural cargo vehicle for the targeted delivery of anticancer therapeutics to treat difficult-to-treat cancers.

ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in atherosclerotic formation through mediated cholesterol efflux in macrophage-derived foam cells. In this study, a scavenger receptors AI (SR-AI) targeted theranostic nanoparticles was constructed for atherosclerosis regression via ABCA1 activation in foam cells. ABCA1-upregulator 5242331 and IR780 were encapsulated in PLGA-PEG micelles which were conjugated with SR-AI targeting peptide (PP1) to formulate the nanoparticles (SAU-NPs). Immunostaining revealed that SR-AI was highly expressed both in macrophage foam cells and in atherosclerotic plaque of ApoE^−/− mice. The SAU-NPs have shown more active targeting to plaque lesion with higher stability compared with non-SR-AI targeted nanoparticles. The transformation from macrophage to foam cells was inhibited by SAU-NPs carried 5242331. Cholesterol deposition was effectively reduced in foam cells by SAU-NPs through activating the LXRα-ABCA1/ABCG1/SR-BI pathway. In conclusion, theranostic SAU-NPs which carried ABCA1-upregulator 5242331 exert beneficial effects on atherosclerosis regression via LXRα activation.

Urinary tract infections (UTIs) are among the most common bacterial infections. Despite a wide range of therapeutic options, treatment success is compromised by the efficient mechanism of tissue colonization of uropathogenic Escherichia coli. In advanced drug delivery systems, a similar, glycan-mediated targeting mechanism may be realized by conjugating the drug to a plant lectin, like wheat germ agglutinin (WGA).

We introduce a drug delivery vehicle consisting of human serum albumin as nanoparticle shell, olive oil as core component, the active pharmaceutical ingredients (API) trimethoprim and rifampicin as well as WGA to facilitate cellular internalization. When WGA was embedded into the proteinaceous particle shell, cell binding studies revealed up to 60 % higher cell binding potential. Additionally, nanoparticles showed a good efficacy against gram-negative just as against gram-positive bacteria.

The combination of the promising cell-associative properties and the proven antimicrobial potential might lead to an improved efficacy of advanced treatment of UTIs.

Clinical trials incorporating metallic nanoparticles (NPs) have recently begun. Radiotherapy planning does not take into account NPs concentrations observed in the patients' target volumes. In the framework of the NANOCOL clinical trial including patients treated for locally advanced cervical cancers, this study proposes a complete method to evaluate the radiation-induced biological effects of NPs. For this, calibration phantom was developed and MRI sequences with variable flip angles were acquired. This process allowed the quantification of NPs in the tumor of 4 patients, which was compared to the results of mass spectrometry obtained from 3 patient biopsies. The concentration of the NPs was reproduced in 3D cell models. Based on clonogenic assays, the radio-enhancement effects were quantified for radiotherapy and brachytherapy, and the impact in terms of local control was evaluated. T₁ signal change in GTVs revealed NPs accumulation ∼12.4 μmol/L, in agreement with mass spectrometry. Radio-enhancement effects of about 15 % at 2 Gy were found for both modalities, with a positive impact on local tumor control. Even if further follow-up of patients in this and subsequent clinical trials will be necessary to assess the reliability of this proof of concept, this study opens the way to the integration of a dose modulation factor to better take into account the impact of NPs in radiotherapy treatment.

Intravesical instillation has been considered an efficient route for detecting bladder cancer. However, only a small fraction of administered dose permeates into tumor tissues, and insufficient retention time limits their application. In this work, a novel intravesical bidirectional perfusion-like administered mode was developed to improve diagnostic accuracy of bladder tumor imaging. Specifically, the ultrasmall AuPd-P-FA Nanoprobe exhibit excellent NIR-II FL imaging performance due to electronic structure perturbation. Benefiting from the size advantage for kidney metabolism and FA targeting specificity, AuPd-P-FA could effectively administration to bladder tumor. When AuPd-P-FA reached maximum enrichment at 1 h post-injection, the localized and mild thermal energy produced upon laser irradiation activated a phase transition. This thermo-sensitive characteristic could prolong the retention time in bladder and the fluorescence signal could be clearly observed at 6 h post-injection with high accuracy. This novel intravesical bidirectional perfusion-like administered mode is expected to achieve a non-invasive diagnosis of early bladder cancer.

The silica nanoparticles (SNs) co-doped with paramagnetic ([Mn(HL)]^n-,) and luminescent ([Ru(dipy)₃]²⁺) complexes are represented. The specific distribution of [Mn(HL)]^n- within the SNs allows to achieve about ten-fold enhancing in magnetic relaxivities in comparison with those of [Mn(HL)]^n- in solutions. The leaching of [Mn(HL)]^n- from the shell can be minimized through the co-doping of [Ru(dipy)₃]²⁺ into the core of the SNs. The co-doped SNs exhibit colloid stability in aqueous solutions, including those modeling a blood serum. The surface of the co-doped SNs was also decorated by amino- and carboxy-groups. The cytotoxicity, hemoagglutination and hemolytic activities of the co-doped SNs are on the levels convenient for “in vivo” studies, although the amino-decorated SNs cause more noticeable agglutination and suppression of cell viability. The co-doped SNs being intravenously injected into mice allows to reveal their biodistribution in both ex vivo and in vivo conditions through confocal microscopy and magnetic resonance imaging correspondingly.

Oral cancer is a type of cancer that develops in the mouth and is one of the deadliest malignancies in the world. Currently surgical, radiation therapy, and chemotherapy are most common treatments. Better treatment and early detection strategies are required. Chemotherapeutic drugs fail frequently due to toxicity and poor tumor targeting. There are high chances of failure of chemotherapeutic drugs due to toxicity. Active, passive, and immunity-targeting techniques are devised for tumor-specific activity. Nanotechnology-based drug delivery systems are the best available solution and important for precise targeting. Nanoparticles, liposomes, exosomes, and cyclodextrins are nano-based carriers for drug delivery. Nanotechnology is being used to develop new techniques such as intratumoral injections, microbubble mediated ultrasonic therapy, phototherapies, and site-specific delivery. This systematic review delves into the details of such targeted and nano-based drug delivery systems in order to improve patient health and survival rates in oral cancer.