Ultrasound‑Enhanced Drug Delivery: Applications and Therapeutic Advances

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2760

Editors


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Guest Editor
Department of Physics, Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, London SM2 5NG, UK
Interests: ultrasound therapy; thermal ablation; cavitation; ultrasound bio-effects; cancer research; vascular occlusion
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Guest Editor
Department of Physics, Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, London SM2 5NG, UK
Interests: HIFU; histotripsy; ultrasound therapy; cancer treatment; ablation; biological effects; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The intersection of therapeutic ultrasound with advanced drug delivery systems has emerged as a powerful platform for improving treatment precision and efficacy. Beyond traditional imaging, ultrasound modalities, such as high-intensity focused ultrasound, histotripsy, ultrasound-induced cavitation, and sonoporation, are now being harnessed to enhance permeability across biological barriers, including the blood–brain barrier and tumor vasculature.

Microbubbles and ultrasound-responsive nanocarriers (e.g., liposomes and nanoparticles) enable localized release upon acoustic activation, significantly boosting therapeutic payload delivery while minimizing systemic toxicity. Innovations such as in situ drug synthesis via ultrasound-triggered pro-drug carriers and integration with theragnostic approaches are demonstrating substantial advances in oncology, neurology, and immunomodulation.

The goal of this Special Issue is to spotlight cutting-edge research that spans mechanistic studies, carrier design, modeling, preclinical investigations, and early-phase clinical trials. Contributions are encouraged in areas that include

  • Ultrasound-mediated disruption to barriers to drug delivery (e.g., tumor microenvironment, BBB).
  • Development of smart acoustic carriers for targeted delivery and controlled release.
  • Sonodynamic and immune-enhancement therapies.
  • Real-time image guidance and monitoring.
  • Novel techniques such as ultrasound-activated drug synthesis or the intralesional delivery method.
  • Basic biology, immunology, and physics investigations highlighting the effect of ultrasound on key signaling mechanisms.

We aim to connect fundamental insights with translational impact, supporting submissions that demonstrate improved pharmacokinetics/pharmacodynamics, safety profiles, and therapeutic outcomes leading toward clinical adoption.

We invite original research, reviews, or communication articles that contribute to the evolving landscape of ultrasound-enhanced drug delivery. We look forward to your innovative work shaping the future of precision therapeutics.

Prof. Dr. Gail Ter Haar
Dr. Petros Mouratidis
Guest Editors

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Keywords

  • therapeutic ultrasound
  • high‑intensity focused ultrasound (HIFU)
  • focused ultrasound surgery (FUS)
  • histotripsy
  • sonoporation
  • sonodynamic therapy
  • drug delivery
  • microbubbles
  • nanoparticles
  • cancer
  • neurodegenerative conditions

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Published Papers (2 papers)

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Research

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23 pages, 106862 KB  
Article
Perfluoropentane Phase-Change Nanodroplets for Focused Ultrasound-Enhanced Drug Penetration and Immune Response
by Kichang Shin, Dongyeon Kim, Hyungwon Moon, Keunho Son, Mi Jeong Kim and Hak Jong Lee
Pharmaceutics 2026, 18(3), 302; https://doi.org/10.3390/pharmaceutics18030302 - 27 Feb 2026
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Abstract
Background/Objectives: Solid tumors are characterized by a dense stromal structure and heterogeneous microenvironments that limit intratumoral drug penetration and contribute to immune exclusion. We developed perfluoropentane (PFP)-based phase-change nanodroplets (IMP700) and aimed to identify focused ultrasound (FUS) parameters that enhance cavitation and [...] Read more.
Background/Objectives: Solid tumors are characterized by a dense stromal structure and heterogeneous microenvironments that limit intratumoral drug penetration and contribute to immune exclusion. We developed perfluoropentane (PFP)-based phase-change nanodroplets (IMP700) and aimed to identify focused ultrasound (FUS) parameters that enhance cavitation and sonoporation to improve drug delivery and immune engagement in tumor models. Methods: IMP700 was prepared as lipid-shelled PFP nanodroplets and physicochemically characterized. Acoustic droplet vaporization (ADV), echogenicity, and cavitation were evaluated in vitro and in vivo using ultrasound imaging and cavitation analysis under varying FUS parameters, including acoustic intensity, duty cycle, and pulse repetition frequency (PRF), in PANC-1 xenograft tumors. Sonoporation was assessed by co-administering an ultrasound-responsive doxorubicin liposome (IMP301), and intratumoral drug distribution was analyzed by confocal imaging. Immune responses were evaluated in a syngeneic 4T1 tumor model by quantifying CD8+ T-cell infiltration after repeated treatments. Results: IMP700 exhibited nanoscale size and high PFP encapsulation efficiency and underwent ADV with increased echogenicity and intensity-dependent cavitation. In vivo, a 2% duty cycle and 10 Hz PRF produced strong and reproducible cavitation. Under these conditions, IMP700 markedly increased inertial cavitation and enhanced intratumoral drug penetration compared to FUS alone. Combined IMP700 and FUS treatment also increased intratumoral CD8+ T-cell infiltration. Conclusions: IMP700 amplifies FUS-induced cavitation, improves sonoporation-mediated drug delivery, and promotes CD8+ T-cell infiltration, which supports the use of FUS-activated nanodroplets as a strategy to overcome stromal and immunological barriers in solid tumors. Full article
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Review

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17 pages, 2583 KB  
Review
Ultrasound-Enhanced Drug Delivery in Pediatric Neuro-Oncology: A New Therapeutic Strategy
by Elora Weber, Christian A. Smith, Cynthia Hawkins, Uri Tabori, Peter B. Dirks and James T. Rutka
Pharmaceutics 2026, 18(5), 576; https://doi.org/10.3390/pharmaceutics18050576 - 7 May 2026
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Abstract
Pediatric brain tumors are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumor types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, and neuropathological and molecular genetic [...] Read more.
Pediatric brain tumors are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumor types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, and neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumors with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood–brain barrier (BBB), which serves as a protective mechanism for neuronal homeostasis. The BBB primarily comprises microvascular endothelial tight junctions. Controlling BBB permeability to allow for therapeutics to cross and combat brain tumors is now possible using MR-guided focused ultrasound (MRgFUS). In this approach, microbubbles are administered intravenously prior to MRgFUS BBB disruption at the targeted tumor site in the brain. In the presence of MRgFUS, the microbubbles in the brain capillaries oscillate and temporarily disrupt the BBB, enabling systemically administered chemotherapy drugs to cross at the targeted site. In this review, we provide evidence supporting the use of MRgFUS BBB disruption to treat brain tumors in animal models and in ongoing human clinical drug trials. We conclude with efforts to harness the potency of the immune system using MRgFUS against pediatric brain tumors. Full article
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