Effective Cancer Therapy Design Through the Integration of Nanotechnology

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Date
2008-07-25
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Virginia Tech
Abstract

Laser therapies can provide a minimally invasive treatment alternative to surgical resection of tumors. However, therapy effectiveness is limited due to nonspecific heating of target tissue, leading to healthy tissue injury and extended treatment durations. These therapies can be further compromised due to heat shock protein (HSP) induction in tumor regions where non-lethal temperature elevation occurs, thereby imparting enhanced tumor cell viability and resistance to subsequent therapy treatments. Introducing nanoparticles (NPs), such as multi-walled nanotubes (MWNTs) or carbon nanohorns (CNHs), into target tissue prior to laser irradiation increases heating selectivity permitting more precise thermal energy delivery to the tumor region and enhances thermal deposition thereby increasing tumor injury and reducing HSP expression induction. This research investigates the impact of MWNTs and CNHs in untreated and laser-irradiated monolayer cell culture, tissue phantoms, and/or tumor tissue from both thermal and biological standpoints. Cell viability remained high for all unheated NP-containing samples, demonstrating the non-toxic nature of both the nanoparticle and the alginate phantom. Up-regulation of HSP27, 70 and 90 was witnessed in samples that achieved sub-lethal temperature elevations. Tuning of laser parameters permitted dramatic temperature elevations, decreased cell viability, and limited HSP induction in NP-containing samples compared to those lacking NPs. Preliminary work showed MWNT internalization by cells, which presents imaging and multi-modal therapy options for NT use. The lethal combination of NPs and laser light and NP internalization reveals these particles as being viable options for enhancing the thermal deposition and specificity of hyperthermia treatments to eliminate cancer.

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Keywords
multi-walled nanotubes, tissue phantom, laser therapy, carbon nanohorns, hyperthermia, heat shock proteins
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