Advances in green-synthesized magnetic nanoparticles for targeted cancer therapy: mechanisms, applications, and future perspectives

In the paper

“This decreases the environmental burden for nanoparticle production and improves biocompatibility making them more suitable than synthesis processes [6, 9].”

What the sources say

• ?Not checked — no full text of the sourcecites [6] Kirubakaran D, et al. A comprehensive review on the green synthesis of nanoparticles: advancements in biomedical and environmental applications. Biomed Mater Devices. 2025. https://doi.org/10.1007/s44174-025-00295-4. source
• ?Not checked — no full text of the sourcecites [9] Reddy LH, et al. Magnetic nanoparticles: design and characterization, toxicity and biocompatibility, pharmaceutical and biomedical applications. Chem Rev. 2012;112(11):5818–78. source

In the paper

“Green synthesis utilizes biological agents, such as plant extracts, microorganisms, and natural enzymes that can produce nanoparticles over mild, environmentally friendly conditions [8].”

What the sources say

• ?Not checked — no full text of the sourcecites [6] Kirubakaran D, et al. A comprehensive review on the green synthesis of nanoparticles: advancements in biomedical and environmental applications. Biomed Mater Devices. 2025. https://doi.org/10.1007/s44174-025-00295-4. source
• ?Not checked — no full text of the sourcecites [7] Getahun YW, et al. Green synthesized superparamagnetic iron oxide nanoparticles for water treatment with alternative recyclability. J Mol Liq. 2022;356:118983. source
• Check pendingcites [8] Bhardwaj B, et al. Eco-friendly greener synthesis of nanoparticles. Adv Pharm Bull. 2020;10(4):566. source

In the paper

“magnetic nanoparticles (MNPs) are of particular interest because of their unique magnetic properties, surface modifiability, and the ability to interact with external magnetic fields [3]. These factors also make MNPs suitable for many applications, such as targeted drug delivery, imaging, diagnostics, and hyperthermia treatments [4].”

What the sources say

• Check pendingcites [3] Wong IY, Bhatia SN, Toner M. Nanotechnology: emerging tools for biology and medicine. Genes Dev. 2013;27(22):2397–408. source
• Check pendingcites [4] Comanescu C. Recent advances in surface functionalization of magnetic nanoparticles. Coatings. 2023;13(10):1772. source

In the paper

“Iron-oxide NPs (Fe3O4 or γ-Fe2O3) are generally recognized as safe (GRAS) by the FDA when produced under controlled conditions. They degrade to natural iron ions that can be included in the normal metabolic processes in the body [71].”

What the sources say

• Check pendingcites [71] Vasić K, Knez Ž, Leitgeb M. Multifunctional iron oxide nanoparticles as promising magnetic biomaterials in drug delivery: a review. J Funct Biomater. 2024;15(8):227. source

In the paper

“MNP synthesized through green methods has shown excellent performance in such tests, usually more than 90% of the cell's viability at high concentrations. This low toxicity is attributed to the lack of harmful chemicals and the lack of natural detergents used in the synthesis process [33].”

What the sources say

• ?Not checked — no full text of the sourcecites [33] Chen W, et al. One-step green synthesis of hybrid Fe-Mn nanoparticles: methodology, characterization and mechanism. J Clean Prod. 2022;363:132406. source

In the paper

“Drug delivery systems (DDS), including magnetic nanoparticles (MNPs), possess inherent limitations that diminish their efficacy as therapeutic options. Challenges include unpredictable pharmacokinetics, rapid elimination, and nonspecific distribution [37].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [37] Prieložná J, Mikušová V, Mikuš P. Advances in the delivery of anticancer drugs by nanoparticles and chitosan-based nanoparticles. Int J Pharmaceutics: X. 2024;8:100281.

In the paper

“Nonselective activity leads to side effects, including fatigue, nausea, immunosuppression, alopecia, and opportunistic infections. Such side effects not only reduce the patient’s quality of life but may also limit the dose and duration of treatment, compromising its overall effectiveness [15].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [15] Cairo AN, et al. Nonspecific prophylaxis of influenza. Non-specific prevention of influenza and SARS What is non-specific prevention Nonspecific prevention of influenza and acute respiratory viral infections with Anaferon in the Moscow region.

In the paper

“Resistance to chemotherapy, both intrinsic and acquired, is another major hurdle [17]. Tumor cells may develop mechanisms to pump out drugs (efflux), repair DNA damage, or activate survival pathways, making them less responsive to treatment [18].”

What the sources say

• Check pendingcites [17] Gu Y, et al. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. Mol Biomed. 2025;6(1):2. source
• ?Not checked — no full text of the sourcecites [18] Haider T, et al. Drug resistance in cancer: mechanisms and tackling strategies. Pharmacol Rep. 2020;72(5):1125–51. source

In the paper

“With MNPs, the surface-to-volume ratio will increase also increasing its reactivity, allowing for easy surface behavior and increasing the number of functional groups on the surface making MNP settling a versatile platform for biomedical applications [56].”

What the sources say

• Check pendingcites [56] Ahmed MM, Abu-Elsaad N Exploring the Magnetic behavior of ferrites: from diamagnetism to superparamagnetism. arXiv preprint arXiv:2406.10599. 2024. source

In the paper

“With iron-oxide-based materials, we typically expect to be able to synthesize materials like iron oxides magnetite (Fe3O4) or maghemite (γ-Fe2O3) [55].”

What the sources say

• ?Not checked — no full text of the sourcecites [55] Busti ND, Parra R, Sousa M. Góes, Synthesis, properties, and applications of iron oxides: versatility and challenges. In: Functional properties of advanced engineering materials and biomolecules. Springer; 2021. p. 349–85. source

In the paper

“Their magnetic core provides an external field-guided navigation which can facilitate selective targeting of the tumor and delivery of chemotherapeutic agents directly to the tumor area while limiting exposure to the body which minimizes side effects [11].”

What the sources say

• Check pendingcites [11] Huang J, et al. Magnetic nanoparticle facilitated drug delivery for cancer therapy with targeted and image-guided approaches. Adv Funct Mater. 2016;26(22):3818–36. source

In the paper

“The benefits include low costs, ambient temperature operations, and minimum processing after hypothesis [45].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [45] Yusoff AHM, Salimi MN, Jamlos MF. A review: synthetic strategy control of magnetite nanoparticles production. Adv Nano Res. 2018;6(1):1.

In the paper

“High crystallinity ensures uniformity in magnetic reaction, which is important for frequent performance in applications, such as MRI contrast improvement or magnetic drug correction [66].”

What the sources say

• ?Not checked — no full text of the sourcecites [66] Wang S, et al. Magnetic nanostructures: rational design and fabrication strategies toward diverse applications. Chem Rev. 2022;122(6):5411–75. source

In the paper

“Moreover, some tumors are radioresistant and may not respond adequately even at high radiation doses, increasing the risk of recurrence [19].”

What the sources say

• Check pendingcites [19] Wu Y, et al. Molecular mechanisms of tumor resistance to radiotherapy. Mol Cancer. 2023;22(1):96. source

In the paper

“DDS have been specifically established to tackle these issues, as it utilizes these issues as means of targeting tumor sites, which provides efficiency, safety, and site-specific drug delivery [28]. It brings about high local drug concentrations, extended drug retention on tumors, and minimal off-target side effects.”

What the sources say

• Check pendingcites [26] Ezike TC, et al. Advances in drug delivery systems, challenges and future directions. Heliyon. 2023. https://doi.org/10.1016/j.heliyon.2023.e17488. source
• Check pendingcites [27] Crawford S. Is it time for a new paradigm for systemic cancer treatment? Lessons from a century of cancer chemotherapy. Front Pharmacol. 2013;4:68. source
• Not checked yetcites [28] Liu D, et al. The smart drug delivery system and its clinical potential. Theranostics. 2016;6(9):1306. source

In the paper

“Nanoparticles exhibit diverse dimensions, possess distinct surface characteristics, and deliver pharmaceuticals at various rates. This complicates the attainment of consistent outcomes and hinders the replication and regulation of drug release [38].”

What the sources say

• Check pendingcites [38] Khan I, Saeed K, Khan I. Nanoparticles: properties, applications and toxicities. Arab J Chem. 2019;12(7):908–31. source

In the paper

“Their stability in biological environments is improved through coatings, such as polyethylene glycol (PEG), dextran, or silica, which prevent aggregation and improve dispersion. These coatings further help in reducing immunogenic responses [59].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [59] Chen Y, Su YC, Roffler SR. Polyethylene glycol immunogenicity in nanomedicine. Nat Rev Bioeng. 2025;10:1–9.

In the paper

“Hypoxic regions within tumors, for example, are less susceptible to radiation and certain chemotherapies, leading to incomplete eradication and eventual relapse [22].”

What the sources say

• Not checked yetcites [22] Jing X, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 2019;18(1):157. source

In the paper

“Another essential attribute of MNP-DDS is its multipurpose. Aside from drug delivery, MNP can also be used for clinic imaging such magnetic resonance imaging (MRI) and magnetic hyperthermia. This double role of therapy and diagnosis is known as 'Therrnostics', which is a rapidly growing area in personal medicine [30].”

What the sources say

• Not checked yetcites [30] Estelrich J, et al. Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery. Int J Mol Sci. 2015;16(4):8070–101. source

In the paper

“In addition, the plant-based synthesis methods are easily scalable and compatible with industrial needs [46].”

What the sources say

• ?Not checked — no full text of the sourcecites [46] Yoon TP, Ischay MA, Du J. Visible light photocatalysis as a greener approach to photochemical synthesis. Nat Chem. 2010;2(7):527–32. source

In the paper

“Biocompatibility is one of the most important criteria for clinical use of MNP. Since these particles intend to be used in biological systems, their interaction with cells, tissues, and organs should not induce side effects, such as inflammation, toxicity, or immune rejection [69].”

What the sources say

• Check pendingcites [69] Nowak-Jary J, Machnicka B. Comprehensive analysis of the potential toxicity of magnetic iron oxide nanoparticles for medical applications: cellular mechanisms and systemic effects. Int J Mol Sci. 2024;25(22):12013. source

In the paper

“Due to the superparamagnetic properties of these types of materials, they will respond to an external magnetic field (i.e., show magnetism) but will not possess any magnetism once removed.”

What the sources say

• Check pendingcites [56] Ahmed MM, Abu-Elsaad N Exploring the Magnetic behavior of ferrites: from diamagnetism to superparamagnetism. arXiv preprint arXiv:2406.10599. 2024. source

In the paper

“Diverse biological factors, such as plant extracts or microbes, can influence the size, charge, and stability of particles. These discrepancies can alter the drug's release and efficacy, so it is crucial to standardize green synthesis methodologies for medicinal applications [54].”

What the sources say

• Check pendingcites [54] Jahangirian H, et al. A review of drug delivery systems based on nanotechnology and green chemistry: green nanomedicine. Int J Nanomed. 2017. https://doi.org/10.2147/IJN.S127683. source

In the paper

“When it comes to synthesis, parameters, such as temperature, pH, precursor initial concentration, and response time, can be good for controlling these structural properties. Techniques, such as coprecipitation, thermal decomposition, and hydrothermal synthesis, are widely used to achieve the desired structural and magnetic features [67].”

What the sources say

• Check pendingcites [67] Li Z, et al. An overview of synthesis and structural regulation of magnetic nanomaterials prepared by chemical coprecipitation. Metals. 2023;13(1):152. source

In the paper

“Bioactive compounds not only reduce ions but also cap particles to prevent agglomeration and improve stability. It is consistent with the principles of green chemistry and provides benefits in terms of safety, costs, and purposes in biomedical regions [52].”

What the sources say

• Check pendingcites [52] Zabot GL, et al. Encapsulation of bioactive compounds for food and agricultural applications. Polymers. 2022;14(19):4194. source

In the paper

“Surgical intervention, while effective in removing localized tumors, is limited by tumor accessibility and the risk of incomplete resection. In cases of metastatic disease, surgery is often not viable, and recurrence is common due to residual cancer cells or micrometastases that evade detection [20].”

What the sources say

• Check pendingcites [20] O’Sullivan GC, et al. Micrometastases: marker of metastatic potential or evidence of residual disease? Gut. 1997;40(4):512–5. source

In the paper

“High-energy radiation can damage surrounding healthy tissues and cause long-term side effects, such as fibrosis, secondary malignancies, and organ dysfunction.”

What the sources say

• Check pendingcites [19] Wu Y, et al. Molecular mechanisms of tumor resistance to radiotherapy. Mol Cancer. 2023;22(1):96. source

In the paper

“Traditional chemical and physical methods often require high temperatures, dangerous reagents, and detailed layouts, which can be energy-intensive and environmentally harmful [42].”

What the sources say

• Check pendingcites [42] Dallinger D, Gutmann B, Kappe CO. The concept of chemical generators: on-site on-demand production of hazardous reagents in continuous flow. Acc Chem Res. 2020;53(7):1330–41. source

In the paper

“Because of their small size, they can penetrate tissues deeply allowing for accumulation to the tumor site by enhanced permeability and retention effect (EPR) [10].”

What the sources say

• ?Not checked — no full text of the sourcecites [10] De Matteis V, et al. Green synthesis of nanoparticles and their application in cancer therapy. In: Green synthesis of nanoparticles: applications and prospects. Springer; 2020. p. 163–97. source

In the paper

“Green synthesis of MNPs has proven to be a permanent and environmentally friendly approach in nanotechnology. It benefits from naturally derived materials and biological processes to produce nanoparticles with toxicity and increased biocompatibility [41].”

What the sources say

• ?Not checked — no full text of the sourcecites [41] El-Khawaga AM, Zidan A, El-Mageed AIAA. Preparation methods of different nanomaterials for various potential applications: a review. J Mol Struct. 2023;1281:135148. source

In the paper

“Cytotoxicity is often evaluated through in vitro analyses using human and animal cell lines. These tests consider viability, oxidative stress, apoptosis, and membrane integrity after exposure to nanoparticles [72].”

What the sources say

• Check pendingcites [72] Awashra M, Młynarz P. The toxicity of nanoparticles and their interaction with cells: an in vitro metabolomic perspective. Nanoscale Adv. 2023;5(10):2674–723. source

In the paper

“One challenge in clinical translation is the long-term fate of nanoparticles. Biodegradation rates, excretion pathways, and possible interactions with other medications must be fully understood [73].”

What the sources say

• ?Not checked — no full text of the sourcecites [73] Zheng C, Li M, Ding J. Challenges and opportunities of nanomedicines in clinical translation. Bio Integr. 2021;2(2):57. source

In the paper

“Traditional carriers lack intrinsic imaging properties and often require separate agents for diagnostics [91].”

What the sources say

• Check pendingcites [91] Woźniak M, et al. Molecular imaging and nanotechnology—emerging tools in diagnostics and therapy. Int J Mol Sci. 2022;23(5):2658. source

In the paper

“These coatings confirm that the material is released in the tumor microenvironment, while traditional carriers would have the potential for leaks and off-target effects [89].”

What the sources say

• Check pendingcites [89] Wang L, et al. Micro-nanocarriers based drug delivery technology for blood-brain barrier crossing and brain tumor targeting therapy. Small. 2022;18(45):2203678. source

In the paper

“MNPs, particularly iron-oxide nanoparticles, provide contrast for magnetic resonance imaging (MRI), enabling simultaneous therapy and monitoring—known as theranostics [92].”

What the sources say

• Check pendingcites [92] Rahman M. Magnetic resonance imaging and iron-oxide nanoparticles in the era of personalized medicine. Nanotheranostics. 2023;7(4):424. source

In the paper

“To mitigate this, surface modifications such as PEGylation or the use of stabilizing agents like dextran have been employed, but these solutions are not universally effective [101].”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Obasi CC, Banigo AT, Chapter 10-Surface modifications of nanoparticles and their suitability for studying gastrointestinal diseases, in Nano-Bio-Medicine for Gastrointestinal Diseases, Chaturvedi V et al. Editors. 2026. Academic Press. 293–310. source

In the paper

“MNPs impart a multimodal mechanism of action in cancer cells, that is, delivery of drugs, apoptosis induction, cellular homeostasis disruption, and thermal ablation as an agent. These mechanisms can occur individually and/or in concert to improve efficiency and limit drug resistance.”

In the paper

“These findings show how MNPs can increase precise oncology by increasing medical effect, reducing toxicity and lightweight real-time monitoring of treatments.”

In the paper

“In another study investigating paclitaxel-conjugated magnetic nanoparticles (MNPs) for the treatment of ovarian cancer, polyethylene glycol (PEG) was utilized to coat the MNPs. This prolonged their presence in the body and prevented premature excretion.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [83] Ejeta BM, Das MK, Das S. Recent advances in Paclitaxel drug delivery: challenges, innovations, and future directions. Integr Biomed Res. 2024;8(8):1–13.

In the paper

“The medication was administered over a period of 72 h and remained effective long after the treatment concluded [83].”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [83] Ejeta BM, Das MK, Das S. Recent advances in Paclitaxel drug delivery: challenges, innovations, and future directions. Integr Biomed Res. 2024;8(8):1–13.

In the paper

“The MNPs containing paclitaxel were conjugated to antibodies that specifically target the CA-125 antigen, an indicator of ovarian cancer.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [83] Ejeta BM, Das MK, Das S. Recent advances in Paclitaxel drug delivery: challenges, innovations, and future directions. Integr Biomed Res. 2024;8(8):1–13.

In the paper

“When a magnetic field is used, MNPs can be moved to a specific area. This makes it easier to deliver drugs to the tumor and lessens the risk of harming healthy tissues. This process makes MNPs work better as a treatment by letting more of the drug build up at the tumor site. This improves treatment results and lowers systemic toxicity.”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites [77] Koca E. New approaches in treatment of acute myeloid leukemia. Medicine. 2022;11:914.

In the paper

“Comprehensive toxicological evaluations are necessary to ensure safety over extended periods, especially for repeated dosing regimens [69, 98].”

What the sources say

• Check pendingcites [69] Nowak-Jary J, Machnicka B. Comprehensive analysis of the potential toxicity of magnetic iron oxide nanoparticles for medical applications: cellular mechanisms and systemic effects. Int J Mol Sci. 2024;25(22):12013. source
• Check pendingcites [98] Nowak-Jary J, Machnicka B. Toxicity of magnetic nanoparticles in medicine: contributing factors and modern assessment methods. Int J Mol Sci. 2025;26(17):8586. source

In the paper

“Once inside, MNPs can let out drugs in response to changes in the environment, like changes in pH or enzyme activity. MNPs can also make reactive oxygen species (ROS), which cause oxidative stress and damage DNA, which leads to apoptosis. The figure also shows that when MNPs are exposed to an alternating magnetic field, they can cause thermal damage through magnetic hyperthermia, which works with”

What the sources say

• Check pendingcites [81] Roshani M, et al. Metal nanoparticles as a potential technique for the diagnosis and treatment of gastrointestinal cancer: a comprehensive review. Cancer Cell Int. 2023. https://doi.org/10.1186/s12935-023-03115-1. source

In the paper

“Aggregation not only alters biodistribution but also reduces therapeutic efficiency and can cause embolism or unwanted accumulation in non-target organs [96].”

What the sources say

• ?Not checked — no full text of the sourcecites [96] Cabral H, et al. Controlling the biodistribution and clearance of nanomedicines. Nat Rev Bioeng. 2024;2(3):214–32. source

In the paper

“Targeted drug delivery represents a major progress in oncology, aimed at increasing medical effect by reducing side effects. MNPs have proven to be effective carriers in this context because of their ability to locate in tumor tissue under the guidance of external magnetic fields.”

In the paper

“Once a primary tumor cell engulfs MNP(s), they can induce release of cytotoxic agents, cause intracellular signaling disruption, induce oxidative stress, and induce programmed cell death (apoptosis).”

What the sources say

• Check pendingcites [81] Roshani M, et al. Metal nanoparticles as a potential technique for the diagnosis and treatment of gastrointestinal cancer: a comprehensive review. Cancer Cell Int. 2023. https://doi.org/10.1186/s12935-023-03115-1. source

In the paper

“This aggregation leads to inconsistent biodistribution and affects their ability to effectively target tumor sites.”

What the sources say

• ?Not checked — no full text of the sourcecites [101] Obasi CC, Banigo AT, Chapter 10-Surface modifications of nanoparticles and their suitability for studying gastrointestinal diseases, in Nano-Bio-Medicine for Gastrointestinal Diseases, Chaturvedi V et al. Editors. 2026. Academic Press. 293–310. source

In the paper

“Enhanced permeability and retention (EPR) effects are potentially beneficial; nevertheless, the targeted efficiency of magnetic nanoparticles (MNPs) may vary due to the heterogeneity of malignancies [78].”

What the sources say

• ?Not checked — no full text of the sourcecites [78] Riaz S, et al. Multifunctional Magnetic Nanoparticles for Targeted Drug Delivery Against Cancer: a review of mechanisms, applications, consequences, limitations, and tailoring strategies. Ann Biomed Eng. 2025;53(6):1291–327. source

In the paper

“Active targeting strategies, such as ligand–receptor interactions, show promise in increasing selectivity, but challenges persist in achieving consistent targeting across different cancer types [102].”

What the sources say

• ?Not checked — no full text of the sourcecites [102] Imtiaz S, et al. Mechanistic study of cancer drug delivery: current techniques, limitations, and future prospects. Eur J Med Chem. 2025;290:117535. source

In the paper

“While there has been a lot of positive progress, there still remain challenges related to large-scale fabrication, stability, controlled drug release, and regulatory approval.”