Iron oxide nanoparticles coated with bioactive materials: a viable theragnostic strategy to improve osteosarcoma treatment

Discover Nano Review Iron oxide nanoparticles coated with bioactive materials: a viable theragnostic strategy to improve osteosarcoma treatment Amy Sarah Benjamin1 · Sunita Nayak2 Received: 21 June 2024 / Accepted: 4 December 2024 © The Author(s) 2025  OPEN Abstract Osteosarcoma (OS) is distinguished as a high-grade malignant tumor, characterized by rapid systemic metastasis, particularly to the lungs, resulting in very low survival rates. Understanding the complexities of tumor development and mutation is the need of the hour for the advancement of targeted therapies in cancer care. A significant innovation in this area is the use of nanotechnology, specifically nanoparticles, to tackle various challenges in cancer treatment. Iron oxide nanoparticles stand out in both therapeutic and diagnostic applications, offering a versatile platform for targeted drug delivery, hyperthermia, magneto-thermal therapy, and combinational therapy using modulation of ferroptosis pathways. These nanoparticles are easy to synthesize, non-toxic, biocompatible, and display enhanced circulation time within the system. They can also be easily conjugated to anti-cancer drugs, targeting agents, or genetic vectors that respond to specific stimuli or pH changes. The surface functionalization of these nanoparticles using bioactive molecules unveils a promising and effective nanoparticle system for assisting osteosarcoma therapy. This review will summarize the current conventional therapies for osteosarcoma and their disadvantages, the synthesis and modification of iron oxide nanoparticles documented in the literature, cellular targeting and uptake mechanism, with focus on their functionalization using natural biomaterials and application strategies towards management of osteosarcoma. The review also compiles the translational challenges and future prospects that must be addressed for clinical advancements of iron oxide based osteosarcoma treatment in the future. Keywords Nanotechnology · Iron oxide nanoparticles · Magnetic properties · Bio-active polymers · Osteosarcoma · Cancer nanomedicine Abbreviations OS Osteosarcoma MNP Magnetic nanoparticles RT Radiation therapy RR Radioresistance SPIONS Super paramagnetic iron oxide nanoparticles TAA Tumour associated antigens PDT Photo dynamic therapy PTT Photo thermal therapy MHT Magnetic hyperthermia FDA Food and drug administration * Sunita Nayak, | 1School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India. 2School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014, India. Discover Nano (2025) 20:18 | https://doi.org/10.1186/s11671-024-04163-w Vol.:(0123456789) Review Discover Nano (2025) 20:18 | https://doi.org/10.1186/s11671-024-04163-w 1 Introduction Cancer is one among the major global health problems affecting millions of the population each year. According to World Health Organization, the mortality and incidence data for 2020 was recorded as 10 million deaths due to cancer [1] while in India, according to the consolidated report by the National Cancer Registry programme for the year 2020 the estimated number of people affected with cancer are around 2.7 million estimating 1 in 9 people to have the risk of developing cancer before the age of 75 [2]. Bone tumor constitutes only 1% of the overall cancer diagnosis but with rapid aggressive cancer spread, high mortality rate, concurrent recurrence, high disability and low 5-year survival rate it poses a lethal threat to the human population. Osteosarcoma (OS) is one among the most prevalent primary malignant bone tumors affecting children and teenagers, with an occurrence of more than 3.4 per million in a year [3]most often located at the metaphysis of long bones, in the distal femur, tibia and humerus also found in the diaphysis in some cases. The clinical symptoms of bone tumor initiate with severe pain, swelling of the affected bone site, hypercalcemia and pathological fracture [4].The other common bone tumors differing based on their bone tissue origin are chondrosarcoma, Ewing tumor and chordomas; the prognosis for patients with bone tumor depends on many factors including the type, location of tumor, stage of growth of the tumor tissue, metastasis position during diagnosis, tertiary health conditions of the person and response to medication [5–7].The conventional treatment in the current clinical scenario comprises of surgical resection accompanied adjuvant therapy with chemotherapy, radiotherapy or targeted therapy; in an aggressive metastatic state or condition, amputation of the diseased site [8]. The complication and heterogeneity of bone tumors calls for a better understanding to improve therapeutic strategies, to reduce recurrence, and improve the survival condition after treatment. The different FDA approved drugs used in the chemotherapy health care systems are paclitaxel, Adriamycin, cisplatin, Denosumab, doxorubicin which have been crucially used for chemotherapeutic management of the disease which is the only solution despite the facts of its damage to normal cells, multidrug resistance and effective tumor targeting [9]. Accompanying the conventional therapies there are also emerging therapies like immunotherapy [10], PDT (Photo Dynamic Therapy) [11], PTT (Photo thermal therapy) [12], MHT (Magnetic hyperthermia therapy) [13], Gene therapy [14] and CDT (Chemo dynamic therapy) [15] which are being explored towards cancer for a much more efficient solution [16]. The emergence of nanotechnology has given a ray of hope resulting to bridge the plentiful clinical challenges faced with conventional therapies. The use of inorganic magnetic nanomaterials in therapeutic and diagnostic applications as drug delivery systems, targeting and contrast agents, to reduce side effects and improve the treatment efficiency for tumors has been researched extensively and during the past decades. Progressively these magnetic nanomaterials show advantages over the conventional treatment strategies. One of the remarkable study of iron oxide nanoparticles(IONPs) which are also called super paramagnetic iron oxide nanoparticles (SPIONS) for cancer treatment has emerged as an efficient representative, identified to have potential features particularly to target cancer cells and provide an external stimuli without damage to cells with commendable contribution in precision medicine [17]. Its applications has been well explored over the recent years with a subsequent interest towards the field of cancer research for targeted drug delivery, gene targeting, hyperthermia, and magnetic resonance imaging. [18]. Since they are non-toxic to cells and possess the ability to exhibit super-paramagnetism property it makes them very attractive to researchers to target the cancer cells from a magnetic perspective externally which could open new doors to non-invasive procedures. A few other prominent areas where iron oxide nanopar (...truncated)