ABSTRACT
We have developed a micellar formulation of anticancer drugs based on chitosan and heparin grafted with lipoic and oleic acids that can release the cytotoxic cargo (doxorubicin) in response to external stimuli, such as increased glutathione concentration-a hallmark of cancer. Natural polysaccharides (heparin and chitosan) provide the pH sensitivity of the nanocarrier: the release of doxorubicin (Dox) is enhanced in a slightly acidic environment (tumor microenvironment). Fatty acid residues are necessary for the formation of nanoparticles (micelles) and solubilization of cytostatics in a hydrophobic core. Lipoic acid residues provide the formation of a labile S-S cross-linking between polymer chains (the first variant) or covalently attached doxorubicin molecules through glutathione-sensitive S-S bridges (the second variant)-both determine Redox sensitivity of the anticancer drugs carriers stable in blood circulation and disintegrate after intracellular uptake in the tumor cells. The release of doxorubicin from micelles occurs slowly (20%/6 h) in an environment with a pH of 7.4 and the absence of glutathione, while in a slightly acidic environment and in the presence of 10 mM glutathione, the rate increases up to 6 times, with an increase in the effective concentration up to 5 times after 7 h. The permeability of doxorubicin in micellar formulations (covalent S-S cross-linked and not) into Raji, K562, and A875 cancer cells was studied using FTIR, fluorescence spectroscopy and confocal laser scanning microscopy (CLSM). We have shown dramatically improved accumulation, decreased efflux, and increased cytotoxicity compared to doxorubicin control with three tumor cell lines: Raji, K562, and A875. At the same time, cytotoxicity and permeability for non-tumor cells (HEK293T) are significantly lower, increasing the selectivity index against tumor cells by several times.
ABSTRACT
Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Animals , Mice , Oxaliplatin/therapeutic use , Photothermal Therapy , Phototherapy/methods , Neoplasms/drug therapy , Immunotherapy , Cell Line, TumorABSTRACT
The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.
Subject(s)
Head and Neck Neoplasms , Nanoparticles , Animals , Mice , Cell Line, Tumor , Gold , Head and Neck Neoplasms/drug therapy , Hyaluronic Acid , Nanoparticles/therapeutic use , Phototherapy , Squamous Cell Carcinoma of Head and Neck/drug therapyABSTRACT
Many efforts have been made to develop near-infrared (NIR) fluorescent dyes with high efficiency for the NIR laser-induced phototherapy of cancer. However, the low tumor targetability and high nonspecific tissue uptake of NIR dyes in vivo limit their applications in preclinical cancer imaging and therapy. Among the various NIR dyes, squaraine (SQ) dyes are widely used due to their high molar extinction coefficient, intense fluorescence, and excellent photostability. Previously, benzoindole-derived SQ (BSQ) was prepared by incorporating carboxypentyl benzoindolium end groups into a classical SQ backbone, followed by conjugating with cyclic RGD peptides for tumor-targeted imaging. In this study, we demonstrate that the structure-inherent tumor-targeting BSQ not only shows a high fluorescence quantum yield in serum but also exhibits superior reactive oxygen species (ROS) generation capability under the 671 nm laser irradiation for effective photodynamic therapy (PDT) in vitro and in vivo. Without targeting ligands, the BSQ was preferentially accumulated in tumor tissue 24 h post-injection, which was the optimal timing of the laser irradiation to induce increments of ROS production. Therefore, this work provides a promising strategy for the development of photodynamic therapeutic SQ dyes for targeted cancer therapy.
Subject(s)
Cyclobutanes , Neoplasms , Phenols , Photochemotherapy , Humans , Reactive Oxygen Species , Fluorescence , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Fluorescent DyesABSTRACT
Mitochondria-targeting photothermal therapy could significantly enhance the tumor cell killing effect. However, since therapeutic reagents need to overcome a series of physiological obstacles to arrive at mitochondria accurately, precise mitochondria-targeting photothermal therapy still faces great challenges. In this study, we developed a self-delivery nanoplatform that specifically targeted the mitochondria of tumor cells for precise photothermal therapy. Photothermal agent IR780 was encapsulated by amphiphilic apoptotic peptide KLA with mitochondria-targeting ability to form nanomicelle KI by self-assembly through hydrophilic and hydrophobic interactions. Subsequently, negatively charged tumor-targeting polymer HA was coated on the surface of KI through electrostatic interactions, to obtain tumor mitochondria-targeting self-delivery nanoplatform HKI. Through CD44 receptor-mediated recognition, HKI was internalizated by tumor cells and then disassembled in an acidic environment with hyaluronidase in endosomes, resulting in the release of apoptotic peptide KLA and photothermal agent IR780 with mitochondria anchoring capacity, which achieved precise mitochondria guidance and destruction. This tumor mitochondria-targeting self-delivery nanoplatform was able to effectively deliver photothermal agents and apoptotic peptides to tumor cell mitochondria, resulting in precise destruction to mitochondria and enhancing tumor cell inhibition at the subcellular organelle level.
Subject(s)
Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Peptides , Mitochondria , Apoptosis , Nanoparticles/chemistry , Cell Line, Tumor , PhototherapyABSTRACT
Nanotechnology-based strategy has recently drawn extensive attention for the therapy of malignant tumors due to its distinct strengths in cancer diagnosis and treatment. However, the limited intratumoral permeability of nanoparticles is a major hurdle to achieving the desired effect of cancer treatment. Due to their superior cargo towing and reliable penetrating property, micro-/nanomotors (MNMs) are considered as one of the most potential candidates for the coming generation of drug delivery platforms. Here, near-infrared (NIR)-actuated biomimetic nanomotors (4T1-JPGSs-IND) are fabricated successfully and we demonstrate that 4T1-JPGSs-IND selectively accumulate in homologous tumor regions due to the effective homing ability. Upon laser irradiation, hyperthermia generated by 4T1-JPGSs-IND leads to self-thermophoretic motion and photothermal therapy (PTT) to ablate tumors with a deep depth, thereby improving the photothermal therapeutic effect for cancer management. The developed nanomotor system with multifunctionalities exhibits promising potential in biomedical applications to fight against various diseases.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Phototherapy , Biomimetics , Neoplasms/therapy , Cell Line, TumorABSTRACT
Imaging-guided photothermal therapy (PTT) for cancers recently gathered increasing focus thanks to its precise diagnosis and potent therapeutic effectiveness. Croconaine (CR) dyes demonstrate potential in expanding utility for near infrared (NIR) dyes in bio-imaging/theranostics. However, reports on CR dyes for PTT are scarce most likely due to the short of the efficacious delivery strategies to achieve specific accumulation in diseased tissues to induce PTT. Extracellular vesicles (EVs) are multifunctional nanoparticle systems that function as safe platform for disease theragnostics, which provide potential benefits in extensive biomedical applications. Here, we developed a novel delivery system for photothermal molecules based on a CR dye that exerts photothermal activity through CDH17 nanobody-engineered EVs. The formed CR@E8-EVs showed strong NIR absorption, excellent photothermal performance, good biological compatibility and superb active tumor-targeting capability. The CR@E8-EVs can not only visualize and feature the tumors through CR intrinsic property as a photoacoustic imaging (PAI) agent, but also effectively retard the tumor growth under laser irradiation to perform PTT. It is expected that the engineered EVs will become a novel delivery vehicle of small organic photothermal agents (SOPTAs) in future clinical PTT applications.
Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Humans , Photothermal Therapy , Phototherapy/methods , Theranostic Nanomedicine/methods , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Coloring Agents , Photoacoustic Techniques/methods , Cell Line, TumorABSTRACT
Single tumor treatment method usually has some defects, which makes it difficult to achieve good therapeutic effect. The ingenious combination of multiple tumor treatment methods on a single nanoplatform to achieve multifunctional treatment can effectively improve the efficiency of treatment. The targeted modification of nanomaterials can augment the precision of nanotherapeutic drugs in tumor treatment. Herein, a multifunctional nanoplatform (CeO2@CuS@PDA-FA) based on cerium dioxide nanoparticles engineered with copper sulfide (CeO2@CuS) has been constructed for synergistic photothermal therapy (PTT) and chemodynamic therapy (CDT). The CeO2@CuS were coated using polydopamine (PDA), and the modification of PDA surface by folic acid, in order to achieve the targeted effect for tumors. The localized hyperthermia induced by PTT can further improve the CDT efficiency of the nanoplatform, leading to a PTT/CDT synergistic effect. The nanoplatform possessed the capability of cancer cell-targeted and achieved better therapeutic efficacyin vitro. This work provided a new strategy for combined multifunctional theranostic platform and shows strong potential in practical applications.
Subject(s)
Electric Stimulation Therapy , Neoplasms , Phototherapy , Indoles , Photothermal Therapy , Neoplasms/drug therapyABSTRACT
Photothermal therapy (PTT) systems typically do not possess intrinsic tumor-targeting capability, resulting in indiscriminate thermal damage to both cancer and normal cells. Herein, a low-density lipoprotein (LDL)-based nanosystem (denoted as MTTQ@LDL) is reported for targeted photothermal killing of cancer cells. Such a nanosystem is fabricated by reconstituting the lipophilic core of LDL with an organic photothermal agent MTTQ. The reconstitution process improves the supramolecular photothermal effects of MTTQ assemblies, which contributes to the significantly enhanced photothermal conversion efficiency (41.3% vs. 16.2%). MTTQ@LDL can actively target LDL receptor-overexpressed cancer cells via receptor-mediated endocytosis, enabling the selective killing of cancer cells over normal cells (98% vs. 7%) post-NIR irradiation. Reconstituted LDL can serve as a promising platform for targeted delivery of functional materials, holding great promise in tumor eradication in vivo.
Subject(s)
Nanoparticles , Neoplasms , Humans , Phototherapy , Lipoproteins, LDL , Neoplasms/drug therapy , Cell Line, TumorABSTRACT
The fast renal clearance of hydrophilic small molecular anticancer drugs and ultrasmall nanoparticles (NPs) results in the low utilization rate and certain side effects, thus improving the tumor targeting is highly desired but faces great challenges. A novel and general ß-cyclodextrin (CD) aggregation-induced assembly strategy to fabricate doxorubicin (DOX) and CD-coated NPs (such as Au) co-encapsulated pH-responsive nanocomposites (NCs) is proposed. By adding DOX×HCl and reducing pH in a reversed microemulsion system, hydrophilic CD-coated AuNPs rapidly assemble into large NCs. Then in situ polymerization of dopamine and sequentially coordinating with Cu2+ on the surface of NCs provide extra weak acid responsiveness, chemodynamic therapy (CDT), and improved biocompatibility as well as stability. The subsequent tumor microenvironment responsive dissociation notably improves their passive tumor targeting, bioavailability, imaging, and therapeutic capabilities, as well as facilitates their internalization by tumor cells and metabolic clearance, thereby reducing side effects. The combination of polymerized dopamine and assembled AuNPs reinforces photothermal capability, thus further boosting CDT through thermally amplifying Cu-catalyzed Fenton-like reaction. Both in vitro and in vivo studies confirm the desirable outcomes of these NCs as photoacoustic imaging guided trimodal (thermally enhanced CDT, photothermal therapy, and chemotherapy) synergistic tumor treatment agents with minimal systemic toxicity.
Subject(s)
Hyperthermia, Induced , Metal Nanoparticles , Nanoparticles , Neoplasms , Humans , Gold , Dopamine/therapeutic use , Hyperthermia, Induced/methods , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Nanoparticles/chemistry , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Multimodal phototheranostics on the basis of a single molecule with one-for-all characteristics represents a convenient approach for effective cancer treatment. In this report, a versatile molecule featured by aggregation-induced emission, namely DHTDP, synchronously enabling second near-infrared (NIR-II) fluorescence emission and efficient photothermal conversion is developed by elaborate structural modulation. By camouflaging DHTDP nanoparticles with cancer cell membrane, the resultant biomimetic nanoparticles exhibit significantly both facilitated delivery efficiency and homologous targeting capability, and afford precise imaging guidance and maximize therapeutic outcomes in form of NIR-II fluorescence imaging (FLI)-photoacoustic imaging (PAI)-photothermal imaging (PTI) trimodal imaging-guided photothermal therapy (PTT). This study presents the first example of biomimetic multimodal phototheranostics loaded by homogeneity-targeting cell membrane, thus brings a new insight into the exploration of superior phototheranostics for practical cancer theranostics.
Subject(s)
Nanoparticles , Neoplasms , Photoacoustic Techniques , Humans , Theranostic Nanomedicine/methods , Phototherapy/methods , Cell Membrane/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Multimodal Imaging , Nanoparticles/chemistry , Cell Line, Tumor , Photoacoustic Techniques/methodsABSTRACT
Prostate cancer (PCa) routinely employs magnetic resonance (MR) imaging, while metastatic PCa needs more complicated detection methods for precise localization. The inconvenience of using different methods to detect PCa and its metastases in patients and the limitations of single-mode imaging have brought great challenges to clinicians. Meanwhile, clinical treatments for metastatic PCa are still limited. Herein, we report a targeted theranostic platform of Au/Mn nanodots-luteinising hormone releasing hormone (AMNDs-LHRH) nano-system for multi-mode imaging guided photothermal therapy of PCa. The nano-system not only can simultaneously target Gonadotropin-Releasing Hormone Receptor (GnRH-R) positive PCa and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence (FL) visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. Meanwhile, the AMNDs-LHRH with promising targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic PCa. The AMNDs-LHRH nano-system guarantees the diagnostic accuracy and enhanced therapeutic effect, which provides a promising platform for clinical diagnosis and treatment of metastatic PCa. STATEMENT OF SIGNIFICANCE: Accurate clinical diagnosis and treatment of prostate cancer and its metastases is challenging. A targeted theranostic platform of AMNDs-LHRH nano-system for multi-mode imaging (FL/CT/MR) guided photothermal therapy of metastatic prostate cancer has been reported. The nano-system not only can simultaneously target prostate cancer and its metastases for accurate preoperative CT/MR diagnosis, but also possesses fluorescence visualization navigated surgery, demonstrating its potential application in clinical cancer detection and surgery guidance. The nano-system with great targeting and photothermal conversion ability significantly improve the photothermal therapy effect of metastatic prostate cancer. Overall, the AMNDs-LHRH nano-system integrates tumor targeting, multi-mode imaging and enhanced therapeutic effect, which can provide an effective strategy for the clinical diagnosis and treatment of metastatic PCa.
Subject(s)
Photothermal Therapy , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Phototherapy , Magnetic Resonance Imaging/methods , Gonadotropin-Releasing Hormone , Cell Line, TumorABSTRACT
Phototherapies, in the form of photodynamic therapy (PDT) and photothermal therapy (PTT), have great application prospects in the field of biomedical science due to high precision and non-invasiveness. Because of the limited therapeutic efficacy of single phototherapy, researchers start to focus on combined PTT-PDT. Here, we designed a composite nanomaterial for PTT-PDT. H-TiO2 mesoporous spheres were prepared by sol-gel method and hydrogenation treatment. After modification with polydopamine (PDA), they were combined with indocyanine green (ICG) and NPe6 photosensitizers and coated by thermosensitive liposomes to prepare H-TiO2 @PDA@ICG@NPe6 @Lipo nanocomposite component. The results indicated a substantial improvement of the component in the aspects of spectral response range, photothermal conversion efficiency and light absorption performance by modification and photosensitizers, in the absence of any toxicities on cells. Thermal induction and sequential irradiation with 808 nm and 664 nm lasers induced the aggregation of H-TiO2 @PDA@ICG@NPe6 @Lipo at the tumor site to generate hyperthermia and massive reactive oxygen species (ROS), resulting in decreased cell activity or even cell apoptosis and restrained growth of allograft tumors. These findings underscore the favorable effects of H-TiO2 @PDA@ICG@NPe6 @Lipo on the combined phototherapies and provide approaches for the development of nano-drugs in the context of liver cancer.
Subject(s)
Hyperthermia, Induced , Liver Neoplasms , Nanocomposites , Nanoparticles , Photochemotherapy , Humans , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Hyperthermia, Induced/methods , Phototherapy/methods , Indocyanine Green/pharmacology , Liver Neoplasms/drug therapy , Nanoparticles/therapeutic use , Cell Line, TumorABSTRACT
The combination of chemotherapy and phototherapy has received tremendous attention in multimodal cancer therapy. However, satisfactory therapeutic outcomes of chemo-photothermal therapy (chemo-PTT) still remain challenging. Herein, a biocompatible smart nanoplatform based on benzothiazole-linked conjugated polymer nanoparticles (CPNs) is rationally designed, for effectively loading doxorubicin (DOX) and Mo-based polyoxometalate (POM) through both dynamic chemical bond and intermolecular interactions, with an expectation to obtain new anticancer drugs with multiple stimulated responses to the tumor microenvironment (TME) and external laser irradiation. Controlled drug release of DOX from the obtained nanoformulation (CPNs-DOX-PEG-cRGD-BSA@POM) triggered by both endogenous stimulations (GSH and low pH) and exogenous laser irradiation has been well demonstrated by pharmacodynamics investigations. More intriguingly, incorporating POM into the nanoplatform not only enables the nanomedicine to achieve mild hyperthermia but also makes it exhibit self-assembly behavior in acidic TME, producing enhanced tumor retention. Benefiting from the versatile functions, the prepared CPNs-DOX-PEG-cRGD-BSA@POM exhibited excellent tumor targeting and therapeutic effects in murine xenografted models, showing great potential in practical cancer therapy.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Animals , Mice , Photothermal Therapy , Polymers , Doxorubicin/chemistry , Phototherapy , Neoplasms/pathology , Nanoparticles/chemistry , Benzothiazoles , Tumor MicroenvironmentABSTRACT
Radiation therapy has been widely used in the clinical treatment of tumors. Due to the low radiation absorption of tumors, a high dose of ionizing radiation is often required during radiotherapy, which causes serious damage to normal tissues near tumors. Boron neutron capture therapy (BNCT) is more targeted than conventional radiotherapy. To improve the therapeutic effect of cancer, albumin was selected as the drug carrier to wrap the fluorescent tracer boron drug BS-CyP and prepare the nanoparticles. Then, we developed a novel tumor-targeting nano-boron drug by using hyaluronic acid to modify the nanoparticles. We found that BS-CyP albumin nanoparticles modified with hyaluronic acid effectively delayed drug release and enhanced the aggregation, in tumors, showing good safety with no obvious toxicity to cells and mice. This study confirmed the advantages of boron drugs modified with hyaluronic acid targeting tumors and may provide a reference for BNCT.
Subject(s)
Boron Neutron Capture Therapy , Nanoparticles , Neoplasms , Animals , Mice , Hyaluronic Acid , Boron/therapeutic use , Neoplasms/drug therapy , Boron CompoundsABSTRACT
Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.
Subject(s)
Fluorescent Dyes , Neoplasms , Photosensitizing Agents , Phototherapy , Serum Albumin, Bovine , Humans , Cell Line, Tumor , Fluorescent Dyes/chemistry , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Optical Imaging/methods , Phototherapy/methods , Serum Albumin, Bovine/chemistryABSTRACT
Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumors. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye make it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, Probe-1 is developed to enhance PAI and PTT of liver tumors due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displays a 4.6-fold higher PAI signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 shows extended retention time (10 vs 6 h) and 2.1-fold higher PAI signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increase 18 °C (Tmax : 55 °C) with a 3.3-fold decreased volume while that in Group Probe-2 mildly increase 9.8 °C (Tmax : 46.8 °C) with a 4.3-fold increased volume. It is envisioned that this smart self-assembly strategy can be easily adjusted for PAI and PTT of more tumors.
Subject(s)
Liver Neoplasms , Nanoparticles , Neoplasms , Photoacoustic Techniques , Humans , Photothermal Therapy , Photoacoustic Techniques/methods , Neoplasms/diagnostic imaging , Neoplasms/therapy , Nanoparticles/therapeutic use , Phototherapy/methods , Liver Neoplasms/therapyABSTRACT
Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Mice , Animals , Chlorambucil/pharmacology , Tissue Distribution , Fluorescent Dyes/chemistry , Phototherapy , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Ionophores , Water , Neoplasms/diagnostic imaging , Neoplasms/drug therapyABSTRACT
Targeted tumor imaging can effectively enable image-guided surgery and precise cancer therapy. Finding the right combination of anticancer drugs and near-infrared (NIR) fluorophores is the key to targeted photothermal cancer treatment. In this study, a tumor-targetable NIR fluorophore conjugate with rapid body clearance was developed for accurate tumor imaging and effective photothermal therapy (PTT). The methotrexate (MTX) and zwitterionic NIR fluorophore conjugate (MTX-ZW) were prepared by conjugating a folate antagonist MTX with an aminated ZW800-1 analog to increase the tumor targetability for NIR laser-based PTT of cancer. The MTX, known as a poor tumor-selective drug, showed high tumor accumulation and rapid background clearance after conjugation with the highly water-soluble zwitterionic NIR fluorophore up to 4 h post-injection. The photothermal energy was generated from the MTX-ZW conjugate to induce necrotic cell death in the targeted tumor site under 808 nm laser irradiation. Compared with the previously reported MTX conjugates, the MTX-ZW conjugate can be a great candidate for targeted tumor imaging and fluorescence-guided photothermal cancer therapy. Therefore, these results provide a strategy for the design of drug-fluorophore conjugates and elaborate therapeutic platforms for cancer phototherapy.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Photothermal Therapy , Methotrexate/pharmacology , Neoplasms/diagnostic imaging , Neoplasms/therapy , Fluorescent Dyes , Antineoplastic Agents/pharmacology , IonophoresABSTRACT
Quantum Dots (QDs) are fluorescent nanoparticles known for their exceptional optical properties, i.e., high fluorescence emission, photostability, narrow emission spectrum, and broad excitation wavelength. These properties make QDs an exciting choice for bioimaging applications, notably in cancer imaging. Challenges lie in their ability to specifically label targeted cells. Numerous studies have been carried out with QDs coupled to various ligands like peptides, antibodies, aptamers, etc., to achieve efficient targeting. Most studies were conducted in vitro with two-dimensional cell monolayers (n = 8902) before evolving towards more sophisticated models. Three-dimensional multicellular tumor models better recapitulate in vivo conditions by mimicking cell-to-cell and cell-matrix interactions. To date, only few studies (n = 34) were conducted in 3D in vitro models such as spheroids, whereas these models could better represent QDs behavior in tumors compared to monolayers. Thus, the purpose of this review is to present a state of the art on the studies conducted with Quantum Dots on spheroid models for imaging and phototherapy purposes.