NDLI: Influence of Hyperthermia on Efficacy and Uptake of Carbon Nanohorn-Cisplatin Conjugates

Content Provider	The American Society of Mechanical Engineers (ASME) Digital Collection
Author	DeWitt, Matthew R. Pekkanen, Allison M. Robertson, John Rylander, Christopher G. Rylander, Marissa Nichole
Copyright Year	2014
Abstract	Single-walled carbon nanohorns (SWNHs) have significant potential for use in photothermal therapies due to their capability to absorb near infrared light and deposit heat. Additionally, their extensive relative surface area and volume makes them ideal drug delivery vehicles. Novel multimodal treatments are envisioned in which laser excitation can be utilized in combination with chemotherapeutic-SWNH conjugates to thermally enhance the therapeutic efficacy of the transported drug. Although mild hyperthermia (41–43 °C) has been shown to increase cellular uptake of drugs such as cisplatin (CDDP) leading to thermal enhancement, studies on the effects of hyperthermia on cisplatin loaded nanoparticles are currently limited. After using a carbodiimide chemical reaction to attach CDDP to the exterior surface of SWNHs and nitric acid to incorporate CDDP in the interior volume, we determined the effects of mild hyperthermia on the efficacy of the CDDP-SWNH conjugates. Rat bladder transitional carcinoma cells were exposed to free CDDP or one of two CDDP-SWNH conjugates in vitro at 37 °C and 42 °C with the half maximal inhibitory concentration (IC50) for each treatment. The in vitro results demonstrate that unlike free CDDP, CDDP-SWNH conjugates do not exhibit thermal enhancement at 42 °C. An increase in viability of 16% and 7% was measured when cells were exposed at 42 deg compared to 37 deg for the surface attached and volume loaded CDDP-SWNH conjugates, respectively. Flow cytometry and confocal microscopy showed a decreased uptake of CDDP-SWNH conjugates at 42 °C compared to 37 °C, revealing the importance of nanoparticle uptake on the CDDP-SWNH conjugate's efficacy, particularly when hyperthermia is used as an adjuvant, and demonstrates the effect of particle size on uptake during mild hyperthermia. The uptake and drug release studies elucidated the difference in viability seen in the drug efficacy studies at different temperatures. We speculate that the disparity in thermal enhancement efficacy observed for free drug compared to the drug SWNH conjugates is due to their intrinsic size differences and, therefore, their mode of cellular uptake: diffusion or endocytosis. These experiments indicate the importance of tuning properties of nanoparticle-drug conjugates to maximize cellular uptake to ensure thermal enhancement in nanoparticle mediated photothermal-chemotherapy treatments.
Starting Page	021003
Ending Page	021010
Page Count	8
File Format	PDF
ISSN	01480731
e-ISSN	15288951
Journal	Journal of Biomechanical Engineering
Volume Number	136
Issue Number	2
DOI	10.1115/1.4026318
Language	English
Publisher	The American Society of Mechanical Engineers
Publisher Date	2014-02-05
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Carbon Diffusion (Physics) Drug delivery systems Drugs Flow (Dynamics) Heat Heating Lasers Microscopy Nanoparticles Particulate matter Patient treatment Temperature Tumors Vehicles
Content Type	Text
Resource Type	Article
Subject	Physiology (medical) Biomedical Engineering

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