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1.
J Nanobiotechnology ; 22(1): 235, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38725031

ABSTRACT

Different from most of the conventional platforms with dissatisfactory theranostic capabilities, supramolecular nanotheranostic systems have unparalleled advantages via the artful combination of supramolecular chemistry and nanotechnology. Benefiting from the tunable stimuli-responsiveness and compatible hierarchical organization, host-guest interactions have developed into the most popular mainstay for constructing supramolecular nanoplatforms. Characterized by the strong and diverse complexation property, cucurbit[8]uril (CB[8]) shows great potential as important building blocks for supramolecular theranostic systems. In this review, we summarize the recent progress of CB[8]-based supramolecular theranostics regarding the design, manufacture and theranostic mechanism. Meanwhile, the current limitations and corresponding reasonable solutions as well as the potential future development are also discussed.


Subject(s)
Bridged-Ring Compounds , Imidazoles , Theranostic Nanomedicine , Theranostic Nanomedicine/methods , Bridged-Ring Compounds/chemistry , Imidazoles/chemistry , Humans , Animals , Nanoparticles/chemistry , Heterocyclic Compounds, 2-Ring , Macrocyclic Compounds , Imidazolidines
2.
Sci Rep ; 14(1): 10646, 2024 05 09.
Article in English | MEDLINE | ID: mdl-38724530

ABSTRACT

Individual theranostic agents with dual-mode MRI responses and therapeutic efficacy have attracted extensive interest due to the real-time monitor and high effective treatment, which endow the providential treatment and avoid the repeated medication with side effects. However, it is difficult to achieve the integrated strategy of MRI and therapeutic drug due to complicated synthesis route, low efficiency and potential biosafety issues. In this study, novel self-assembled ultrasmall Fe3O4 nanoclusters were developed for tumor-targeted dual-mode T1/T2-weighted magnetic resonance imaging (MRI) guided synergetic chemodynamic therapy (CDT) and chemotherapy. The self-assembled ultrasmall Fe3O4 nanoclusters synthesized by facilely modifying ultrasmall Fe3O4 nanoparticles with 2,3-dimercaptosuccinic acid (DMSA) molecule possess long-term stability and mass production ability. The proposed ultrasmall Fe3O4 nanoclusters shows excellent dual-mode T1 and T2 MRI capacities as well as favorable CDT ability due to the appropriate size effect and the abundant Fe ion on the surface of ultrasmall Fe3O4 nanoclusters. After conjugation with the tumor targeting ligand Arg-Gly-Asp (RGD) and chemotherapy drug doxorubicin (Dox), the functionalized Fe3O4 nanoclusters achieve enhanced tumor accumulation and retention effects and synergetic CDT and chemotherapy function, which serve as a powerful integrated theranostic platform for cancer treatment.


Subject(s)
Magnetic Resonance Imaging , Theranostic Nanomedicine , Magnetic Resonance Imaging/methods , Theranostic Nanomedicine/methods , Animals , Mice , Humans , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Cell Line, Tumor , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/therapy , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Succimer/chemistry , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology
3.
J Inorg Biochem ; 256: 112569, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38701687

ABSTRACT

The clinical success of [223Ra]RaCl2 (Xofigo®) for the palliative treatment of bone metastases in patients with prostate cancer has highlighted the therapeutic potential of α-particle emission. Expanding the applicability of radium-223 in Targeted Alpha Therapy of non-osseous tumors is followed up with significant interest, as it holds the potential to unveil novel treatment options in the comprehensive management of cancer. Moreover, the use of barium radionuclides, like barium-131 and -135m, is still unfamiliar in nuclear medicine applications, although they can be considered as radium-223 surrogates for imaging purposes. Enabling these applications requires the establishment of chelators able to form stable complexes with radium and barium radionuclides. Until now, only a limited number of ligands have been suggested and these molecules have been primarily inspired by existing structures known for their ability to complex large metal cations. However, a systematic inspection of chelators specifically tailored to Ra2+ and Ba2+ has yet to be conducted. This work delves into a comprehensive investigation of a series of small organic ligands, aiming to unveil the coordination preferences of both radium-223 and barium-131/135m. Electronic binding energies of both metal cations to each ligand were theoretically computed via Density Functional Theory calculations (COSMO-ZORA-PBE-D3/TZ2P), while thermodynamic stability constants were experimentally determined for Ba2+-ligand complexes by potentiometry, NMR and UV-Vis spectroscopies. The outcomes revealed malonate, 2-hydroxypyridine 1-oxide and picolinate as the most favorable building blocks to design multidentate chelators. These findings serve as foundation guidelines, propelling the development of cutting-edge radium-223- and barium-131/135m-based radiopharmaceuticals for Targeted Alpha Therapy and theranostics of cancer.


Subject(s)
Radium , Radium/chemistry , Radium/therapeutic use , Humans , Radioisotopes/chemistry , Coordination Complexes/chemistry , Coordination Complexes/therapeutic use , Barium/chemistry , Alpha Particles/therapeutic use , Chelating Agents/chemistry , Chelating Agents/therapeutic use , Neoplasms/drug therapy , Theranostic Nanomedicine/methods , Metals, Alkaline Earth/chemistry , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/therapeutic use
5.
Int J Mol Sci ; 25(9)2024 May 02.
Article in English | MEDLINE | ID: mdl-38732200

ABSTRACT

We are living in an era of advanced nanoscience and nanotechnology. Numerous nanomaterials, culminating in nanorobots, have demonstrated ingenious applications in biomedicine, including breast cancer (BC) nano-theranostics. To solve the complicated problem of BC heterogeneity, non-targeted drug distribution, invasive diagnostics or surgery, resistance to classic onco-therapies and real-time monitoring of tumors, nanorobots are designed to perform multiple tasks at a small scale, even at the organelles or molecular level. Over the last few years, most nanorobots have been bioengineered as biomimetic and biocompatible nano(bio)structures, resembling different organisms and cells, such as urchin, spider, octopus, fish, spermatozoon, flagellar bacterium or helicoidal cyanobacterium. In this review, readers will be able to deepen their knowledge of the structure, behavior and role of several types of nanorobots, among other nanomaterials, in BC theranostics. We summarized here the characteristics of many functionalized nanodevices designed to counteract the main neoplastic hallmark features of BC, from sustaining proliferation and evading anti-growth signaling and resisting programmed cell death to inducing angiogenesis, activating invasion and metastasis, preventing genomic instability, avoiding immune destruction and deregulating autophagy. Most of these nanorobots function as targeted and self-propelled smart nano-carriers or nano-drug delivery systems (nano-DDSs), enhancing the efficiency and safety of chemo-, radio- or photodynamic therapy, or the current imagistic techniques used in BC diagnosis. Most of these nanorobots have been tested in vitro, using various BC cell lines, as well as in vivo, mainly based on mice models. We are still waiting for nanorobots that are low-cost, as well as for a wider transition of these favorable effects from laboratory to clinical practice.


Subject(s)
Breast Neoplasms , Nanotechnology , Humans , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Breast Neoplasms/diagnosis , Female , Nanotechnology/methods , Animals , Nanostructures/chemistry , Nanostructures/therapeutic use , Robotics/methods , Theranostic Nanomedicine/methods , Drug Delivery Systems/methods , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology
6.
Anal Chem ; 96(19): 7687-7696, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38693877

ABSTRACT

Smart theranostic nanoprobes with the integration of multiple therapeutic modalities are preferred for precise diagnosis and efficient therapy of tumors. However, it remains a big challenge to arrange the imaging and two or more kinds of therapeutic agents without weakening the intended performances. In addition, most existing fluorescence (FL) imaging agents suffer from low spatiotemporal resolution due to the short emission wavelength (<900 nm). Here, novel three-in-one Ag2S quantum dot (QD)-based smart theranostic nanoprobes were proposed for in situ ratiometric NIR-II FL imaging-guided ion/gas combination therapy of tumors. Under the acidic tumor microenvironment, three-in-one Ag2S QDs underwent destructive degradation, generating toxic Ag+ and H2S. Meanwhile, their FL emission at 1270 nm was weakened. Upon introduction of a downconversion nanoparticle (DCNP) as the delivery carrier and NIR-II FL reference signal unit, the formed Ag2S QD-based theranostic nanoprobes could achieve precise diagnosis of tumors through ratiometric NIR-II FL signals. Also, the generated Ag+ and H2S enabled specific ion/gas combination therapy toward tumors. By combining the imaging and therapeutic functions, three-in-one Ag2S QDs may open a simple yet reliable avenue to design theranostic nanoprobes.


Subject(s)
Optical Imaging , Quantum Dots , Silver Compounds , Quantum Dots/chemistry , Silver Compounds/chemistry , Humans , Animals , Mice , Infrared Rays , Theranostic Nanomedicine , Hydrogen Sulfide/analysis , Hydrogen Sulfide/chemistry , Hydrogen-Ion Concentration
7.
Theranostics ; 14(6): 2490-2525, 2024.
Article in English | MEDLINE | ID: mdl-38646646

ABSTRACT

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases. Accurate detection and timely therapeutic intervention on inflammatory dysregulation are crucial for the effective therapy of inflammation-associated diseases. However, the clinical outcomes of inflammation-involved disorders are still unsatisfactory. Therefore, there is an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations with traditional therapeutics. Biomedical nanotechnology is one of the promising fields that can potentially transform the diagnosis and treatment of inflammation. In this review, we outline recent advances in biomedical nanotechnology for the diagnosis and treatment of inflammation, with special attention paid to nanosensors and nanoprobes for precise diagnosis of inflammation-related diseases, emerging anti-inflammatory nanotherapeutics, as well as nanotheranostics and combined anti-inflammatory applications. Moreover, the prospects and challenges for clinical translation of nanoprobes and anti-inflammatory nanomedicines are highlighted.


Subject(s)
Inflammation , Nanotechnology , Theranostic Nanomedicine , Humans , Inflammation/diagnosis , Theranostic Nanomedicine/methods , Nanotechnology/methods , Animals , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Nanomedicine/methods , Nanoparticles
8.
J Colloid Interface Sci ; 668: 88-97, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38669999

ABSTRACT

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.


Subject(s)
Doxorubicin , Hydrogen Peroxide , Oxygen , Photochemotherapy , Theranostic Nanomedicine , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/metabolism , Animals , Mice , Doxorubicin/pharmacology , Doxorubicin/chemistry , Doxorubicin/administration & dosage , Oxygen/chemistry , Oxygen/metabolism , Humans , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Particle Size , Surface Properties , Drug Screening Assays, Antitumor , Cell Survival/drug effects , Cell Proliferation/drug effects , Cell Line, Tumor , Peroxides/chemistry , Peroxides/pharmacology , Nanoparticles/chemistry , Mice, Inbred BALB C , Zinc/chemistry , Zinc/pharmacology , Tumor Microenvironment/drug effects , Antibiotics, Antineoplastic/pharmacology , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/administration & dosage
9.
ACS Nano ; 18(18): 11560-11572, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38682810

ABSTRACT

Second near-infrared (NIR-II) carbon dots, with absorption or emission between 1000 and 1700 nm, are gaining increasing attention in the biomaterial field due to their distinctive properties, which include straightforward preparation processes, stable photophysical characteristics, excellent biocompatibility, and low cost. As a result, there is a growing focus on the controlled synthesis and modulation of the photochemical and photophysical properties of NIR-II carbon dots, with the aim to further expand their biomedical applications, a current research hotspot. This account aims to provide a comprehensive overview of the recent advancements in NIR-II carbon dots within the biomedical field. The review will cover the following topics: (i) the design, synthesis, and purification of NIR-II carbon dots, (ii) the surface modification strategies, and (iii) the biomedical applications, particularly in the domain of cancer theranostics. Additionally, this account addresses the challenges encountered by NIR-II carbon dots and will outline future directions in the realm of cancer theranostics. By exploring carbon-based NIR-II biomaterials, we can anticipate that this contribution will garner increased attention and contribute to the development of next-generation advanced functional carbon dots, thereby offering enhanced tools and strategies in the biomedical field.


Subject(s)
Carbon , Infrared Rays , Quantum Dots , Carbon/chemistry , Quantum Dots/chemistry , Humans , Neoplasms/drug therapy , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Animals , Theranostic Nanomedicine
10.
J Am Chem Soc ; 146(18): 12836-12849, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38683943

ABSTRACT

The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the Galleria melonella animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.


Subject(s)
Antineoplastic Agents , Cations , Phenazines , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cations/chemistry , Cations/pharmacology , Phenazines/chemistry , Phenazines/pharmacology , Lysosomes/metabolism , Lysosomes/drug effects , HEK293 Cells , Apoptosis/drug effects , Drug Screening Assays, Antitumor , Cell Line, Tumor , Animals , Theranostic Nanomedicine , Molecular Structure
11.
Colloids Surf B Biointerfaces ; 238: 113907, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608464

ABSTRACT

Multifunctional agents with therapeutic and diagnostic capabilities are imperative to the prevention of Alzheimer's disease (AD), which is considered due to abnormal aggregation and deposition of ß-amyloid protein (Aß) as well as oxidative stress. Herein, quercetin (Que)- and p-phenylenediamine (p-PD)-derived red emission carbon dots (CDs) synthesized via a one-step hydrothermal method were designed as a novel theranostic nano-agent for the multi-target treatment of AD. R-CD-75 with an optimized composition exhibited significant inhibition of Aß aggregation and rapid depolymerization of mature Aß fibrils (<4 h) at micromolar concentrations (2 and 5 µg/mL, respectively). Moreover, R-CD-75 potently scavenged reactive oxygen species and showed turned-on red fluorescence imaging of Aß plaques both in vitro and in vivo. In vitro assays proved that R-CD-75 significantly mitigated the Aß-induced cytotoxicity and enhanced the cultured cell viability from 74.9 % to 98.0 %, while in vivo studies demonstrated that R-CD-75 prolonged the lifespan of AD nematodes by over 50 % (from 13 to 20 d). Compared to the precursors Que and p-PD, R-CD-75 inherited some of their structures and functional groups, such as aromatic structures, phenolic hydroxyl and amino groups, which were considered to interact with Aß species through hydrogen bonding, electrostatic interactions, hydrophobic interactions, and π-π stacking, thus contributing to its effectiveness in its theranostic functions. This research has opened a new avenue to the development of potent theranostic agents by designing novel carbon dots.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Carbon , Quantum Dots , Quercetin , Theranostic Nanomedicine , Quercetin/chemistry , Quercetin/pharmacology , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/chemistry , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Alzheimer Disease/metabolism , Carbon/chemistry , Carbon/pharmacology , Quantum Dots/chemistry , Animals , Humans , Cell Survival/drug effects , Reactive Oxygen Species/metabolism , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/metabolism , Particle Size
12.
ACS Appl Mater Interfaces ; 16(17): 21557-21570, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38648555

ABSTRACT

We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.


Subject(s)
Micelles , Positron-Emission Tomography , Radiation-Sensitizing Agents , Theranostic Nanomedicine , Animals , Humans , Radiation-Sensitizing Agents/chemistry , Radiation-Sensitizing Agents/pharmacology , Radiation-Sensitizing Agents/chemical synthesis , Mice , Cell Line, Tumor , Fluorocarbons/chemistry , Fluorocarbons/pharmacology , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Neoplasms/pathology
13.
J Mater Chem B ; 12(17): 4248-4261, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38602387

ABSTRACT

Prolonged use of very commonly prescribed non-steroidal anti-inflammatory drugs (NSAIDs) is often associated with undesired side effects, including gastrointestinal ulcers due to the non-selective inhibition of cyclooxygenases. We describe the development of an inflammatory-stimuli-responsive turn-on fluorogenic theranostic prodrug DCF-HS for adjuvant drug delivery. Upon activation by reactive oxygen species (ROS), the prodrug releases diclofenac DCF (active drug) and the NIR fluorophore DCI-NH2 along with carbonyl sulfide (COS). The second activation of COS by the enzyme carbonic anhydrase (CA) generates hydrogen sulfide (H2S). The prodrug was conveniently synthesized using multi-step organic synthesis. The UV-Vis and fluorescence studies revealed the selective reactivity of DCF-HS towards ROS such as H2O2 in the aqueous phase and the desired uncaging of the drug DCF with turn-on NIR fluorescent reporter under physiological conditions. Furthermore, the release of fluorophore DCI-NH2 and drug DCF was confirmed using the reverse phase HPLC method. Compatibility of prodrug activation was studied next in the cellular medium. The prodrug DCF-HS was non-toxic in a representative cancer cell line (HeLa) and a macrophage cell line (RAW 264.7) up to 100 µM concentration, indicating its biocompatibility. The intracellular ROS-mediated activation of the prodrug with the release of NIR dye DCI-NH2 and H2S was investigated in HeLa cells using the H2S-selective probe WSP2. The anti-inflammatory activity of the active drug DCF from the prodrug DCF-HS was studied in the lipopolysaccharide (LPS)-induced macrophage cell line and compared to that of the parent drug DCF using western blot analysis and it was found that the active drug resulted in pronounced inhibition of COX-2 in a dose-dependent manner. Finally, the anti-inflammatory potential of the prodrug and the turn-on fluorescence were validated in the inflammation-induced Wister rat models.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Diclofenac , Hydrogen Sulfide , Prodrugs , Prodrugs/pharmacology , Prodrugs/chemistry , Prodrugs/chemical synthesis , Hydrogen Sulfide/metabolism , Animals , Humans , Diclofenac/pharmacology , HeLa Cells , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Rats , Theranostic Nanomedicine , Inflammation/drug therapy , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacology , Fluorescent Dyes/chemical synthesis , Mice , RAW 264.7 Cells , Drug Delivery Systems , Edema/drug therapy , Edema/chemically induced
14.
ACS Nano ; 18(18): 11837-11848, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38654614

ABSTRACT

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.


Subject(s)
Biofilms , Lanthanoid Series Elements , Pseudomonas aeruginosa , Theranostic Nanomedicine , Biofilms/drug effects , Animals , Mice , Pseudomonas aeruginosa/drug effects , Lanthanoid Series Elements/chemistry , Lanthanoid Series Elements/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Humans , Photothermal Therapy , Mice, Inbred BALB C
15.
Biomater Sci ; 12(10): 2614-2625, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38591255

ABSTRACT

Chlorambucil (Cbl) is a DNA alkylating drug in the nitrogen mustard family, but the clinical applications of nitrogen mustard antitumor drugs are frequently limited by their poor aqueous solubility, poor cellular uptake, lack of targeting, and severe side effects. Additionally, mitochondria are the energy factories for cells, and tumor cells are more susceptible to mitochondrial dysfunction than some healthy cells, thus making mitochondria an important target for tumor therapy. As a proof-of-concept, direct delivery of Cbl to tumor cells' mitochondria will probably bring about new opportunities for the nitrogen mustard family. Furthermore, IR775 chloride is a small-molecule lipophilic cationic heptamethine cyanine dye with potential advantages of mitochondria targeting, near-infrared (NIR) fluorescence imaging, and preferential internalization towards tumor cells. Here, an amphiphilic drug conjugate was facilely prepared by covalently coupling chlorambucil with IR775 chloride and further self-assembly to form a carrier-free self-delivery theranostic system, in which the two components are both functional units aimed at theranostic improvement. The theranostic IR775-Cbl potentiated typical "1 + 1 > 2" tumor inhibition through specific accumulation in mitochondria, which triggered a remarkable decrease in mitochondrial membrane potential and ATP generation. In vivo biodistribution and kinetic monitoring were achieved by real-time NIR fluorescence imaging to observe its transport inside a living body. Current facile mitochondria-targeting modification with clinically applied drugs was promising for endowing traditional drugs with targeting, imaging, and improved potency in disease theranostics.


Subject(s)
Carbocyanines , Chlorambucil , Mitochondria , Nanoparticles , Chlorambucil/chemistry , Chlorambucil/pharmacology , Chlorambucil/administration & dosage , Mitochondria/drug effects , Mitochondria/metabolism , Animals , Humans , Nanoparticles/chemistry , Carbocyanines/chemistry , Mice , Polymers/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Mice, Nude , Cell Line, Tumor , Mice, Inbred BALB C , Theranostic Nanomedicine , Indoles/chemistry , Indoles/pharmacology , Indoles/administration & dosage , Female
16.
Biomater Sci ; 12(10): 2705-2716, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38607326

ABSTRACT

Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.


Subject(s)
Glioma , Macrophages , Theranostic Nanomedicine , Glioma/diagnostic imaging , Glioma/drug therapy , Glioma/metabolism , Glioma/pathology , Animals , Mice , Macrophages/metabolism , Macrophages/drug effects , Magnetic Iron Oxide Nanoparticles/chemistry , Magnetic Resonance Imaging , Humans , Cell Line, Tumor , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Reactive Oxygen Species/metabolism , Cell Membrane/metabolism , Tumor Microenvironment/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects
17.
ACS Biomater Sci Eng ; 10(5): 2703-2724, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38644798

ABSTRACT

The scientific world is increasingly focusing on rare earth metal oxide nanomaterials due to their consequential biological prospects, navigated by breakthroughs in biomedical applications. Terbium belongs to rare earth elements (lanthanide series) and possesses remarkably strong luminescence at lower energy emission and signal transduction properties, ushering in wide applications for diagnostic measurements (i.e., bioimaging, biosensors, fluorescence imaging, etc.) in the biomedical sectors. In addition, the theranostic applications of terbium-based nanoparticles further permit the targeted delivery of drugs to the specific site of the disease. Furthermore, the antimicrobial properties of terbium nanoparticles induced via reactive oxygen species (ROS) cause oxidative damage to the cell membrane and nuclei of living organisms, ion release, and surface charge interaction, thus further creating or exhibiting excellent antioxidant characteristics. Moreover, the recent applications of terbium nanoparticles in tissue engineering, wound healing, anticancer activity, etc., due to angiogenesis, cell proliferation, promotion of growth factors, biocompatibility, cytotoxicity mitigation, and anti-inflammatory potentials, make this nanoparticle anticipate a future epoch of nanomaterials. Terbium nanoparticles stand as a game changer in the realm of biomedical research, proffering a wide array of possibilities, from revolutionary imaging techniques to advanced drug delivery systems. Their unique properties, including luminescence, magnetic characteristics, and biocompatibility, have redefined the boundaries of what can be achieved in biomedicine. This review primarily delves into various mechanisms involved in biomedical applications via terbium-based nanoparticles due to their physicochemical characteristics. This review article further explains the potential biomedical applications of terbium nanoparticles with in-depth significant mechanisms from the individual literature. This review additionally stands as the first instance to furnish a "single-platted" comprehensive acquaintance of terbium nanoparticles in shaping the future of healthcare as well as potential limitations and overcoming strategies that require exploration before being trialed in clinical settings.


Subject(s)
Terbium , Humans , Terbium/chemistry , Animals , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/chemistry , Tissue Engineering/methods , Theranostic Nanomedicine/methods , Drug Delivery Systems/methods
18.
Chem Commun (Camb) ; 60(40): 5322-5325, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38666540

ABSTRACT

A small molecule-based NIR-II type-I photosensitizer (IT-IC) with a strong push-pull effect and good planar π-conjugated structure was synthesized. The IT-IC NPs exhibited strong light absorption, outstanding NIR-II fluorescence emission, excellent photothermal conversion and efficient type-I/II ROS generation, showing encouraging therapeutic outcomes for hypoxic tumors.


Subject(s)
Infrared Rays , Photosensitizing Agents , Theranostic Nanomedicine , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Humans , Animals , Mice , Cell Line, Tumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Reactive Oxygen Species/metabolism , Neoplasms/drug therapy , Neoplasms/pathology , Molecular Structure , Photochemotherapy , Tumor Hypoxia/drug effects , Cell Survival/drug effects , Nanoparticles/chemistry
19.
Theranostics ; 14(6): 2367-2378, 2024.
Article in English | MEDLINE | ID: mdl-38646652

ABSTRACT

The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation. With a comprehensive assessment tailored to an individual's unique clinical profile, AI algorithms promise to enhance patient risk classification, thereby benefiting the alignment of patient needs with the most appropriate treatment plans. By uncovering potential factors unseeable to the human eye, such as intrinsic variations in tumor radiosensitivity or molecular profile, AI software has the potential to revolutionize the prediction of response heterogeneity. For accurate and efficient dosimetry calculations, AI technology offers significant advantages by providing customized phantoms and streamlining complex mathematical algorithms, making personalized dosimetry feasible and accessible in busy clinical settings. AI tools have the potential to be leveraged to predict and mitigate treatment-related adverse events, allowing early interventions. Additionally, generative AI can be utilized to find new targets for developing novel radiopharmaceuticals and facilitate drug discovery. However, while there is immense potential and notable interest in the role of AI in theranostics, these technologies do not lack limitations and challenges. There remains still much to be explored and understood. In this study, we investigate the current applications of AI in theranostics and seek to broaden the horizons for future research and innovation.


Subject(s)
Artificial Intelligence , Neoplasms , Precision Medicine , Humans , Precision Medicine/methods , Precision Medicine/trends , Neoplasms/diagnosis , Neoplasms/therapy , Algorithms , Theranostic Nanomedicine/methods , Theranostic Nanomedicine/trends
20.
Theranostics ; 14(6): 2464-2488, 2024.
Article in English | MEDLINE | ID: mdl-38646648

ABSTRACT

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted drug delivery to the emergence of personalized medicine, theranostics has benefited from advances in imaging technologies, molecular biology, and nanomedicine. Furthermore, we emphasize pertinent illustrations showcasing that revolutionary strategies in cancer management enhance diagnostic accuracy and provide targeted therapies customized for individual patients, thereby facilitating the implementation of personalized medicine. Finally, we describe future perspectives on current challenges, emerging topics, and advances in the field.


Subject(s)
Neoplasms , Precision Medicine , Theranostic Nanomedicine , Humans , Neoplasms/therapy , Neoplasms/diagnosis , Theranostic Nanomedicine/methods , Precision Medicine/methods , Drug Delivery Systems/methods , Nanomedicine/methods , History, 20th Century , Animals , History, 21st Century
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