Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer

www.nature.com/scientificreports OPEN received: 14 November 2016 accepted: 25 January 2017 Published: 02 March 2017 Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novel agents for photoacoustic imaging-guided photothermal ablation of cancer Panchanathan Manivasagan1, Nhat Quang Bui2, Subramaniyan Bharathiraja1, Madhappan Santha Moorthy1, Yun-Ok Oh1, Kyeongeun Song2, Hansu Seo2, Min Yoon3 & Junghwan Oh1,2 Cancer nanotechnology is emerging as one of the promising strategies combining photothermal therapy (PTT) and photoacoustic imaging (PAI) for the treatment of breast cancer and it has received considerable attention in the recent years because it is minimally invasive, prevents damage to non-targeted regions, permits fast recovery, and involves breast cancer imaging. The present study demonstrates multifunctional biocompatible chitosan-polypyrrole nanocomposites (CS-PPy NCs) as novel agents for photoacoustic imaging-guided photothermal ablation of cancer because of their biocompatibility, conductivity, stability, and strong near-infrared (NIR) absorbance. The CS-PPy NCs are spherical in shape and range 26–94 nm in size with a mean value of 50.54 ± 2.56 nm. The in vitro results demonstrated good biocompatibility of CS-PPy NCs, which can be used in PTT for cancer cells under 808-nm NIR laser irradiation. Tumor-bearing mice fully recovered after treatment with CS-PPy NCs and NIR 808-nm laser irradiation compared to the corresponding control groups. Our research highlights the promising potential of using CS-PPy NCs for photoacoustic imaging-guided photothermal ablation of cancer in preclinical animals, which should be verified in future clinical trials. Development of new nanomaterials for breast cancer theranostics that combines therapeutic and diagnostic applications has attracted much attention in the recent decades1–4. For efficient breast cancer treatment, development of novel nanomaterials capable of reacting to the local tumor environment is required5–7. Light-activated theranostics has received considerable attention as one of the major research areas in the recent decades, particularly in photothermal therapy (PTT)8. PTT has become popular in modern cancer therapy because it successfully kills cancer cells in a target area through heat induced hyperthermia, minimally invasive, permits fast recovery, and prevents damage to non-targeted regions9–12. Compared to the traditional approaches including surgery, chemotherapy, and radiotherapy, PPT is more efficient in tumor ablation and involves minimal risk of damage to healthy tissues13. In recent years, many researchers have focused on developing light-absorbing nanoparticles as novel photothermal agents with strong absorption and scattering in the NIR region, which is a biological transparency14–17. The ability to produce hyperthermic temperatures (>43 °C) at a specific area with externally tunable controls has a major advantage over inducing full-body hyperthermia for cancer therapy18. Human breast cancer is the second most common cause of cancer-related deaths in women and the incidence of breast cancer has increased worldwide in the last few years19. Chemotherapy plays a major role in the management and treatment of cancer. The major drawbacks of chemotherapy are its whole body effects, high price, and low level of efficiency20. Therefore, there is an urgency to develop efficient methods that minimize the side 1 Marine-Integrated Bionics Research Center, Pukyong National University, Busan 48513, Republic of Korea. Department of Biomedical Engineering and Center for Marine-Integrated Biotechnology (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea. 3Department of statistics, College of Natural of Sciences, Pukyong National University, Busan, 48513, Republic of Korea. Correspondence and requests for materials should be addressed to J.O. (email: ) 2 Scientific Reports | 7:43593 | DOI: 10.1038/srep43593 1 www.nature.com/scientificreports/ effects of chemotherapy by specifically delivering the chemotherapeutic agent to only the tumor cells21. PTT is rapidly emerging as one of the promising methods for cancer therapy. Photoacoustic imaging (PAI) is a recently developed technique of biomedical imaging that combines the advantages of optical and acoustic imaging22–24. PAI has been applied in the various medical fields for obtaining anatomic and functional information, breast cancer imaging, brain structural and functional imaging, and quantitative blood flow estimation25–27. Therefore, it is undoubted that the PAI would conduce to accurate locating of cancerous tissue for more precise guidance for PTT. Recently, several nanoparticles (gold nanoparticles (AuNPs), copper sulfide nanoparticles (CuS NPs), polypyrrole nanoparticles (PPy NPs), carbon nanomaterials, prussian blue nanoparticles (PB NPs), and upconversion nanoparticles (UCNPs)) with strong NIR absorbance have been investigated for photothermal therapy28. Because of morphology-dependent NIR absorbing property, gold nanorods, gold nanocages, and gold nanoshells have been explored as photoablation agents for cancer therapy18. However, these NIR absorbing AuNPs have low photostability since their morphology and NIR absorption peak would diminish after a long period of laser irradiation owing to the “melting effect”29. Among all the NIR absorbing nanoparticles, CS-PPy NCs are of particular importance as photoablation agents for localized tumorous PTT because of the excellent biocompatibility, significant photothermal conversion efficacy, and remarkable photostability higher than AuNPs. Marine biopolymers are attractive biomaterials for clinical applications owing to their excellent biocompatibility, biodegradability, inexpensiveness, abundance, stability, ease of surface modification, and nontoxic nature30–32. Chitosan (CS) is a natural biopolymer obtained by the N-deacetylation of chitin. CS has received considerable attention in the recent years for its applications in the cosmeceutical, nutraceutical, and pharmaceuticals industries33. Polypyrrole (PPy) is an organic conductive polymer and it is widely used in organic electronics because of its excellent conductivity, stability, and strong NIR absorbance34. PPy is highly promising in various biomedical applications35. Combining the characteristics of these materials as chitosan-polypyrrole nanocomposites (CS-PPy NCs) could potentially enhance their biocompatibility, stability, conductivity, and strong NIR absorbance. In the present study, we report the CS-PPy NCs for the photoacoustic imaging guided photothermal ablation of cancer. The CS-PPy NCs were characterized via various methods. The photothermal effect performance of the CS-PPy NCs was proven in vitro and in vivo under 808-nm NIR laser irradiation. Additionally, their efficiency in PAI was proven in vivo by scanning mice intratumorally injected with CS-PPy NCs. Results and Discussion Figure 1 shows the fab (...truncated)