Navneet Joshi1, Farnaz Hajizadeh2, Ehsan Ansari Dezfouli3, Angelina Olegovna Zekiy4, Mohsen Nabi Afjadi5, Seyedeh Mahboubeh Mousavi6, Mohammad Hojjat-Farsangi7, Vahid Karpisheh6, Ata Mahmoodpoor8, Hadi Hassannia9, Sanam Dolati10, Hamed Mohammadi11, Mehdi Yousefi12, Farhad Jadidi-Niaragh13. 1. Department of Biosciences, Mody University of Science and Technology, Lakshmangarh, Rajasthan, India. Electronic address: navybiotech@gmail.com. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Nanobiotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran. 4. Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Moscow, Russia. 5. Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran. 6. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 7. Bioclinicum, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden. 8. Department of Anesthesiology, School of Medicine, Imam Reza Medical Research & Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. 9. Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 10. Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. 11. Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran. 12. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 13. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: jadidif@tbzmed.ac.ir.
Abstract
AIMS: Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death. MATERIALS AND METHODS: We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo. KEY FINDINGS: The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26 cancer models, which was associated with induction of anti-tumor immune responses. SIGNIFICANCE: These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.
AIMS: Despite extensive efforts to find new treatments, chemotherapy is still one of the first and foremost choices for cancer treatment. The main problems of using these drugs are the resistance of cancer cells and reducing their sensitivity to chemotherapy as well as the side effects of their systemic administration. Because STAT3 plays a very important role in the survival and susceptibility of cancer cells to apoptosis, we hypothesized that suppression of STAT3 expression could induce greater susceptibility to DOX-induced cancer cell death. MATERIALS AND METHODS: We used pegylated chitosan lactate nanoparticles (NPs) functionalized by TAT peptide and folate to deliver STAT3 siRNA and DOX to cancer cells simultaneously, both in vitro and in vivo. KEY FINDINGS: The results showed that NPs could effectively deliver siRNA and DOX to cancer cells, which was associated with suppression of STAT3 expression and increased induction of DOX-mediated cell death. Concomitant delivery of DOX and STAT3 siRNA also suppressed tumor growth in 4T1 and CT26cancer models, which was associated with induction of anti-tumor immune responses. SIGNIFICANCE: These findings suggest that the use of NPs can be an effective strategy for the targeted delivery of STAT3-specific siRNA/DOX to cancer cells.