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Adaptive smart biomaterials to overcome metastatic tumor microenvironment heterogeneity: Theranostic strategies and clinical translation roadmaps
Aqsa Mehreen
Imran Khan Yousafzai
Maryam Faiz
Hawaida Ahmed
Characterization and Application of Nanomaterials 2025, 8(4), 11919; https://doi.org/10.24294/can11919
Submitted:14 Nov 2025
Accepted:20 Nov 2025
Published:24 Nov 2025
Abstract

Over 90% of cancer-related mortality worldwide is due to metastatic disease since the dynamic tumor microenvironment poses huge challenges in preventing the spread of metastatic cancer. Introducing the advent of advanced biomaterials and their swift evolution, this review highlights the great potential of innovative biomaterials to tackle the metastatic tumor environment. Focusing on four distinct categories of biomaterial systems, the action mechanism of biomaterials utilized in anti-tumor therapy is explained in detail: 1. Nanoplatforms sensitive to biochemical cues, including pH, redox, and enzymes, are known as stimuli-responsive nanoplatforms that react according to their environment, 2. Smart nanoplatforms changing their morphology to penetrate impermeable physical barriers at the tumor site, 3. Ingenious biomaterial participating in tumor normalization, and 4. Nanoplatforms with real-time theranostic capabilities due to an innate feedback-loop mechanism. Ingeniously structured biomaterials with extensive evidence in preclinical efficacy encourage their inclusion in metastatic tumor therapy. However, their utilization in medical settings is prevented due to various challenges. Impractical manufacturing costs, regulatory and safety issues, as well as large-scale production, are major challenges restraining their widespread use. A concrete framework is proposed in this review to accelerate the biomaterial structure standardization process, following GMP and other regulatory guidelines, to implement biomaterial-based tumor diagnostics and therapies. Since incorporating advancing technologies in tumor therapy, such as AI-driven, autonomous biomaterial structures or patient-specific tumor models, would enable confronting the proliferating metastatic tumor cases.

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