Recent Advances in Nanoplatforms for the Treatment of Osteosarcoma

Exosomes are small, single-membrane, secreted organelles of ∼30 to ∼200 nm in diameter that have the same topology as the cell and are enriched in selected proteins, lipids, nucleic acids, and glycoconjugates. Exosomes contain an array of membrane-associated, high-order oligomeric protein complexes, display pronounced molecular heterogeneity, and are created by budding at both plasma and endosome membranes. Exosome biogenesis is a mechanism of protein quality control, and once released, exosomes have activities as diverse as remodeling the extracellular matrix and transmitting signals and molecules to other cells. This pathway of intercellular vesicle traffic plays important roles in many aspects of human health and disease, including development, immunity, tissue homeostasis, cancer, and neurodegenerative diseases. In addition, viruses co-opt exosome biogenesis pathways both for assembling infectious particles and for establishing host permissiveness. On the basis of these and other properties, exosomes are being developed as therapeutic agents in multiple disease models.

The successful treatment of patients with osteosarcoma requires close cooperation within an experienced multidisciplinary team including pediatric or medical oncologists, surgeons, pathologists and radiologists. Therefore, therapy should be performed in specialized centers able to provide access to the full spectrum of care. As in other rare malignancies, treatment should be administered within prospective multicenter trials. Therapy must include complete surgical removal of all detectable tumor sites as well as multiagent chemotherapy. The chemotherapy regimen should include several or all of the following four drugs: doxorubicin, high-dose methotrexate with leukovorin-rescue, cisplatin and ifosfamide. Preoperative (neoadjuvant) plus postoperative (adjuvant) polychemotherapy should be preferred, because it allows preparation for safe surgery and preparation of the appropriate prosthesis for the individual patient. The choice of the postponed definitive surgical procedure should be influenced by the anatomical site of the primary tumor, its relationship to neighboring structures, such as vessels and nerves, age and growth potential of the patient, and probably also by the response of the tumor to preoperative chemotherapy. A major, as yet unsolved, problem is the dismal prognosis for patients with unresectable or relapsed osteosarcomas. Novel approaches are needed in order to improve their prognosis.

Liposomes - microscopic phospholipid bubbles with a bilayered membrane structure - have received a lot of attention during the past 30 years as pharmaceutical carriers of great potential. More recently, many new developments have been seen in the area of liposomal drugs - from clinically approved products to new experimental applications, with gene delivery and cancer therapy still being the principal areas of interest. For further successful development of this field, promising trends must be identified and exploited, albeit with a clear understanding of the limitations of these approaches.