Synergistic Administration of Photothermal Therapy and Chemotherapy to Cancer Cells Using Polypeptide-Based Degradable Plasmonic Matrices

Abstract

Aim: Resistance of cancer cells to hyperthermic temperatures and spatial limitations of nanoparticle-induced hyperthermia necessitates the identification of effective combination treatments that can enhance the efficacy of this treatment. Here we show that novel polypeptide-based degradable plasmonic matrices can be employed for simultaneous administration of hyperthermia and chemotherapeutic drugs as an effective combination treatment that can overcome cancer cell resistance to hyperthermia. Method: Novel gold nanorod elastin-like polypeptide matrices were generated and characterized. The matrices were also loaded with the heat-shock protein (HSP)90 inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), currently in clinical trials for different malignancies, in order to deliver a combination of hyperthermia and chemotherapy. Results: Laser irradiation of cells cultured over the plasmonic matrices (without 17-AAG) resulted in the death of cells directly in the path of the laser, while cells outside the laser path did not show any loss of viability. Such spatial limitations, in concert with expression of prosurvival HSPs, reduce the efficacy of hyperthermia treatment. 17-AAG–gold nanorod–polypeptide matrices demonstrated minimal leaching of the drug to surrounding media. The combination of hyperthermic temperatures and the release of 17-AAG from the matrix, both induced by laser irradiation, resulted in significant (>90%) death of cancer cells, while ‘single treatments’ (i.e., hyperthermia alone and 17-AAG alone) demonstrated minimal loss of cancer cell viability (<10%). Conclusion: Simultaneous administration of hyperthermia and HSP inhibitor release from plasmonic matrices is a powerful approach for the ablation of malignant cells and can be extended to different combinations of nanoparticles and chemotherapeutic drugs for a variety of malignancies.

Keywords::

• 17-AAG
• cancer
• combination treatment
• gold nanorod
• heat-shock inhibitor
• hyperthermia
• photothermal ablation
• plasmonic matrix
• prostate cancer

Financial & competing interests disclosure

This work was supported by the National Science Foundation (CBET 0829128), NIH (5R21 CA 133618-02) and the Defense Threat Reduction Agency (HDTRA 1-10-1-019), as well as start-up funds from the state of Arizona to Kaushal Rege, and a Fulton Undergraduate Research Initiative (FURI) Award at ASU to Alisha Nanda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors thank Zaki Megeed and Martin L Yarmush at the Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School in Boston, MA, for helpful discussions. The authors also thank Su Lin and Neal Woodbury at the Biodesign Institute at ASU for access to the laser facility.

Additional information

Funding

This work was supported by the National Science Foundation (CBET 0829128), NIH (5R21 CA 133618-02) and the Defense Threat Reduction Agency (HDTRA 1-10-1-019), as well as start-up funds from the state of Arizona to Kaushal Rege, and a Fulton Undergraduate Research Initiative (FURI) Award at ASU to Alisha Nanda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.