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1.
Small ; : e2401061, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963320

ABSTRACT

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8 nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1 mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

2.
Biomaterials ; 311: 122646, 2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38852553

ABSTRACT

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

3.
Biomaterials ; 311: 122658, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38901130

ABSTRACT

Bismuth (Bi)-based computed tomography (CT) imaging contrast agents (CAs) hold significant promise for diagnosing gastrointestinal diseases due to their cost-effectiveness, heightened sensitivity, and commendable biocompatibility. Nevertheless, substantial challenges persist in achieving an easy synthesis process, remarkable water solubility, and effective targeting ability for the potential clinical transformation of Bi-based CAs. Herein, we show Bi drug-inspired ultra-small dextran coated bismuth oxide nanoparticles (Bi2O3-Dex NPs) for targeted CT imaging of inflammatory bowel disease (IBD). Bi2O3-Dex NPs are synthesized through a simple alkaline precipitation reaction using bismuth salts and dextran as the template. The Bi2O3-Dex NPs exhibit ultra-small size (3.4 nm), exceptional water solubility (over 200 mg mL-1), high Bi content (19.75 %), excellent biocompatibility and demonstrate higher X-ray attenuation capacity compared to clinical iohexol. Bi2O3-Dex NPs not only enable clear visualization of the GI tract outline and intestinal loop structures in CT imaging but also specifically target and accumulate at the inflammatory site in colitis mice after oral administration, facilitating a precise diagnosis and enabling targeted CT imaging of IBD. Our study introduces a novel and clinically promising strategy for synthesizing high-performance Bi2O3-Dex NPs for diagnosing gastrointestinal diseases.

4.
Adv Healthc Mater ; : e2401653, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830126

ABSTRACT

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

5.
Biomater Sci ; 12(10): 2743-2754, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38639493

ABSTRACT

Highly sensitive iron oxide nanoparticles with stable, safe and efficient surface functionalization, as potential substitutes for gadolinium-based contrast agents (GBCAs) with increasing biosafety concerns, exhibit great potential for high-performance magnetic resonance angiography (MRA). Herein, we developed ultrasmall catechol-PEG-anchored ferrite nanoparticles (PEG-UMFNPs) for highly sensitive MRA. The obtained nanoprobe has a high T1 relaxivity value (7.2 mM-1 s-1) due to its ultrasmall size and Mn doping. It has a suitable hydrodynamic size of 20 nm, which prevents rapid vascular extravasation and renal clearance and prolongs its blood circulation time. In vivo MRA at 3.0 T using the nanoprobe shows that the arteries and veins of rats, even blood vessels as small as 0.32 mm, are distinctly visible, and the contrast enhancement can last for at least 1 h. In addition, due to the outstanding contrast enhancement and long circulation time, the stenosis and recanalization process of the rat's carotid artery can be continuously monitored with a single injection of the nanoprobe. Our study indicates that PEG-UMFNPs are outstanding MR imaging nanoprobes that can be used to diagnose vascular diseases without the biosafety issues of GBCAs.


Subject(s)
Catechols , Contrast Media , Ferric Compounds , Magnetic Resonance Angiography , Polyethylene Glycols , Rats, Sprague-Dawley , Animals , Polyethylene Glycols/chemistry , Rats , Catechols/chemistry , Ferric Compounds/chemistry , Contrast Media/chemistry , Male , Nanoparticles/chemistry , Carotid Arteries/diagnostic imaging
6.
Biomaterials ; 306: 122498, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38310828

ABSTRACT

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.


Subject(s)
Graphite , Hyperthermia, Induced , Neoplasms , Animals , Mice , Neoplasms/therapy , Magnetic Fields
7.
ACS Nano ; 18(6): 4783-4795, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38301134

ABSTRACT

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.


Subject(s)
Acute Kidney Injury , Indoles , Polymers , Humans , Contrast Media/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnostic imaging , Magnetic Resonance Imaging/methods
8.
Colloids Surf B Biointerfaces ; 236: 113796, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38368756

ABSTRACT

Kidney disease is currently prevalent worldwide but only shows insidious symptoms in the early stages. The second near-infrared window (NIR-II) fluorescence imaging has become a widely used preclinical technology for evaluating renal dysfunction due to its high resolution and sensitivity. However, bright renal clearable NIR-II fluorescence nanoprobes with a simple synthesis process are still lacking. Herein, we develop a lactoglobulin (LG)@dye nanoprobe for NIR-II fluorescence imaging of kidney dysfunction in vivo based on a purification-free method. The nanoprobe was synthesized by simply mixing LG and IR820 in aqueous solutions at 70 °C for 2 h based on the covalent interaction between the meso-Cl in IR820 and LG. The synthesized LG@IR820 nanoprobe has bright and stable NIR-II fluorescence, ultra-small size (<5 nm), low toxicity, and renal-clearable ability. The high reaction efficiency and pure aqueous reaction media make the synthesis method purification-free. In a unilateral ureteral obstruction mouse model, incipient renal dysfunction assessment was achieved by LG@IR820 nanoprobe, which couldn't be diagnosed with conventional kidney function indicators. This study provides a bright and purification-free NIR-II LG@IR820 nanoprobe to visualize kidney dysfunction at the early stage.


Subject(s)
Kidney Diseases , Lactoglobulins , Animals , Mice , Kidney/diagnostic imaging , Kidney Diseases/diagnostic imaging , Water , Optical Imaging/methods , Fluorescent Dyes
9.
Anal Chem ; 96(8): 3318-3328, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38355404

ABSTRACT

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM-1 s-1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.


Subject(s)
Manganese , Renal Insufficiency , Humans , Rats , Animals , Manganese/chemistry , Gadolinium DTPA/chemistry , Magnetic Resonance Imaging/methods , Contrast Media/chemistry , Kidney/diagnostic imaging
10.
ACS Appl Mater Interfaces ; 16(5): 5474-5485, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38271189

ABSTRACT

Contrast-enhanced magnetic resonance imaging (MRI) is seriously limited in kidney injury detection due to the nephrotoxicity of clinically used gadolinium-based contrast agents. Herein, we propose a noninvasive method for the assessment of kidney injury by combining structure and function information based on manganese (Mn)-enhanced MRI for the first time. As a proof of concept, the Mn-melanin nanoprobe with good biocompatibility and excellent T1 relaxivity is applied in MRI of a unilateral ureteral obstruction mice model. The abundant renal structure and function information is obtained through qualitative and quantitative analysis of MR images, and a brand new comprehensive assessment framework is proposed to precisely identify the degree of kidney injury successfully. Our study demonstrates that Mn-enhanced MRI is a promising approach for the highly sensitive and biosafe assessment of kidney injury in vivo.


Subject(s)
Artificial Intelligence , Manganese , Mice , Animals , Manganese/chemistry , Magnetic Resonance Imaging/methods , Kidney/diagnostic imaging , Contrast Media/chemistry
11.
Adv Healthc Mater ; 13(9): e2303389, 2024 04.
Article in English | MEDLINE | ID: mdl-38164886

ABSTRACT

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15 mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.


Subject(s)
Contrast Media , Magnetic Resonance Angiography , Contrast Media/pharmacology , Magnetic Resonance Imaging/methods , Gadolinium/pharmacology
12.
Adv Healthc Mater ; 13(12): e2304577, 2024 05.
Article in English | MEDLINE | ID: mdl-38278515

ABSTRACT

Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.


Subject(s)
Ferric Compounds , Kidney , Magnetic Resonance Imaging , Rats, Sprague-Dawley , Animals , Magnetic Resonance Imaging/methods , Ferric Compounds/chemistry , Rats , Kidney/diagnostic imaging , Kidney/pathology , Contrast Media/chemistry , Male , Early Diagnosis , Kidney Diseases/diagnostic imaging
13.
Adv Sci (Weinh) ; 11(11): e2307823, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38164827

ABSTRACT

The magnetic hyperthermia-based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)-drug implant is established in an ultra-facile and universal way for ultralow-power MHCT of tumors in vivo for the first time. The IF-drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra-high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via "capillary action". In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large-scale preparation of IF-drug implants for biological application. As a proof of concept, IF-doxorubicin (IF-DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF-drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow-power combination therapy.


Subject(s)
Hyperthermia, Induced , Neoplasms , Humans , Drug Implants , Iron , Neoplasms/drug therapy , Doxorubicin , Hyperthermia, Induced/methods , Magnetic Fields
14.
Biomaterials ; 305: 122422, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38128318

ABSTRACT

Computed tomography angiography (CTA) is one of the most important diagnosis techniques for various vascular diseases in clinic. However, metallic artifacts caused by metal implants and calcified plaques in more and more patients severely hinder its wide applications. Herein, we propose an improved metallic artifacts-free spectral CTA technique based on renal clearable bismuth chelate (Bi-DTPA dimeglumine) for the first time. Bi-DTPA dimeglumine owns the merits of ultra-simple synthetic process, approximately 100% of yield, large-scale production capability, good biocompatibility, and favorable renal clearable ability. More importantly, Bi-DTPA dimeglumine shows superior contrast-enhanced effect in CTA compared with clinical iohexol at a wide range of X-ray energies especially in higher X-ray energy. In rabbits' model with metallic transplants, Bi-DTPA dimeglumine assisted-spectral CTA can not only effectively mitigate metallic artifacts by reducing beam hardening effect under high X-ray energy, but also enables accurate delineation of vascular structure. Our proposed strategy opens a revolutionary way to solve the bottleneck problem of metallic artifacts in CTA examinations.


Subject(s)
Bismuth , Computed Tomography Angiography , Animals , Humans , Rabbits , Computed Tomography Angiography/methods , Artifacts , Tomography, X-Ray Computed/methods , Pentetic Acid
15.
Adv Healthc Mater ; 13(9): e2303268, 2024 04.
Article in English | MEDLINE | ID: mdl-38140916

ABSTRACT

The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn2+ component allows real-time dynamic visualization of the ALG-Mn hydrogel at the tumor site via magnetic resonance imaging. To the best of knowledge, the proposed ALG-Mn hydrogel represents the minimalist biocompatible platform for imaging-guided synergistic MWA and CDT toward achieving complete tumor clearance.


Subject(s)
Manganese , Neoplasms , Humans , Microwaves/therapeutic use , Hydrogels , Neoplasm, Residual/drug therapy , Neoplasms/drug therapy , Magnetic Resonance Imaging , Tumor Microenvironment , Cell Line, Tumor
16.
ACS Appl Bio Mater ; 6(11): 4906-4913, 2023 11 20.
Article in English | MEDLINE | ID: mdl-37917917

ABSTRACT

Contrast-enhanced magnetic resonance angiography is a powerful and effective method to accurately diagnose carotid artery stenosis. Small molecular gadolinium (Gd)-based agents have reliable signal enhancement, but their short circulating time may result in a loss of image resolution due to insufficient vascular filling or contrast agent emptying. Here, we report an MRA imaging approach to diagnose carotid artery stenosis using long-circulating bovine serum albumin (BSA)-Gd2O3 nanoparticles (NPs). The BSA-Gd2O3 NPs synthesized by a simple biomineralization approach exhibit admirable monodispersity, uniform size, favorable aqueous solubility, good biocompatibility, and high relaxivity (14.86 mM-1 s-1 in water, 6.41 mM-1 s-1 in plasma). In vivo MRA imaging shows that outstanding vascular enhancement of BSA-Gd2O3 NPs (0.05 mmol Gd/kg, half the dose in the clinic) can be maintained for at least 2 h, much longer than Gd-DTPA. Vessels as small as 0.3 mm can be clearly observed in MRA images with high resolution. In a rat carotid artery stenosis model, the BSA-Gd2O3 NPs-based MRA enables the precise diagnosis of the severity and location and the therapeutic effect following the surgery of carotid artery stenosis, which provides a method for the theranostics of vascular diseases.


Subject(s)
Carotid Stenosis , Nanoparticles , Rats , Animals , Magnetic Resonance Angiography/methods , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Contrast Media , Gadolinium , Serum Albumin, Bovine
17.
ACS Nano ; 17(22): 22399-22409, 2023 11 28.
Article in English | MEDLINE | ID: mdl-37930191

ABSTRACT

Precise delivery of radionuclides and anticancer drugs to tumor tissue is crucial to ensuring drug synergism and optimal therapeutic effects in radionuclide-based combination radio-chemotherapy. However, current codelivery vectors often rely on physical embedment/adsorption to load anticancer drugs, which lacks precise mechanisms for drug loading and release, resulting in unpredictable combination effects. Herein, a macrocyclic-albumin conjugate (MAC) that enables precise loading and controlled release of anticancer drugs is presented. By conjugating multiple macrocyclic hosts (sulfonate azocalix[4]arenes, SAC4A) to albumin molecules, the MAC facilitates the precise loading of anticancer drugs through host-guest interactions and site-specific labeling of radionuclides. Furthermore, the MAC degrades under hypoxic conditions, enabling the release of loaded drugs upon reaching tumor tissues. Through precise loading and targeted delivery of radionuclides and anticancer drugs, MAC achieves efficient cancer diagnosis and combined radio-chemotherapy in breast cancer cell (4T1)-bearing mice. Considering that SAC4A can load many anticancer drugs, MAC may provide a promising platform for effective combination radio-chemotherapy.


Subject(s)
Antineoplastic Agents , Nanoparticles , Neoplasms , Animals , Mice , Drug Delivery Systems , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Neoplasms/drug therapy , Albumins , Drug Synergism
18.
Biomaterials ; 302: 122328, 2023 11.
Article in English | MEDLINE | ID: mdl-37722184

ABSTRACT

CRISPR-based base editors (BEs) are powerful tools for precise nucleotide substitution in a wide range of organisms, but spatiotemporal control of base editing remains a daunting challenge. Herein, we develop a photoactivatable base editor (Mag-ABE) for spatiotemporally controlled genome editing in vivo for the first time. The base editing activity of Mag-ABE can be activated by blue light for spatiotemporal regulation of both EGFP reporter gene and various endogenous genes editing. Meanwhile, the Mag-ABE prefers to edit A4 and A5 positions rather than to edit A6 position, showing the potential to decrease bystander editing of traditional adenine base editors. After integration with upconversion nanoparticles as a light transducer, the Mag-ABE is further applied for near-infrared (NIR) light-activated base editing of liver in transgenic reporter mice successfully. This study opens a promising way to improve the operability, safety, and precision of base editing.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Mice , Animals , CRISPR-Cas Systems/genetics , Genome , Adenine , Light
19.
Theranostics ; 13(14): 4781-4801, 2023.
Article in English | MEDLINE | ID: mdl-37771786

ABSTRACT

Hitchhiking, a recently developed bio-inspired cargo delivery system, has been harnessed for diverse applications. By leveraging the interactions between nanoparticles and circulatory cells or proteins, hitchhiking enables efficient navigation through the vasculature while evading immune system clearance. Moreover, it allows for targeted delivery of nutrients to tissues, surveillance of the immune system, and pathogen elimination. Various synthetic nanomaterials have been developed to facilitate hitchhiking with circulatory cells or proteins. By combining the advantages of synthetic nanomaterials and circulatory cells or proteins, hitchhiking nanomaterials demonstrate several advantages over conventional vectors, including enhanced circulatory stability and optimized therapeutic efficacy. This review provides an overview of general strategies for hitchhiking, choices of cells and proteins, and recent advances of hitchhiking nanomaterials for biomedical applications.

20.
Biomater Sci ; 11(12): 4289-4297, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37063063

ABSTRACT

As Gd-based contrast agents suffer from the risk of causing nephrogenic systemic fibrosis, less toxic contrast agents are urgently needed in contrast-enhanced magnetic resonance imaging (CE-MRI) of kidney injury. Herein, we develop a non-invasive diagnosis method for acute kidney injury using CE-MRI based on manganese-doped carbon dots (Mn-CDs). The synthesized Mn-CDs possess an ultrasmall size of 5 nm, good biocompatibility, and a high T1 relaxation rate (10.8 mM-1 s-1), which can produce effective positive enhancement in the kidneys and clearly show the fine structures of the kidneys including the cortex, outer medulla, and inner medulla. In an acute kidney injury model, Mn-CDs-based CE-MRI can not only accurately and intuitively reveal the site of kidney injury consistent with the pathological analysis, but also reflect the functional changes in the injured kidney. Collectively, our study provides a new strategy for the non-invasive diagnosis of acute kidney injury using CE-MRI based on Mn-CDs.


Subject(s)
Acute Kidney Injury , Contrast Media , Humans , Contrast Media/chemistry , Carbon , Magnetic Resonance Imaging/methods , Manganese/chemistry , Acute Kidney Injury/chemically induced , Acute Kidney Injury/diagnostic imaging
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