Injectable PLGA/Fe3O4 implants carrying cisplatin for synergistic magnetic hyperthermal ablation of rabbit VX2 tumor

• Published in: PloS one 2017-05, Vol.12 (5), p.e0177049-e0177049
• Main Authors: Yang, Yang, Wang, Fengjuan, Zheng, Kaiyuan, Deng, Liming, Yang, Lu, Zhang, Nan, Xu, Chunyan, Ran, Haitao, Wang, Zhaoxia, Wang, Zhigang, Zheng, Yuanyi
• Format: Article
• Language: English
• Subjects: Ablation; Accelerated tests; Animal models; Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antitumor activity; Antitumor agents; Apoptosis; Biocompatibility; Biodegradability; Biodegradation; Biology and Life Sciences; Bladder; Blood vessels; Cancer therapies; Carboplatin; Cattle; Cell death; Chemotherapy; Children; Cisplatin; Cisplatin - administration & dosage; Coagulation; Computational fluid dynamics; Control; Cytotoxicity; Degradation; Drug Carriers; Drug delivery systems; Drugs; Effectiveness; Ferromagnetism; Ferrosoferric Oxide - administration & dosage; Fever; Folding; Heat; Hyperthermia; Immune system; Immunotherapy; In Vitro Techniques; In vivo methods and tests; Injection; Iron; Iron oxides; Laboratories; Lactic Acid - administration & dosage; Lasers; Leakage; Liming; Liver - drug effects; Magnetic fields; Magnetic properties; Magnetics; Media; Medicine and Health Sciences; Melanoma; Mice; Mortality; Multidrug resistance; Nanoparticles; Neoplasms, Experimental - drug therapy; Ovarian cancer; Ovarian carcinoma; Peritoneum; Phase shift; Platinum; Polyglycolic Acid - administration & dosage; Precipitates; Rabbits; Regulations; Research and Analysis Methods; Side effects; Skin; Surgery; Surgical implants; Synergism; Temperature effects; Toxicity; Transformation; Transplants & implants; Tumor cells; Tumors; Ultrasonic imaging; Ultrasound; Urinary bladder; Vessels; Viruses; Xenografts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0177049

Magnetic hyperthermia ablation has attracted wide attention in tumor therapy for its minimal invasion. Although the chemo-hyperthermal synergism has been proven to be effective in subcutaneously xenografted tumors of nude mice in our previous experiment, the occurrence of residual tumors due to incomplete ablation is more common in relatively larger and deeper-seated tumors in anti-tumor therapy. Thus, a larger tumor and larger animal model are needed for further study of the therapeutic efficacy. In this study, we tested the efficiency of this newly developed technique using a rabbit tumor model. Furthermore, we chose cisplatin (DDP), which has been confirmed with high efficiency in enhancing hyperthermia therapy as the chemotherapeutic drug for the synergistic magnetic hyperthermal ablation therapy of tumors. In vitro studies demonstrated that developed DDP-loaded magnetic implants (DDP/PLGA-Fe3O4) have great heating efficacy and the drug release can be significantly boosted by an external alternating magnetic field (AMF). In vivo studies showed that the phase-transitional DDP/PLGA-Fe3O4 materials that are ultrasound (US) and computerized tomography (CT) visible can be well confined in the tumor tissues after injection. When exposed to AMF, efficient hyperthermia was induced, which led to the cancer cells' coagulative necrosis and accelerating release of the drug to kill residual tumors. Furthermore, an activated anti-tumor immune system can promote apoptosis of tumor cells. In conclusion, the DDP/PLGA-Fe3O4 implants can be used efficiently for the combined chemotherapy and magnetic-hyperthermia ablation of rabbit tumors.