Orchestrating Tumor Microenvironment Modulation Through Artificial Intelligence-Driven Nanoparticle Systems for Precision Cancer Therapeutics

Trends in Immunotherapy

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Orchestrating Tumor Microenvironment Modulation Through Artificial Intelligence-Driven Nanoparticle Systems for Precision Cancer Therapeutics

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https://doi.org/10.54963/ti.v9i4.1284
Sivanandam, S., Efgivia, M. G., K, A., Manikandan, S., Reddy, C. P., & Devi, Y. Y. (2025). Orchestrating Tumor Microenvironment Modulation Through Artificial Intelligence-Driven Nanoparticle Systems for Precision Cancer Therapeutics. Trends in Immunotherapy, 9(4), 104–119. https://doi.org/10.54963/ti.v9i4.1284
Volume 9 Issue 4 (December 2025): In Progress
Copyright (c) 2025 S. Sivanandam, Mohammad Givi Efgivia, Ashok K, S Manikandan, C.S. Preetham Reddy, Ykuntam Yamini Devi
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Authors

  • S. Sivanandam

    Department of Biomedical Engineering, Saveetha Engineering College, Chennai, Tamil Nadu 602105, India
  • Mohammad Givi Efgivia

    Information Systems and Technology, Muhammadiyah University Prof. Dr. Hamka, Kota Jakarta Selatan, DKI Jakarta 12130, Indonesia
  • Ashok K

    Electronics and Communication Engineering, The National Institute of Engineering, Manandavadi Road, Mysuru, Karnataka 570008, India
  • S Manikandan

    PSCMR College of Engineering and Technology, Vijayawada, Andhra Pradesh 520001, India
  • C.S. Preetham Reddy

    Department of Electronics and Communication Engineering, K L Deemed to be University, Guntur, Andhra Pradesh 522302, India
  • Ykuntam Yamini Devi

    Department of Electronics & Communication Engineering, Aditya University, Surampalem, Andhra Pradesh 533437, India

Received: 30 May 2025; Revised: 19 June 2025; Accepted: 27 June 2025; Published: 31 October 2025

The tumor microenvironment (TME) is an environment that affects the growth, progression, and resistance of the tumor. AI is already transformational in the process of comprehending and attacking the TME. Using datasets with many more variables and different aspects, AI models can predict tumor behavior with greater precision than conventional techniques. In this work, the polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles coated with magnesium fluoride (MgF2) and loaded with L-arginine have been developed to modulate the immunity in tumors using nitric oxide (NO). Designed to be released near the TME, PLGA-MgF2 regulates the release of NO, producing an improvement in immune responses against cancer cells. Plasma-polymer coating of PLGA-MgF2 nanoparticles showed an average size of 150 nm with MgF2 shell thicknesses of 12–14 nm and L-arginine loads of 72–75%. The concentrations of NO did not change under the acidic tumor-like conditions, and the concentration was between 25 and 30 µM in the first 48 hours. Transmission electron microscopy (TEM) showed 75–120 particles per square micrometer in the tumor, and the immune cell infiltration increased by 35–45%, and the hypoxia in the tumor decreased by 30–36%. The deep neural networks and support vector machines reached 85–95% accuracy in tumor response classification using AI. The therapy led to 60% augmentation of T-cell activation, 85% tumor growth retardation, 4-fold elevation of the M1/M2 ratio, and 45% longer survival.

Keywords:

Tumor Microenvironment (TME) Artificial Intelligence Nanoparticles Magnesium Fluoride (MgF₂) L-Arginine Immunomodulation

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