ABSTRACT
The efficiency of photodynamic therapy (PDT) is related to the subcellular localization of photosensitizers (PSs) because organelles are associated with many fundamental life-sustaining activities. In this work, we synthesized a PS (CN) based on curcumin (CUR) and obtained enhanced PDT efficiency by simultaneously targeting lipid droplets (LDs) and the endoplasmic reticulum (ER). Compared with CUR, CN with a D-π-A-π-D structure possessed stronger intramolecular charge transfer features, resulting in longer absorption and emission wavelengths. In cell imaging experiments of CN using a confocal laser scanning microscope, a bright green emission in LDs and a weak orange emission in the ER were simultaneously observed due to its sensitivity to polarity. Surprisingly, CN with low singlet oxygen yields (0.13) exhibited an excellent photodynamic effect. Further experimental results showed that the phototoxicity of CN resulted in apoptosis by destroying the ER and ferroptosis by oxidizing polyunsaturated fatty acids (PUFAs) in LDs. This work paves the way for developing more effective photosensitizers with superior dual-targeting specificity.
Subject(s)
Curcumin , Photochemotherapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Curcumin/pharmacology , Photochemotherapy/methods , Endoplasmic Reticulum , Singlet OxygenABSTRACT
Developing nanoplatforms integrating superior fluorescence imaging ability in second near-infrared (NIR-II) window and tumor microenvironment responsive multi-modal therapy holds great potential for real-time feedback of therapeutic efficacy and optimizing tumor inhibition. Herein, we developed a pH-sensitive pyrrolopyrrole aza-BODIPY-based amphiphilic molecule (PTG), which has a balanced NIR-II fluorescence brightness and photothermal effect. PTG is further co-assembled with a vascular disrupting agent (known as DMXAA) to prepare PTDG nanoparticles for combined anti-vascular/photothermal therapy and real-time monitoring of the tumor vascular disruption. Each PTG molecule has an active PT-3 core which is linked to two PEG chains via pH-sensitive ester bonds. The cleavage of ester bonds in the acidic tumor environment would tricker releases of DMXAA for anti-vascular therapy and further assemble PT-3 cores into micrometer particles for long term monitoring of the tumor progression. Furthermore, benefiting from the high brightness in the NIR-II region (119.61 M-1 cm-1) and long blood circulation time (t1/2 = 235.6 min) of PTDG nanoparticles, the tumor vascular disrupting process can be in situ visualized in real time during treatment. Overall, this study demonstrates a self-assembly strategy to build a pH-responsive NIR-II nanoplatform for real-time monitoring of tumor vascular disruption, long-term tracking tumor progression and combined anti-vascular/photothermal therapy.
Subject(s)
Nanoparticles , Neoplasms , Humans , Photothermal Therapy , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/pathology , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Esters , Cell Line, Tumor , Phototherapy/methods , Tumor MicroenvironmentABSTRACT
Recently, many organic optoelectronic materials (OOMs), especially those used in organic light-emitting diodes (OLEDs), organic solar cells (OSCs), and organic field-effect transistors (OFETs), are explored for biomedical applications including imaging and photoexcited therapies. In this review, recently developed OOMs for fluorescence imaging, photoacoustic imaging, photothermal therapy, and photodynamic therapy, are summarized. Relationships between their molecular structures, nanoaggregation structures, photophysical mechanisms, and properties for various biomedical applications are discussed. Mainly four kinds of OOMs are covered: thermally activated delayed fluorescence materials in OLEDs, conjugated small molecules and polymers in OSCs, and charge-transfer complexes in OFETs. Based on the OOMs unique optical properties, including excitation light wavelength and exciton dynamics, they are respectively exploited for suitable biomedical applications. This review is intended to serve as a bridge between researchers in the area of organic optoelectronic devices and those in the area of biomedical applications. Moreover, it provides guidance for selecting or modifying OOMs for high-performance biomedical uses. Current challenges and future perspectives of OOMs are also discussed with the hope of inspiring further development of OOMs for efficient biomedical applications.
ABSTRACT
Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.
Subject(s)
Nanoparticles , Neoplasms , Humans , Fluorescent Dyes/pharmacology , Phototherapy , Optical Imaging/methodsABSTRACT
Fluorescence (FL) bioimaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides improved imaging quality and high resolution for diagnosis of deep-seated tumors. However, integrating FL bioimaging and photothermal therapy (PTT) in a single photoactive molecule exhibits a great challenge because a dramatic increase of PTT in the NIR-II window benefitting from the nonradiative decay will sacrifice the fluorescence brightness that is unfavorable for FL bioimaging. Therefore, balancing the radiative decay and nonradiative decay is an effective and rational design strategy. Herein, four NIR-II xanthene dyes (CL1-CL4) are synthesized with maximal emission beyond 1200 nm under 1064 nm excitation. CL4 exhibits the largest fluorescence quantum yield and a significant fluorescence enhancement after complexation with fetal bovine serum (FBS). As-prepared CL4/FBS has a maximal emission of 1235 nm and a high photothermal conversion efficiency of 36% under 1064 nm excitation. Bright and refined tumor vessels with a fine resolution of 0.23 mm can be clearly distinguished by CL4/FBS. In vivo studies show that a balanced utilization of fluorescence and photothermy in the NIR-II window is successfully achieved with superior biocompatibility. This efficient strategy provides promising avenue for precise theranostics of deep tumors.
Subject(s)
Nanoparticles , Neoplasms , Angiography , Coloring Agents , Fluorescent Dyes , Humans , Neoplasms/diagnostic imaging , Neoplasms/therapy , Phototherapy , Photothermal Therapy , Theranostic Nanomedicine/methods , XanthenesABSTRACT
Rechargeable magnesium batteries (RMBs) are promising candidates to replace currently commercialized lithium-ion batteries (LIBs) in large-scale energy storage applications owing to their merits of abundant resources, low cost, high theoretical volumetric capacity, etc. However, the development of RMBs is still facing great challenges including the incompatibility of the electrolyte and the lack of suitable cathode materials with high reversible capacity and fast kinetics of Mg2+ . While tremendous efforts have been made to explore compatible electrolytes and appropriate electrode materials, the rational design of unconventional Mg-based battery systems is another effective strategy for achieving high electrochemical performance. This review specifically discusses the recent research progress of various Mg-based battery systems. First, the optimization of electrolyte and electrode materials for conventional RMBs is briefly discussed. Furthermore, various Mg-based battery systems, including Mg-chalcogen (S, Se, Te) batteries, Mg-halogen (Br2 , I2 ) batteries, hybrid-ion batteries, and Mg-based dual-ion batteries are systematically summarized. This review aims to provide a comprehensive understanding of different Mg-based battery systems, which can inspire latecomers to explore new strategies for the development of high-performance and practically available RMBs.
ABSTRACT
There has been much recent progress in the development of photothermal agents (PTAs) for biomedical and energy applications. Synthesis of organic PTAs typically involves noble metal catalysts and high temperatures. On the other hand, photochemical synthesis, as an alternative and green chemical technology, has obvious merits such as low cost, energy efficiency, and high yields. However, photochemical reactions have rarely been employed for the synthesis of PTAs. Herein, a facile and high-yield photochemical reaction is exploited for synthesizing nonplanar small molecules (NSMs) containing strong Michler's base donors and a tricyanoquinodimethane acceptor as high-performance PTAs. The synthesized NSMs show interesting photophysical properties including good absorption for photons of over 1000 nm wavelength, high near-infrared extinction coefficients, and excellent photothermal performance. Upon assembling the NSMs into nanoparticles (NSMN), they exhibit good biocompatibility, high photostability, and excellent photothermal conversion efficiency of 75%. Excited-state dynamic studies reveal that the NSMN has ultrafast nonradiative decay after photoexcitation. With these unique properties, the NSMN achieves efficient in vivo photoacoustic imaging and photothermal tumor ablation. This work demonstrates the superior potential of photochemical reactions for the synthesis of high-performance molecular PTAs.
Subject(s)
Phototherapy , Theranostic Nanomedicine , Nanoparticles , Photoacoustic TechniquesABSTRACT
Effective and noninvasive diagnosis and prompt treatment of early-stage hepatocellular carcinoma (HCC) are urgently needed to reduce its mortality rate. Herein, the integration of high-resolution diagnostic second near-infrared (NIR-II) photoacoustic computed tomography (PACT) and imaging-guided targeted photothermal ablation of orthotopic small HCC (SHCC) is presented for the first time, which was enabled by a plasmonic platinum (Pt)-doped polydopamine melanin-mimic nanoagent. As designed, an antibody-modified nanoagent (designated Pt@PDA-c) with a plasmonic blackbody-like NIR absorption and superior photothermal conversion efficiency (71.3%) selectively targeted and killed CXCR4-overexpressing HCC (HepG2) cells, which was validated in in vitro experiments. The targeted accumulation properties of Pt@PDA-c in vivo were previously recognized by demonstrating effective NIR-II PA imaging and photothermal ablation in a subcutaneous HCC mouse model. Subsequently, with real-time quantitative guidance by PACT for the accurate diagnosis of intraabdominal SHCC (approximately 4 mm depth), the effective and noninvasive photothermal ablation of SHCCs was successfully demonstrated in an orthotopic tumor-bearing mouse model without damaging adjacent liver tissues. These results show a great potential of NIR-II PACT-guided noninvasive photothermal therapy as an innovative phototheranostic approach and expand the biomedical applications of melanin-mimic materials. STATEMENT OF SIGNIFICANCE: In this paper, we report the first diagnostic NIR-II photoacoustic computed tomography (PACT)-guided noninvasive photothermal ablation of small hepatocellular carcinoma (SHCC) located in deep tissues in orthotopic tumor-bearing mice; this process is empowered by a polydopamine-based melanin-mimic tumor-targeting nanoagent doped with plasmonic platinum that provides superior NIR-II (1064 nm) absorption and photothermal conversion efficiency of 71.3%. Following surface modification with anti-CXCR4 antibodies, the nanoagent (namely Pt@PDA-c) can selectively target CXCR4-overexpressed HepG2 carcinoma cells and tumor lesions, and serve as the theranostic agent for both NIR-II PACT-based diagnosis of orthotopic SHCC (diameter less than 5 mm) and efficient NIR-II PTT in vivo. This study may also extend the potential of melanin-derived blackbody materials for optical-biomedical and water distillation applications.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Neoplasms , Photoacoustic Techniques , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Melanins , Mice , Phototherapy , Theranostic Nanomedicine , Tomography, X-Ray ComputedABSTRACT
Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350â nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040â nm and achieves a good photothermal conversion efficiency of 42 % under 1064â nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.
Subject(s)
Anti-Bacterial Agents/pharmacology , Nanoparticles/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/radiation effects , Benzene Derivatives/chemistry , Benzene Derivatives/pharmacology , Benzene Derivatives/radiation effects , Escherichia coli/drug effects , Infrared Rays , Microbial Sensitivity Tests , Nanoparticles/radiation effects , Nitriles/chemistry , Nitriles/pharmacology , Nitriles/radiation effects , Perylene/chemistry , Perylene/pharmacology , Perylene/radiation effects , Polycyclic Compounds/chemistry , Polycyclic Compounds/pharmacology , Polycyclic Compounds/radiation effects , Solubility , Staphylococcus aureus/drug effects , Static Electricity/adverse effects , Sulfhydryl Compounds/chemistry , Sulfhydryl Compounds/pharmacology , Sulfhydryl Compounds/radiation effects , Water/chemistryABSTRACT
Pharmaceutical evaluations of nanomedicines are of great significance for their further launch into industry and clinic. Near-infrared (NIR) fluorescence imaging plays essential roles in preclinical drug development by providing important insights into the biodistributions of drugs in vivo with deep tissue penetration and high spatiotemporal resolution. However, NIR-II fluorescence imaging has rarely been exploited for in vivo real-time pharmaceutical evaluations of nanomedicine. Herein, we developed a highly emissive NIR-II luminophore to establish a versatile nanoplatform to noninvasively monitor the in vivo metabolism of nanomedicines bound various polyethylene glycol (PEG) ligands in a real-time manner. An alternative D-A-D conjugated oligomer (DTTB) was synthesized to achieve NIR-II emission peaked at â¼1050 nm with high fluorescence QYs of 13.4% and a large absorption coefficient. By anchoring with the DTTB molecule, intrinsically fluorescent micelles were fabricated and bound with PEG ligands at various chain lengths. In vivo NIR-II fluorescence and photoacoustic imaging results revealed that an appropriate PEG chain length could effectively contribute to the longer blood circulation and better tumor targeting. In vivo therapeutic experiments also confirmed the optimized nanomedicines have efficient photothermal elimination of tumors and good biosafety. This work offered an alternative highly fluorescent NIR-II material and demonstrated a promising approach for real-time pharmaceutical evaluation of nanomedicine in vivo.
Subject(s)
Hyperthermia, Induced , Neoplasms , Photoacoustic Techniques , Humans , Ligands , Nanomedicine , Neoplasms/therapy , Phototherapy , Polyethylene Glycols , Theranostic NanomedicineABSTRACT
Hypocrellin B (HB) derived from naturally produced hypocrellins has attracted considerable attention in photodynamic therapy (PDT) because of its excellent photosensitive properties. However, the weak absorption within a "phototherapy window" (600-900â nm) and poor water solubility of HB have limited its clinical application. In this study, two HB derivatives (i. e., HE and HF) were designed and synthesized for the first time by introducing two different substituent groups into the HB structure. The obtained derivatives showed a broad absorption band covering the near-infrared (NIR) region, NIR emission (peaked at 805â nm), and singlet oxygen quantum yields of 0.27/0.31. HE-PEG-NPs were also prepared using 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) to achieve excellent dispersion in water and further explored their practical applications. HE-PEG-NPs not only retained their 1 O2 -generating ability, but also exhibited a photothermal conversion efficiency of 25.9%. In vitro and inâ vivo therapeutic results revealed that the synergetic effect of HE-PEG-NPs on PDT and photothermal therapy (PTT) could achieve a good performance. Therefore, HE-PEG-NPs could be regarded as a promising phototheranostic agent.
Subject(s)
Antineoplastic Agents/pharmacology , Perylene/analogs & derivatives , Phenol/pharmacology , Photosensitizing Agents/pharmacology , Photothermal Therapy , Quinones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Female , Infrared Rays , Mammary Neoplasms, Experimental/diagnostic imaging , Mammary Neoplasms, Experimental/drug therapy , Mice , Optical Imaging , Perylene/chemical synthesis , Perylene/chemistry , Perylene/pharmacology , Phenol/chemical synthesis , Phenol/chemistry , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Quinones/chemical synthesis , Quinones/chemistry , Theranostic NanomedicineABSTRACT
Extensive recent progress has been made on the design and applications of organic photothermal agents for biomedical applications because of their excellent biocompatibility comparing with inorganic materials. One major hurdle for the further development and applications of organic photothermal agents is the rarity of high-performance materials in the second near-infrared (NIR-II) window, which allows deep tissue penetration and causes minimized side effects. Up till now, there have been few reported NIR-II-active photothermal agents and their photothermal conversion efficiencies are relatively low. Herein, optical absorption of π-conjugated small molecules from the first NIR window to the NIR-II window is precisely regulated by molecular surgery of substituting an individual atom. With this technique, the first demonstration of a conjugated oligomer (IR-SS) with an absorption peak beyond 1000 nm is presented, and its nanoparticle achieves a record-high photothermal conversion efficiency of 77% under 1064 nm excitation. The nanoparticles show a good photoacoustic response, photothermal therapeutic efficacy, and biocompatibility in vitro and in vivo. This work develops a strategy to boost the light-harvesting efficiency in the NIR-II window for cancer theranostics, offering an important step forward in advancing the design and application of NIR-II photothermal agents.
Subject(s)
Diagnosis , Drug Design , Infrared Rays/therapeutic use , Phototherapy/methods , Small Molecule Libraries/therapeutic use , Temperature , Optical Phenomena , Polymerization , Small Molecule Libraries/chemistryABSTRACT
Multi-modality imaging-guided cancer therapy is considered as a powerful theranostic platform enabling simultaneous precise diagnosis and treatment of cancer. However, recently reported multifunctional systems with multiple components and sophisticate structures remain major obstacles for further clinical translation. In this work, a single-photomolecular theranostic nanoplatform is fabricated via a facile nanoprecipitation strategy. By encapsulating a semiconductor oligomer (IT-S) into an amphiphilic lipid, water-dispersible IT-S nanoparticles (IT-S NPs) are prepared. The obtained IT-S NPs have a very simple construction and possess ultra-stable near-infrared (NIR) fluorescence (FL)/photoacoustic (PA) dual-modal imaging and high photothermal conversion efficiency of 72.3%. Accurate spatiotemporal distribution profiles of IT-S NPs are successfully visualized by NIR FL/PA dual-modal imaging. With the comprehensive in vivo imaging information provided by IT-S NPs, tumor photothermal ablation is readily realized under precise manipulation of laser irradiation, which greatly improves the therapeutic efficacy without any obvious side effects. Therefore, the IT-S NPs allow high tumor therapeutic efficacy under the precise guidance of FL/PA imaging techniques and thus hold great potential as an effective theranostic platform for future clinical applications.
Subject(s)
Hyperthermia, Induced , Nanoparticles , Neoplasms , Photoacoustic Techniques , Cell Line, Tumor , Humans , Neoplasms/diagnostic imaging , Neoplasms/therapy , Optical Imaging , Phototherapy , Theranostic NanomedicineABSTRACT
Effective multimodality phototheranostics under deep-penetration laser excitation is highly desired for tumor medicine, which is still at a deadlock due to lack of versatile photosensitizers with absorption located in the long-wavelength region. Herein, we demonstrate a stable organic photosensitizer nanoparticle based on molecular engineering of benzo[c]thiophene (BT)-based photoactivated molecules with strong wavelength-tunable absorption in the near-infrared region. Via molecular design, the absorption and singlet oxygen generation of BT molecules would be reliably tuned. Importantly, the nanoparticles with a red-shifted absorption peak of 843 nm not only show over 10-fold reactive oxygen species yield compared with indocyanine green but also demonstrate a notable photothermal effect and photoacoustic signal upon 808 nm excitation. The in vitro and in vivo experiments substantiate good multimodal anticancer efficacy and imaging performance of BT theranostics. This work provides an organic photosensitizer nanoparticle with long-wavelength excitation and high photoenergy conversion efficiency for multimodality phototherapy.
Subject(s)
Nanoparticles , Photosensitizing Agents , Phototherapy , Reactive Oxygen Species , Theranostic NanomedicineABSTRACT
Due to their versatile applications, gold (Au) and silver (Ag) nanoparticles (NPs) have been synthesized by many approaches, including green processes using plant extracts for reducing metal ions. In this work, we propose to use plant extract with active biomedical components for NPs synthesis, aiming to obtain NPs inheriting the biomedical functions of the plants. By using leaves extract of Clerodendrum inerme (C. inerme) as both a reducing agent and a capping agent, we have synthesized gold (CI-Au) and silver (CI-Ag) NPs covered with biomedically active functional groups from C. inerme. The synthesized NPs were evaluated for different biological activities such as antibacterial and antimycotic against different pathogenic microbes (B. subtilis, S. aureus, Klebsiella, and E. coli) and (A. niger, T. harzianum, and A. flavus), respectively, using agar well diffusion assays. The antimicrobial propensity of NPs further assessed by reactive oxygen species (ROS) glutathione (GSH) and FTIR analysis. Biofilm inhibition activity was also carried out using colorimetric assays. The antioxidant and cytotoxic potential of CI-Au and CI-Ag NPs was determined using DPPH free radical scavenging and MTT assay, respectively. The CI-Au and CI-Ag NPs were demonstrated to have much better antioxidant in terms of %DPPH scavenging (75.85% ± 0.67% and 78.87% ± 0.19%), respectively. They exhibited excellent antibacterial, antimycotic, biofilm inhibition and cytotoxic performance against pathogenic microbes and MCF-7 cells compared to commercial Au and Ag NPs functionalized with dodecanethiol and PVP, respectively. The biocompatibility test further corroborated that CI-Ag and CI-Au NPs are more biocompatible at the concentration level of 1-50 µM. Hence, this work opens a new environmentally-friendly path for synthesizing nanomaterials inherited with enhanced and/or additional biomedical functionalities inherited from their herbal sources.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Antioxidants/pharmacology , Clerodendrum/chemistry , Plant Extracts/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Bacteria/drug effects , Biofilms/drug effects , Biphenyl Compounds/antagonists & inhibitors , Dose-Response Relationship, Drug , Fungi/drug effects , Gold/chemistry , Gold/pharmacology , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Picrates/antagonists & inhibitors , Plant Extracts/chemical synthesis , Plant Extracts/chemistry , Silver/chemistry , Silver/pharmacologyABSTRACT
Development of near-infrared-II (NIR-II) light responsive nano-agents with high photothermal stability, high photothermal conversion efficiency (PCE), and excellent biocompatibility for photoacoustic (PA) imaging-guided photothermal therapy (PTT) is of tremendous significance. In spite of the superiority of organic semiconducting polymer nanoparticles (OSPNs) in PA imaging-guided PTT, the limited absorption in the first NIR (NIR-I) window and metastable nanostructure of OSPNs resulting from commonly used preparation methods based on nanoprecipitation or reprecipitation compromise their in vivo phototheranostic performance. Herein we design and synthesize a novel NIR-II absorbing organic semiconducting polymer amphiphile (OSPA) to enhance the structural stability of OSPNs. With prominent optical properties, low toxicity, and a suitable size, OSPA not only efficiently labels and kills cancer cells under NIR-II irradiation but also accumulates at the tumor of living mice upon intravenous injection, allowing efficient NIR-II light-triggered phototheranostics toward tumor. The developed OSPA has promising potential for fabricating multifunctional nanoplatforms to enable multimodal theranostics.
Subject(s)
Nanoparticles , Photoacoustic Techniques , Polymers , Theranostic Nanomedicine , Animals , Infrared Rays , Mice , Phototherapy , SemiconductorsABSTRACT
Traditional photosensitizers (PSs) show reduced singlet oxygen (1 O2 ) production and quenched fluorescence upon aggregation in aqueous media, which greatly affect their efficiency in photodynamic therapy (PDT). Meanwhile, non-targeting PSs generally yield low efficiency in antibacterial performance due to their short lifetimes and small effective working radii. Herein, a water-dispersible membrane anchor (TBD-anchor) PS with aggregation-induced emission is designed and synthesized to generate 1 O2 on the bacterial membrane. TBD-anchor showed efficient antibacterial performance towards both Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). Over 99.8 % killing efficiency was obtained for methicillin-resistant S.â aureus (MRSA) when they were exposed to 0.8â µm of TBD-anchor at a low white light dose (25â mW cm-2 ) for 10 minutes. TBD-anchor thus shows great promise as an effective antimicrobial agent to combat the menace of multidrug-resistant bacteria.
Subject(s)
Drug Resistance, Multiple, Bacterial/drug effects , Microbial Sensitivity Tests/methods , Photosensitizing Agents/therapeutic use , Humans , Photosensitizing Agents/pharmacologyABSTRACT
We developed a biodegradable photothermal therapeutic (PTT) agent, π-conjugated oligomer nanoparticles (F8-PEG NPs), for highly efficient cancer theranostics. By exploiting an oligomer with excellent near-infrared (NIR) absorption, the nanoparticles show a high photothermal conversion efficiency (PCE) up to 82%, surpassing those of reported inorganic and organic PTT agents. In addition, the oligomer nanoparticles show excellent photostability and good biodegradability. The F8-PEG NPs are also demonstrated to have excellent biosafety and PTT efficacy both in vitro and in vivo. This contribution not only proposes a promising oligomer-based PTT agent but also provides insight into developing highly efficient nanomaterials for cancer theranostics.
Subject(s)
Nanoparticles/chemistry , Neoplasms/therapy , Phototherapy , Theranostic Nanomedicine , A549 Cells , Animals , Cell Line, Tumor , Cell Survival/drug effects , HeLa Cells , Humans , Mice , Nanoparticles/metabolism , Neoplasms/pathologyABSTRACT
Nanomaterial-mediated phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is an effective anticancer intervention that relies on light activation of photoactive nanomaterials localized in tumors. Recently, combinational PDT/PTT offered a practical pathway to relieve resistance of monotherapy, surmount undesirable side effects and provide a synergistic effect to enhance phototherapeutic efficiency. Herein, we report a facile strategy to integrate protoporphyrin IX (PpIX) into nanoscale metal-organic frameworks (NMOFs) and control their photoactive properties for combinational cancer PDT and PTT. With optimized PpIX conjugation, the as-fabricated nanoparticles (nPCU NPs) exhibit (1) improved dispersibility and particle stability, (2) simultaneous generation of reactive oxygen species and heat effectively through activation by a single-wavelength laser of 635 nm, and (3) maintenance of porosity for further application as drug delivery vehicles. Moreover, in vitro investigation of nPCU NPs demonstrates effective cellular uptake, successful endosomal escape and enhanced phototherapeutic efficacy under both normoxic and hypoxic conditions. Therefore, this study developed a novel type of phototherapeutic nanoplatform with optimal properties for applicable cancer phototherapy.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Carriers/chemistry , Metal Nanoparticles/chemistry , Metal-Organic Frameworks/chemistry , Photosensitizing Agents/pharmacology , Protoporphyrins/pharmacology , Antineoplastic Agents/radiation effects , Cell Line, Tumor , Doxorubicin/pharmacology , Drug Carriers/toxicity , Humans , Hyperthermia, Induced/methods , Light , Metal Nanoparticles/toxicity , Metal-Organic Frameworks/toxicity , Photochemotherapy/methods , Photosensitizing Agents/radiation effects , Proof of Concept Study , Protoporphyrins/radiation effects , Tumor Hypoxia/drug effectsABSTRACT
Development of high-performance photoactive agents with tumor-specific capability for effective nanotherapeutics has received much attention in the past decades. Herein, we report a nanotherapeutic based on bis-diketopyrrolopyrrole (BDPP) conjugated polymer nanoparticles (PBDPP NPs) with remarkable near-infrared (NIR) absorption at 808â¯nm and high photothermal energy conversion efficiency up to 60%. In particular, precise glioblastoma-specific capability and killing ability for glioblastoma cells were effectively achieved in vitro by treating with only PBDPP NPs to induce cell apoptosis or by interaction with PBDPP NPs under NIR laser irradiation to trigger cell necrosis. Impressively, a half-maximal inhibitory concentration as low as of â¼0.15⯵gâ¯mL-1 was achieved, and the magnitude is 5 to 4.4â¯×â¯104-fold lower than those of reported agents. In vivo experiment with mice further shows that the PBDPP NPs show good efficacy of photothermal therapy and complete tumor elimination using a record-low dosage of 0.35â¯mgâ¯mL-1 under 808â¯nm irradiation of low power (0.5â¯Wâ¯cm-2). This study thus demonstrates a promising strategy of low-dose, high-efficacy polymer-based nanoagonist for specific phototherapy of glioblastoma.