Downstream studies of circulating tumor cells (CTCs), which may provide indicative evaluation information for therapeutic efficacy, cancer metastases, and cancer prognosis, are seriously hindered by the poor purity of enriched CTCs as large amounts of interfering leukocytes still nonspecifically bind to the isolation platform. In this work, biomimetic immunomagnetic nanoparticles (BIMNs) with the following features are designed: i) the leukocyte membrane camouflage, which could greatly reduce homologous leukocyte interaction and actualize high‐purity CTCs isolation, is easily extracted by graphene nanosheets; ii) facile antibody conjugation can be achieved through the “insertion” of biotinylated lipid molecules into leukocyte‐membrane‐coated nanoparticles and streptavidin conjunction; iii) layer‐by‐layer assembly techniques could integrate high‐magnetization Fe3O4 nanoparticles and graphene nanosheets efficiently. Consequently, the resulting BIMNs achieve a capture efficiency above 85.0% and CTCs purity higher than 94.4% from 1 mL blood with 20–200 CTCs after 2 min incubation. Besides, 98.0% of the isolated CTCs remain viable and can be directly cultured in vitro. Moreover, application of the BIMNs to cancer patients' peripheral blood shows good reproducibility (mean relative standard deviation 8.7 ± 5.6%). All results above suggest that the novel biomimetic nanoplatform may serve as a promising tool for CTCs enrichment and detection from clinical samples.
In vitro liquid biopsy based on exosomes offers promising opportunities for fast and reliable detection of lung cancers. In this work, we present a fluorescence resonance energy transfer (FRET) magnetic...
Telechelic associative polymers (TAPs)
can form a dynamic transient
network in water and have been widely used as rheological modifiers
for improving solution rheological properties in many industrial fields.
In this work, we designed and prepared a novel photoresponsive coumarin-functionalized
telechelic associative model polymer (CouTAP), which was used to investigate
the influence of light-induced dimerization of coumarin end groups
on the polymer structure and solution rheological properties. The
effects of light intensity, irradiation time, polymer concentration,
and temperature on the transient network and rheological behavior
of the CouTAP aqueous solution were studied in detail. The rheological
properties of the dimerized CouTAP aqueous solution show weak temperature
dependence, and the dynamics hardly depends on concentration due to
the transformation of triblock to multiblock polymers. A novel transient
network model composed of train loops and bridges covalently linked
to train loops was proposed to describe the unique solution properties.
This work will not only provide new insights into the influence of
the light-induced dimerization of coumarin end groups on the network
structure and rheological properties of CouTAP solution but also opens
a new perspective for the controlled self-assembly of amphiphilic
polymers and some special applications of TAPs in the manufacturing
and transmission of soft materials, waterborne coating, inks, medicines,
cosmetics, and so on.
In this work, we presented ternary nanoparticles [poly(carboxybetaine methacrylate) (pCBMA)(peptide dendrimer-modified carbon dots (CD-D)/doxorubicin (DOX))] based on peptide dendritic carbon dots (CDs) to realize tumor-specific drug delivery and highly efficient cancer therapy. The versatile nanoparticles could achieve "stealth" delivery in blood due to the antifouling zwitterion coating. Meanwhile, charge changes of the zwitterions could be moderated during their transportation toward/inside tumor cells, where subtle environmental pH variations acted as potent stimuli to actualize desired functions. In particular, the detachment of the zwitterionic "coat" at the tumor site resulted in the exposure of abundant peripheral guanidine groups on peptide dendritic carbon dots (CD-D/DOX) owing to the extracellular pH environment (pH 6.8)-induced charge conversion. Consequently, the positively charged CD-D/DOX (+7.02 mV) interacted with the negatively charged cancer cell membrane to enhance cellular uptake. After endocytosis, tumor intracellular microenvironments (acidic conditions and high glutathione (GSH) levels) could lead to effective disintegration of the CD-D/DOX entities due to acid-induced protonation of guanidine groups and glutathione-induced cleavage of peptide dendritic components on CDs, and then effective endosomal escape and fast doxorubicin hydrochloride (DOX•HCl) release (73.2% accumulative release within 4 h) were achieved successively. This strategy enabled a 9.19-fold drug release rate at tumor sites in comparison with the one in the physiological environment. Moreover, the excellent fluorescence properties of CDs endowed the pCBMA(CD-D/ DOX) with fluorescence bioimaging function. In view of the above-mentioned advantages, pCBMA(CD-D/DOX) exhibited outstanding antitumor activities both in vitro and in vivo, demonstrating much higher antitumor efficacy and less side effects than the free DOX•HCl.
The rapid development of exosome research provides new insights into the physiological role of exosomes and their significant correlation with human health. Although the exosomes derived from tumor sources...
Subtle tumor micro-environmental pH gradient activates functionalization of the zwitterionic micelles for stealth delivery and intelligent release of anti-cancer drug doxorubicin.
Capture of circulating tumor cells (CTCs) with high efficiency and high purity holds great value for potential clinical applications. Besides the existing problems of contamination from blood cells and plasma proteins, unknown/down‐regulated expression of targeting markers (e.g., antigen, receptor, etc.) of CTCs have questioned the reliability and general applicability of current CTCs capture methodologies based on immune/aptamer‐affinity. Herein, a cell‐engineered strategy is designed to break down such barriers by employing the cell metabolism as the leading force to solve key problems. Generally, through an extracellular vesicle generation way, the cell‐released magnetic vesicles inherited parent cellular membrane characteristics are produced, and then functionalized with dibenzoazacyclooctyne to target and isolate the metabolic labeled rare CTCs. This strategy offers good reliability and broader possibilities to capture different types of tumor cells, as proven by the capture efficiency above 84% and 82% for A549 and HepG2 cell lines as well as an extremely low detection limitation of 5 cells. Moreover, it enabled high purity enrichment of CTCs from 1 mL blood samples of tumor‐bearing mice, only ≈5–757 white blood cells are non‐specific caught, ignoring the potential phenotypic fluctuation associated with the cancer progression.
A multifunctional luminescent immuno-magnetic nanoplatform has achieved fast, efficient, cell-friendly capture and recovery of circulating tumor cells.
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