A hyaluronic acid nanogel for photo-chemo theranostics of lung cancer with simultaneous light-responsive controlled release of doxorubicin

• Published in: Nanoscale 2015-06, Vol.7 (24), p.10680-10689
• Main Authors: Khatun, Zehedina, Nurunnabi, Md, Nafiujjaman, Md, Reeck, Gerald R, Khan, Haseeb A, Cho, Kwang Jae, Lee, Yong-kyu
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Apoptosis - drug effects; Apoptosis - radiation effects; Cell Line, Tumor; Chemoradiotherapy - methods; Contrast Media; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemical synthesis; Diffusion; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - radiation effects; Graphite - radiation effects; Graphite - therapeutic use; Humans; Hyaluronic Acid - chemistry; Light; Nanocapsules - administration & dosage; Nanocapsules - chemistry; Nanocapsules - ultrastructure; Nanoconjugates - administration & dosage; Nanoconjugates - chemistry; Neoplasms, Experimental - pathology; Neoplasms, Experimental - therapy; Photochemotherapy - methods; Polyethylene Glycols - chemistry; Polyethyleneimine - chemistry; Theranostic Nanomedicine; Treatment Outcome
• ISSN: 2040-3364; 2040-3372
• DOI: 10.1039/c5nr01075f

The combined delivery of photo- and chemo-therapeutic agents is an emerging strategy to overcome drug resistance in treating cancer, and controlled light-responsive drug release is a proven tactic to produce a continuous therapeutic effect for a prolonged duration. Here, a combination of light-responsive graphene, chemo-agent doxorubicin and pH-sensitive disulfide-bond linked hyaluronic acid form a nanogel (called a graphene-doxorubicin conjugate in a hyaluronic acid nanogel) that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release. The nanogel is mono-dispersed with an average diameter of 120 nm as observed by using TEM and a hydrodynamic size analyzer. It has excellent photo-luminescence properties and good stability in buffer and serum solutions. Graphene itself, being photoluminescent, can be considered an optical imaging contrast agent as well as a heat source when excited by laser irradiation. Thus the nanogel shows simultaneous thermo-chemotherapeutic effects on noninvasive optical imaging. We have also found that irradiation enhances the release of doxorubicin in a controlled manner. This release synergizes therapeutic activity of the nanogel in killing tumor cells. Our findings demonstrate that the graphene-doxorubicin conjugate in the hyaluronic acid nanogel is very effective in killing the human lung cancer cell line (A549) with limited toxicity in the non-cancerous cell line (MDCK).