Research

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18 pages, 7654 KiB

Open AccessArticle

Ultrasound-Responsive Biomimetic Superhydrophobic Drug-Loaded Mesoporous Silica Nanoparticles for Treating Prostate Tumor

by Qiaofeng Jin, Dandan Chen, Yishu Song, Tianshu Liu, Wenqu Li, Yihan Chen, Xiaojuan Qin, Li Zhang, Jing Wang and Mingxing Xie

Pharmaceutics 2023, 15(4), 1155; https://doi.org/10.3390/pharmaceutics15041155 - 05 Apr 2023

Cited by 1 | Viewed by 1625

Abstract

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood [...] Read more.

Interfacial nanobubbles on a superhydrophobic surface can serve as ultrasound cavitation nuclei for continuously promoting sonodynamic therapy, but their poor dispersibility in blood has limited their biomedical application. In this study, we proposed ultrasound-responsive biomimetic superhydrophobic mesoporous silica nanoparticles, modified with red blood cell membrane and loaded with doxorubicin (DOX) (F-MSN-DOX@RBC), for RM-1 tumor sonodynamic therapy. Their mean size and zeta potentials were 232 ± 78.8 nm and −35.57 ± 0.74 mV, respectively. The F-MSN-DOX@RBC accumulation in a tumor was significantly higher than in the control group, and the spleen uptake of F-MSN-DOX@RBC was significantly reduced in comparison to that of the F-MSN-DOX group. Moreover, the cavitation caused by a single dose of F-MSN-DOX@RBC combined with multiple ultrasounds provided continuous sonodynamic therapy. The tumor inhibition rates in the experimental group were 71.5 8 ± 9.54%, which is significantly better than the control group. DHE and CD31 fluorescence staining was used to assess the reactive oxygen species (ROS) generated and the broken tumor vascular system induced by ultrasound. Finally, we can conclude that the combination of anti-vascular therapy, sonodynamic therapy by ROS, and chemotherapy promoted tumor treatment efficacy. The use of red blood cell membrane-modified superhydrophobic silica nanoparticles is a promising strategy in designing ultrasound-responsive nanoparticles to promote drug-release. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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18 pages, 3764 KiB

Open AccessArticle

PVA-Microbubbles as a Radioembolization Platform: Formulation and the In Vitro Proof of Concept

by Valerio Da Ros, Letizia Oddo, Yosra Toumia, Eugenia Guida, Silvia Minosse, Lidia Strigari, Silvia Strolin, Giulia Paolani, Francesca Di Giuliano, Roberto Floris, Francesco Garaci, Susanna Dolci, Gaio Paradossi and Fabio Domenici

Pharmaceutics 2023, 15(1), 217; https://doi.org/10.3390/pharmaceutics15010217 - 08 Jan 2023

Cited by 2 | Viewed by 1755

Abstract

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical [...] Read more.

This proof-of-concept study lays the foundations for the development of a delivery strategy for radioactive lanthanides, such as Yttrium-90, against recurrent glioblastoma. Our appealing hypothesis is that by taking advantage of the combination of biocompatible polyvinyl alcohol (PVA) microbubbles (MBs) and endovascular radiopharmaceutical infusion, a minimally invasive selective radioembolization can be achieved, which can lead to personalized treatments limiting off-target toxicities for the normal brain. The results show the successful formulation strategy that turns the ultrasound contrast PVA-shelled microbubbles into a microdevice, exhibiting good loading efficiency of Yttrium cargo by complexation with a bifunctional chelator. The selective targeting of Yttrium-loaded MBs on the glioblastoma-associated tumor endothelial cells can be unlocked by the biorecognition between the overexpressed α_Vβ₃ integrin and the ligand Cyclo(Arg-Gly-Asp-D-Phe-Lys) at the PVA microbubble surface. Hence, we show the suitability of PVA MBs as selective Y-microdevices for in situ injection via the smallest (i.e., 1.2F) neurointerventional microcatheter available on the market and the accumulation of PVA MBs on the HUVEC cell line model of integrin overexpression, thereby providing ~6 × 10⁻¹⁵ moles of Y90 per HUVEC cell. We further discuss the potential impact of using such versatile PVA MBs as a new therapeutic chance for treating glioblastoma multiforme recurrence. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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11 pages, 2959 KiB

Open AccessArticle

Dual-Modality Molecular Imaging of Tumor via Quantum Dots-Liposome–Microbubble Complexes

by Jieqiong Wang, Yuanyuan Wang, Jie Jia, Chenxing Liu, Dong Ni, Litao Sun and Zhijie Guo

Pharmaceutics 2022, 14(11), 2510; https://doi.org/10.3390/pharmaceutics14112510 - 18 Nov 2022

Cited by 4 | Viewed by 1377

Abstract

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated [...] Read more.

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated αvβ3-integrin-targeted quantum-dots-loaded liposome–microbubble (iRGD-QDLM) complexes that combined ultrasound imaging with optical imaging. The resulting iRGD-QDLM has excellent binding capability to 4T1 breast cancer cells. Ultrasound molecular imaging of 4T1 tumors demonstrated that significantly enhanced ultrasound molecular signals could be observed in comparison with non-targeted QDLM. Importantly, our study also suggested that iRGD-QDL on the surface of microbubbles could be delivered into a tumor by ultrasound-mediated microbubble destruction and adhered to αvβ3 integrin on breast cancer cells, achieving transvascular fluorescent imaging. Our study provides a novel approach to dual-modality molecular imaging of αvβ3 integrin in the tumor tissue. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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13 pages, 2728 KiB

Open AccessArticle

Bimodal Imaging of Tumors via Genetically Engineered Escherichia coli

by Linlin Zhang, Yuanyuan Wang, Dengjin Li, Liang Wang, Zhenzhou Li and Fei Yan

Pharmaceutics 2022, 14(9), 1804; https://doi.org/10.3390/pharmaceutics14091804 - 27 Aug 2022

Cited by 4 | Viewed by 1761 | Correction

Abstract

Although there are emerging innovations of molecular imaging probes to detect and image tumors, most of these molecular dyes and nanoparticles have limitations of low targetability in tumors and fast clearance when administered systemically. In contrast, some bacteria, such as Escherichia coli MG1655 [...] Read more.

Although there are emerging innovations of molecular imaging probes to detect and image tumors, most of these molecular dyes and nanoparticles have limitations of low targetability in tumors and fast clearance when administered systemically. In contrast, some bacteria, such as Escherichia coli MG1655, can selectively proliferate in a hypoxic environment inside of a tumor for several days, which highlights the potential for the development of a genetically encoded multimodal imaging probe to monitor the progress of the tumor. Here, we developed bimodal imaging tumor-homing bacteria (GVs-miRFP680 MG1655) that allow both optical and acoustic imaging in tumor-bearing mice. An in vivo optical image system and a Vevo 2100 imaging system were applied to detect different imaging properties of the engineered bacteria in vivo. Our results show that the GVs-miRFP680 MG1655 bacteria can effectively integrate the advantages of low tissue absorbance from near-infrared fluorescent proteins and non-invasiveness from gas vesicles. We successfully developed GVs-miRFP680 MG1655 bacteria, which have both acoustic and optical imaging abilities in vitro and in vivo. The acoustic signal can last for up to 25 min, while the near-infrared fluorescence signal can last for up to 96 h. The combination of different imaging modalities in the tumor-homing bacteria may contribute to the non-invasive monitoring of the therapeutic effect of bacterial therapy in the future. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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15 pages, 3146 KiB

Open AccessArticle

Ultrasound-Responsive Liposomes for Targeted Drug Delivery Combined with Focused Ultrasound

by Yoon-Seok Kim, Min Jung Ko, Hyungwon Moon, Wonchul Sim, Ae Shin Cho, Gio Gil and Hyun Ryoung Kim

Pharmaceutics 2022, 14(7), 1314; https://doi.org/10.3390/pharmaceutics14071314 - 21 Jun 2022

Cited by 14 | Viewed by 2879

Abstract

Chemotherapeutic drugs are traditionally used for the treatment of cancer. However, chemodrugs generally induce side effects and decrease anticancer effects due to indiscriminate diffusion and poor drug delivery. To overcome these limitations of chemotherapy, in this study, ultrasound-responsive liposomes were fabricated and used [...] Read more.

Chemotherapeutic drugs are traditionally used for the treatment of cancer. However, chemodrugs generally induce side effects and decrease anticancer effects due to indiscriminate diffusion and poor drug delivery. To overcome these limitations of chemotherapy, in this study, ultrasound-responsive liposomes were fabricated and used as drug carriers for delivering the anticancer drug doxorubicin, which was able to induce cancer cell death. The ultrasound-sensitive liposome demonstrated a size distribution of 81.94 nm, and the entrapment efficiency of doxorubicin was 97.1 ± 1.44%. The release of doxorubicin under the ultrasound irradiation was 60% on continuous wave and 50% by optimizing the focused ultrasound conditions. In vivo fluorescence live imaging was used to visualize the doxorubicin release in the MDA-MB-231 xenografted mouse, and it was demonstrated that liposomal drugs were released in response to ultrasound irradiation of the tissue. The combination of ultrasound and liposomes suppressed tumor growth over 56% more than liposomes without ultrasound exposure and 98% more than the control group. In conclusion, this study provides a potential alternative for overcoming the previous limitations of chemotherapeutics. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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15 pages, 2512 KiB

Open AccessArticle

Influence of Acoustic Parameters and Sonication Schemes on Transcranial Blood–Brain Barrier Disruption Induced by Pulsed Weakly Focused Ultrasound

by Yu-Hone Hsu, Wei-Chung Lee, Shing-Shung Chu, Meng-En Chao, Kuo-Sheng Wu, Ren-Shyan Liu and Tai-Tong Wong

Pharmaceutics 2022, 14(6), 1207; https://doi.org/10.3390/pharmaceutics14061207 - 06 Jun 2022

Viewed by 1960

Abstract

Pulsed ultrasound combined with microbubbles use can disrupt the blood–brain barrier (BBB) temporarily; this technique opens a temporal window to deliver large therapeutic molecules into brain tissue. There are published studies to discuss the efficacy and safety of the different ultrasound parameters, microbubble [...] Read more.

Pulsed ultrasound combined with microbubbles use can disrupt the blood–brain barrier (BBB) temporarily; this technique opens a temporal window to deliver large therapeutic molecules into brain tissue. There are published studies to discuss the efficacy and safety of the different ultrasound parameters, microbubble dosages and sizes, and sonication schemes on BBB disruption, but optimal the paradigm is still under investigation. Our study is aimed to investigate how different sonication parameters, time, and microbubble dose can affect BBB disruption, the dynamics of BBB disruption, and the efficacy of different sonication schemes on BBB disruption. Method: We used pulsed weakly focused ultrasound to open the BBB of C57/B6 mice. Evans blue dye (EBD) was used to determine the degree of BBB disruption. With a given acoustic pressure of 0.56 MPa and pulse repetitive frequency of 1 Hz, burst lengths of 10 ms to 50 ms, microbubbles of 100 μL/kg to 300 μL/kg, and sonication times of 60 s to 150 s were used to open the BBB for parameter study. Brain EBD accumulation was measured at 1, 4, and 24 h after sonication for the time–response relationship study; EBD of 100 mg/kg to 200 mg/kg was administered for the dose–response relationship study; EBD injection 0 to 6 h after sonication was performed for the BBB disruption dynamic study; brain EBD accumulation induced by one sonication and two sonications was investigated to study the effectiveness on BBB disruption; and a histology study was performed for brain tissue damage evaluation. Results: Pulsed weakly focused ultrasound opens the BBB extensively. Longer burst lengths and a larger microbubble dose result in a higher degree of BBB disruption; a sonication time longer than 60 s did not increase BBB disruption; brain EBD accumulation peaks 1 h after sonication and remains 81% of the peak level 24 h after sonication; the EBD dose administered correlates with brain EBD accumulation; BBB disruption decreases as time goes on after sonication and lasts for 6 h at least; and brain EBD accumulation induced by two sonication increases 74.8% of that induced by one sonication. There was limited adverse effects associated with sonication, including petechial hemorrhages and mild neuronal degeneration. Conclusions: BBB can be opened extensively and reversibly by pulsed weakly focused ultrasound with limited brain tissue damage. Since EBD combines with albumin in plasma to form a conjugate of 83 kDa, these results may simulate ultrasound-induced brain delivery of therapeutic molecules of this size scale. The result of our study may contribute to finding the optimal paradigm of focused ultrasound-induced BBB disruption. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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12 pages, 6147 KiB

Open AccessArticle

Biosynthetic Gas Vesicles from Halobacteria NRC-1: A Potential Ultrasound Contrast Agent for Tumor Imaging

by Mingjie Wei, Manlin Lai, Jiaqi Zhang, Xiaoqing Pei and Fei Yan

Pharmaceutics 2022, 14(6), 1198; https://doi.org/10.3390/pharmaceutics14061198 - 03 Jun 2022

Cited by 10 | Viewed by 2547

Abstract

Ultrasound contrast agents are valuable for diagnostic imaging and drug delivery. Generally, chemically synthesized microbubbles (MBs) are micro-sized particles. Particle size is a limiting factor for the diagnosis and treatment of many extravascular diseases. Recently, gas vesicles (GVs) from some marine bacteria and [...] Read more.

Ultrasound contrast agents are valuable for diagnostic imaging and drug delivery. Generally, chemically synthesized microbubbles (MBs) are micro-sized particles. Particle size is a limiting factor for the diagnosis and treatment of many extravascular diseases. Recently, gas vesicles (GVs) from some marine bacteria and archaea have been reported as novel nanoscale contrast agents, showing great potential for biomedical applications. However, most of the GVs reported in the literature show poor contrast imaging capabilities due to their small size, especially for the in vivo condition. In this study, we isolated the rugby-ball-shaped GVs from Halobacteria NRC-1 and characterized their contrast imaging properties in vitro and in vivo. Our results showed that GVs could produce stable and strong ultrasound contrast signals in murine liver tumors using clinical diagnostic ultrasound equipment at the optimized parameters. Interestingly, we found these GVs, after systemic administration, were able to perfuse the ischemic region of a tumor where conventional lipid MBs failed, producing a 6.84-fold stronger contrast signal intensity than MBs. Immunohistochemistry staining assays revealed that the nanoscale GVs, in contrast to the microscale MBs, could penetrate through blood vessels. Thus, our study proved these biosynthesized GVs from Halobacterium NRC-1 are useful for future molecular imaging and image-guided drug delivery. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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Review

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22 pages, 2316 KiB

Open AccessReview

Acoustically-Activated Liposomal Nanocarriers to Mitigate the Side Effects of Conventional Chemotherapy with a Focus on Emulsion-Liposomes

by Mah Noor Zafar, Waad H. Abuwatfa and Ghaleb A. Husseini

Pharmaceutics 2023, 15(2), 421; https://doi.org/10.3390/pharmaceutics15020421 - 27 Jan 2023

Cited by 7 | Viewed by 2738

Abstract

To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects [...] Read more.

To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiation, ultrasound (US), pH, or enzymes. This review discusses the acoustic stimulation of different sonosensitive liposomal formulations. Emulsion liposomes, or eLiposomes, are liposomes encapsulating phase-changing nanoemulsion droplets, which promote acoustic droplet vaporization (ADV) upon sonication. This gives eLiposomes the advantage of delivering the encapsulated drug at low intensities and short exposure times relative to liposomes. Other formulations integrating microbubbles and nanobubbles are also discussed. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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28 pages, 19793 KiB

Open AccessReview

Ultrasound and Nanomedicine for Cancer-Targeted Drug Delivery: Screening, Cellular Mechanisms and Therapeutic Opportunities

by Chien-Hsiu Li, Yu-Chan Chang, Michael Hsiao and Ming-Hsien Chan

Pharmaceutics 2022, 14(6), 1282; https://doi.org/10.3390/pharmaceutics14061282 - 16 Jun 2022

Cited by 2 | Viewed by 3440

Abstract

Cancer is a disease characterized by abnormal cell growth. According to a report published by the World Health Organization (WHO), cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018. It should be noted that [...] Read more.

Cancer is a disease characterized by abnormal cell growth. According to a report published by the World Health Organization (WHO), cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018. It should be noted that ultrasound is already widely used as a diagnostic procedure for detecting tumorigenesis. In addition, ultrasound energy can also be utilized effectively for treating cancer. By filling the interior of lipospheres with gas molecules, these particles can serve both as contrast agents for ultrasonic imaging and as delivery systems for drugs such as microbubbles and nanobubbles. Therefore, this review aims to describe the nanoparticle-assisted drug delivery system and how it can enhance image analysis and biomedicine. The formation characteristics of nanoparticles indicate that they will accumulate at the tumor site upon ultrasonic imaging, in accordance with their modification characteristics. As a result of changing the accumulation of materials, it is possible to examine the results by comparing images of other tumor cell lines. It is also possible to investigate ultrasound images for evidence of cellular effects. In combination with a precision ultrasound imaging system, drug-carrying lipospheres can precisely track tumor tissue and deliver drugs to tumor cells to enhance the ability of this nanocomposite to treat cancer. Full article

(This article belongs to the Special Issue Ultrasound-Assisted Drug Delivery System)

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