Aug 2026· Polymer Science & Technology· 0 citations· 113 references
TL;DR
Development of polymer-enabled improvements in contrast, targeting, and molecular specificity establish ultrasound-responsive polymers as promising foundations for next-generation precision medicine.
Abstract
Ultrasound-responsive polymers have emerged as a powerful platform for precision medicine by enabling the conversion of external acoustic energy to controlled physicochemical and biological responses. This review summarizes recent advances in the design and application of such systems, highlighting their evolution from passive drug carriers to multifunctional platforms integrating therapy, imaging, and immunomodulation. We first highlight the ultrasound-triggered drug release strategies, including mechanically induced bond cleavage, disruption of noncovalent interactions, and reactive oxygen species (ROS)-mediated degradation, which enable spatiotemporal control over therapeutic delivery. We also discuss sonodynamic therapy, where polymer sonosensitizers generate cytotoxic ROS, representing a shift from indirect drug delivery to a direct therapeutic intervention. Advances in ultrasound and photoacoustic (PA) imaging are further highlighted, emphasizing polymer-enabled improvements in contrast, targeting, and molecular specificity. In particular, long-wavelength PA imaging, molecular structure engineering, and biomarker-activatable probes have significantly enhanced the imaging depth and precision. Finally, we discuss key challenges for clinical translation and outline future directions toward intelligent, self-adaptive systems and closed-loop theranostic platforms. These developments establish ultrasound-responsive polymers as promising foundations for next-generation precision medicine.
Sonodynamic therapy (SDT) utilizes ultrasound to activate sonosensitive agents, generating reactive oxygen species (ROS) within tumor cells to induce oxidative damage. The advantages of ultrasound, such as deep tissue penetration, non-invasiveness, and spatial controllability, make it a promising candidate for cancer treatment. However, its practical application is still limited by factors such as low in vivo delivery efficiency, tumor hypoxia and antioxidant defense mechanisms, insufficient conversion of immunogenic cell death into durable anti-tumor immunity, and the lack of standardized ultrasound parameters, ROS quantification, and material quality control. Near-infrared II (NIR-II) conjugated polymers offer a promising platform because their tunable π-conjugated backbone, stable nano-assembly structure, organic composition, and modular design allow for the integration of imaging, ultrasound-triggered ROS generation, drug delivery, and immune microenvironment modulation into a single system. This article reviews recent research progress in NIR-II conjugated polymer SDT for cancer treatment. First, the physicochemical mechanisms, ROS generation pathways, and validation methods of sonodynamic therapy (SDT) are discussed, and conjugated polymers are compared with traditional small molecule and inorganic/semiconductor sonosensitive agents. This paper analyzes the significance of near-infrared II (NIR-II) imaging for surgical drug delivery (SDT) in terms of drug tracing, tumor localization, and therapeutic window. It further discusses the molecular design, aggregation state regulation, degradability, nanoassembly, delivery, and translational applications of organic conjugated polymer materials. Tumor-related barriers, including hypoxia, delivery obstacles, immunosuppressive microenvironment, and metabolic disorders, are then analyzed, and representative combined therapy strategies involving oxygen supply, chemotherapy, immunotherapy, myeloid cell remodeling, and matrix modulation are summarized. Finally, the challenges faced by materials in NIR-II signal quantification, ROS validation, long-term biosafety, ultrasound dosimetry, and clinical translation are discussed.
Ultrasound (US), known for its non-invasive nature and high tissue penetration, has demonstrated remarkable potential in medical diagnostic imaging and tumor therapy. Nanocarriers, through the use of nanomaterials, has exhibited significant advantages in targeted drug delivery, improving bioavailability and reducing side effects. The integration of these two technologies enables sensitive diagnose, precise drug release under ultrasound activation, enhancing comprehensive therapeutic efficacy, which make ultrasound-driven nanocarriers a hotspot in the field of tumor diagnosis and treatment. Therefore, this review provides a comprehensive overview of the biophysical effects of ultrasound and the advantages of ultrasound-driven nanocarriers. Subsequently, it systematically summarizes the classification of ultrasound-based nanocarriers, including both organic and inorganic carriers. Furthermore, the article elaborates in detail on the applications of ultrasound-mediated nanocarriers systems in oncology, including ultrasound-enhanced nanocarriers systems for imaging applications, sonodynamic therapy (SDT), and high-intensity focused ultrasound (HIFU). Finally, the work conducts an in-depth analysis of the challenges hindering clinical translation and offers perspectives on future research directions.
Functionalized coacervates, a type of nanomaterial inspired by biomolecular condensation, have emerged as an important research direction in biomedicine, particularly in cancer therapy. These membraneless structures formed by liquid-liquid phase separation (LLPS) self-assembly have high drug-loading capacity, favorable biocompatibility, and tunable responsiveness to tumor microenvironment (TME) cues. This programmability enables targeted delivery and controlled release. This review summarizes the latest progress in the design and therapeutic application of functionalized coacervates in cancer therapy. We first introduce the construction strategies, including basic driving forces, material platforms, and advanced architectures. Then, we explain the mechanisms that enhance therapeutic efficacy and reduce toxicity, including enhanced loading and stability, improved pharmacokinetics and tumor accumulation, and enhanced intracellular delivery that can overcome multidrug resistance (MDR). We also discuss spatiotemporal release triggered by TME cues, such as acidity, redox, or enzymatic activity. Next, we highlight applications in chemotherapy, nucleic acid delivery, cancer immunotherapy, multimodal combination therapy, and emerging directions. Finally, we discuss translational challenges and outline future research directions. We aim to provide a coherent framework for researchers and to facilitate the development and clinical translation of coacervate-based therapeutics.
Pu-Ge Yu, Qian-Qian Li, Jiaming Wang et al.· Small· 0 citations
Cancer remains a major global health challenge, and the limitations of conventional therapies, including systemic toxicity, drug resistance, and poor tumor selectivity, continue to drive the development of advanced nanomedicine strategies. In this context, nanocarriers offer promising opportunities to improve pharmacokinetics, enhance tumor accumulation, and enable controlled or stimuli-responsive drug release. Among them, inorganic nanoparticles (NPs) have gained considerable attention because of their structural stability, tunable surface chemistry, and multifunctional capabilities. Their performance depends on a structure–property–function relationship in which composition, morphology, porosity, degradability, and surface characteristics strongly influence interactions at the nano–bio interface. This review examines the main classes of nanoplatforms currently explored for cancer therapy, including inorganic, polymeric, lipid-based, and hybrid organic–inorganic systems. Particular attention is given to the trade-offs that define each platform in terms of loading capacity, biodegradability, multifunctionality, and translational potential. The discussion also highlights the role of predictive biological models, emphasizing that 3D spheroids, organoids, and organ-on-chip systems provide more realistic insights than conventional 2D assays for evaluating tumor penetration and microenvironment-responsive delivery. In addition, the review considers emerging directions in AI-guided nanoparticle engineerization design and natural-compound-based nanomedicines, both of which are expanding the therapeutic landscape. Overall, the field is moving toward more integrated, application-specific, and clinically translatable nanomedicine platforms capable of addressing the complex biological barriers of cancer treatment.
C. Boncristiani, F. Baldassarre, Khadija Eddahaoui et al.· Materials· 0 citations
This review critically evaluates the design parameters of biopolymer delivery systems, focusing on the optimization of particle size and drug loading capacity and addresses key translational hurdles, including the biological limitations of active targeting and safety concerns like complement activation-related pseudoallergy.
