Mechanical characterization of erythrocyte-derived optical microparticles by quantitative phase imaging and optical tweezers
04 Mar 2019-Vol. 10887, pp 1088717
TL;DR: Differences in membrane stiffness suggest that the circulation dynamics of μNETs may be altered as compared to native erythrocytes, and may play an important role in the circulation kinetics and biodistribution of these particles.
Abstract: We have fabricated constructs from erythrocytes that contain the near-infrared (NIR) dye, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte mimicking transducers (NETs). Mechanical properties of NETs can play an important role in the circulation kinetics and biodistribution of these particles. We characterize the mechanical properties of erythrocytes, hemoglobin-depleted erythrocytes ghosts (EGs), and micron-sized NETs (μNETs) through analysis of membrane fluctuations measured by quantitative phase imaging, and forces associated with membrane tethers pulled by optical tweezers. EGs were prepared from erythrocytes by hypotonic treatment. μNETs were prepared through hypotonic loading of 25 μM ICG into EGs. Quantitative phase images were obtained by a common-path interferometric phaseshifting system. Approximating the membrane as a sheet of springs, we estimated the stiffness of the membrane of erythrocytes, EGs, and µNETs as 3.0 ± 0.6 pN/μm, 6.5 ± 2.1 pN/μm, and 8.0 ± 2.1 pN/μm. Optical tweezers experiments yielded a similar trend. Differences in membrane stiffness suggest that the circulation dynamics of μNETs may be altered as compared to native erythrocytes.
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TL;DR: A hybrid system to encapsulate CPT inside the amphiphilic micelle and coat it with RBC membrane is developed, which resulted in the increased overall survival of mice treated with the nano formulation and showed strong retention inside the Ehrlich Ascites Carcinoma mice models for at least 72 h, suggesting camouflaging ability conferred by RBC membranes.
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TL;DR: This work investigated the circulation dynamics of micro and nano-sized erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice.
Abstract: Erythrocyte-based carriers can serve as theranostic platforms for delivery of imaging and therapeutic payloads. Engineering these carriers at micro- or nanoscales makes them potentially useful for broad clinical applications ranging from vascular diseases to tumor theranostics. Longevity of these carriers in circulation is important in delivering a sufficient amount of their payloads to the target. We have investigated the circulation dynamics of micro (∼4.95 μm diameter) and nano (∼91 nm diameter) erythrocyte-derived carriers in real time using near-infrared fluorescence imaging, and evaluated the effectiveness of such carrier systems in mediating photothermolysis of cutaneous vasculature in mice. Fluorescence emission half-lives of micro- and nanosized carriers in response to a single intravenous injection were ∼49 and ∼15 min, respectively. A single injection of microsized carriers resulted in a 3-fold increase in signal-to-noise ratio that remained nearly persistent over 1 h of imaging time. Our results also suggest that a second injection of the carriers 7 days later can induce a transient inflammatory response, as manifested by the apparent leakage of the carriers into the perivascular tissue. The administration of the carriers into the mice vasculature reduced the threshold laser fluence to induce photothermolysis of blood vessels from >65 to 20 J/cm2. We discuss the importance of membrane physicochemical and mechanical characteristics in engineering erythrocyte-derived carriers and considerations for their clinical translation.
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"Mechanical characterization of eryt..." refers background in this paper
...The long circulation time of erythrocyte has made them an attractive platform for the delivery of various payloads including optical agents.(1,2) Our group was the first to report the engineering of erythrocyte-derived nano-vesicles doped with the FDA-approved near infrared (NIR) dye, indocyanine green (ICG)....
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