Near-infrared (NIR)-light-modulated photothermal thrombolysis has been investigated to overcome the hemorrhage danger posed by clinical clot-busting substances. A long-standing issue in thrombosis fibrinolytics is the lack of lesion-specific therapy, which should not be ignored. Herein, a novel thrombolysis therapy using photothermal disintegration of a fibrin clot was explored through dual-targeting glycol chitosan/heparindecorated polypyrrole nanoparticles (GCS-PPY-H NPs) to enhance thrombus delivery and thrombolytic therapeutic efficacy. GCS-PPY-H NPs can target acidic/P-selectin high-expression inflammatory endothelial cells/thrombus sites for initiating lesionsite-specific thrombolysis by hyperthermia using NIR irradiation. A significant fibrin clot-clearance rate was achieved with thrombolysis using dual-targeting/modality photothermal clot disintegration in vivo. The molecular level mechanisms of the developed nanoformulations and interface properties were determined using multiple surface specific analytical techniques, such as particle size distribution, zeta potential, electron microscopy, Fourier-transform infrared spectroscopy (FTIR), wavelength absorbance, photothermal, immunofluorescence, and histology. Owing to the augmented thrombus delivery of GCS-PPY-H NPs and swift treatment time, dual-targeting photothermal clot disintegration as a systematic treatment using GCS-PPY-H NPs can be effectively applied in thrombolysis. This novel approach possesses a promising future for thrombolytic treatment.
Electric
cell-substrate impedance sensing (ECIS) is an innovative
approach for the label-free and real-time detection of cell morphology,
growth, and apoptosis, thereby playing an essential role as both a
viable alternative and valuable complement to conventional biochemical/pharmaceutical
analysis in the field of diagnostics. Constant improvements are naturally
sought to further improve the effective range and reliability of this
technology. In this study, we developed poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)
(PEDOT:PSS) conducting polymer (CP)-based bioelectrodes integrated
into homemade ECIS cell-culture chamber slides for the simultaneous
drug release and real-time biosensing of cancer cell viability under
drug treatment. The CP comprised tailored PEDOT:PSS, poly(ethylene
oxide) (PEO), and (3-glycidyloxypropyl)trimethoxysilane (GOPS) capable
of encapsulating antitumor chemotherapeutic agents such as doxorubicin
(DOX), docetaxel (DTX), and a DOX/DTX combination. This device can
reliably monitor impedance signal changes correlated with cell viability
on chips generated by cell adhesion onto a predetermined CP-based
working electrode while simultaneously exhibiting excellent properties
for both drug encapsulation and on-demand release from another CP-based
counter electrode under electrical stimulation (ES) operation. Cyclic
voltammetry curves and surface profile data of different CP-based
coatings (without or with drugs) were used to analyze the changes
in charge capacity and thickness, respectively, thereby further revealing
the correlation between their drug-releasing performance under ES
operation (determined using ultraviolet–visible (UV–vis)
spectroscopy). Finally, antitumor drug screening tests (DOX, DTX,
and DOX/DTX combination) were performed on MCF-7 and HeLa cells using
our developed CP-based ECIS chip system to monitor the impedance signal
changes and their related cell viability results.
Thrombolytic and antithrombotic therapies are limited by short circulation time and the risk of off‐target hemorrhage. Integrating a thrombus‐homing strategy with photothermal therapy are proposed to address these limitations. Using glycol chitosan, polypyrrole, iron oxide and heparin, biomimicking GCPIH nanoparticles are developed for targeted thrombus delivery and thrombolysis. The nanoassembly achieves precise delivery of polypyrrole, exhibiting biocompatibility, selective accumulation at multiple thrombus sites, and enhanced thrombolysis through photothermal activation. To simulate targeted thrombolysis, a microfluidic model predicting thrombolysis dynamics in realistic pathological scenarios is designed. Human blood assessments validate the precise homing of GCPIH nanoparticles to activated thrombus microenvironments. Efficient near‐infrared phototherapeutic effects are demonstrated at thrombus lesions under physiological flow conditions ex vivo. The combined investigations provide compelling evidence supporting the potential of GCPIH nanoparticles for effective thrombus therapy. The microfluidic model also offers a platform for advanced thrombolytic nanomedicine development.
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