RESUMO
Photothermal therapy (PTT) has attracted attention as a highly effective non-invasive treatment method. However, the high localized temperatures (>50 °C) required for its treatment will inevitably cause damage to the surrounding normal tissues. Therefore, it is important to develop novel and effective strategies to achieve mild photothermal therapy (mPTT). The overexpression of heat shock proteins (HSPs), a widespread heat stress protein, leads to the generation of heat resistance in cancer cells, which seriously affects the therapeutic effect. Thus, inhibiting the expression of HSPs to reduce the heat resistance of tumor cells is expected to enhance the therapeutic effect of mPTT. Here, we successfully synthesized a fluorescent probe bonded with an amphiphilic polypeptide to a cyanine dye and achieved physical encapsulation of the blocker SB705498 through a self-assembly process. SB705498 promotes transient receptor potential vanilloid member 1 (TRPV1) channel blockade that can inhibit the translocation of the heat shock transcription factor 1 (HSF 1) by blocking the influx of calcium and thus affecting the expression of HSPs, which has the potential to enhance the thermotherapy of cancer under mild conditions. In addition, the nanoparticles enabled NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10â¯%). Therefore, this study provides a new strategy for realizing precise mPTT(<45 °C) guided by NIR-II imaging. STATEMENT OF SIGNIFICANCE: Inhibition of overexpression of heat shock proteins (HSPs) in cancer photothermal therapy (PTT) is expected to enhance the therapeutic effect of mild photothermal therapy (mPTT). In this study, we synthesized a fluorescent probe bonded to cyanine dyes with amphiphilic polypeptides and physically wrapped the blocker SB705498 through a self-assembly process. As a transient receptor potential vanillin 1 (TRPV1) channel blocker, SB705498 inhibits heat shock transcription factor 1 (HSF1) translocation by blocking calcium ion influx, thereby improving mPTT efficacy by inhibiting the expression of HSPs. The nanoparticles also enable NIR-II fluorescence imaging with good stability and high photothermal conversion efficiency (48.10â¯%). Thus, this study provides a new strategy for NIR-II mPTT.
Assuntos
Raios Infravermelhos , Nanopartículas , Peptídeos , Terapia Fototérmica , Canais de Cátion TRPV , Nanopartículas/química , Canais de Cátion TRPV/metabolismo , Humanos , Peptídeos/química , Peptídeos/farmacologia , Nanomedicina Teranóstica/métodos , Animais , Corantes Fluorescentes/química , Fatores de Transcrição de Choque Térmico/metabolismo , Linhagem Celular Tumoral , Camundongos , Camundongos NusRESUMO
The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG2000-P(Asp)10), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo.
RESUMO
Stable organic radicals have emerged as a promising option to enhance fluorescence quantum yield (QY), gaining traction in medical treatment due to their unique electronic transitions from the ground state (D0) to the doublet excited state (D1). We synthesized a stable dicyanomethyl radical with a NIR-II fluorescence QY of 0.86 %, surpassing many NIR-II organic dyes. Subsequently, amphiphilic polymer-encapsulated nanoparticles (NPs) containing the radical were created, achieving a NIR-II fluorescence QY of 0.32 %, facilitating high-contrast bio-imaging. These CNPPs exhibit self-enhanced photothermal properties, elevating photothermal conversion efficiency (PCE) from 43.5 % to 57.5 % under 915 nm laser irradiation. This advancement enables more efficient photothermal therapy (PTT) with lower dye concentrations and reduced laser power, enhancing both feasibility and safety. Through regular fractionated mild photothermal therapy, we observed the release of damage-associated molecular patterns (DAMPs) and an increase in cytokine expression, culminating in combined mild phototherapy (m-PTT)-mediated immunogenic cell death (ICD). Consequently, we developed an immunostimulatory tumor vaccine, showcasing a novel approach for refining photothermal agents (PTA) and optimizing the PTT process.
Assuntos
Raios Infravermelhos , Nanopartículas , Peptídeos , Nanopartículas/química , Peptídeos/química , Peptídeos/farmacologia , Animais , Humanos , Camundongos , Nanomedicina Teranóstica , Tamanho da Partícula , Terapia Fototérmica , Fototerapia , Radicais Livres/química , Propriedades de Superfície , Sobrevivência Celular/efeitos dos fármacosRESUMO
Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down-regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2-deoxy-D-glucose (2DG) is an anti-glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low-temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx-BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as-prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR-I/II fluorescence imaging-guided starvation/MPTT/PDT synergy therapy for tumors.
RESUMO
NIR-IIa fluorescence imaging (FI) and NIR-II photothermal therapy (PTT) have gained popularity due to the advantages of high temporal and spatial resolution and deep penetration. However, the hyperthermia (>48 °C) of conventional PTT with nonspecific warming and thermal diffusion may inevitably cause damage to healthy tissues or organs surrounding the tumor. Therefore, it is highly desirable to provide effective cancer treatment by implementing mild photothermal therapy (mPTT) at mild temperatures with lower laser power density. Here, the nanotheranostic platform FN@P-GA NPs with NIR-II absorption and NIR-IIa emission was developed by constructing J-aggregates. FN@P-GA possesses good biocompatibility, favorable NIR-IIa FI performance, decent stability, and high photothermal conversion efficiency (57.6 %), which lays a solid foundation for FI-guided mPTT. Due to its ability to effectively down-regulate the expression of HSP90 and reduce cellular thermoresistance to kill cancer cells, FN@P-GA successfully achieved NIR-IIa FI-guided mPTT and demonstrated its potent anti-tumor effect under 1064 nm laser irradiation at mild temperature and low power density (0.3 W/cm2).
Assuntos
Carbocianinas , Corantes Fluorescentes , Raios Infravermelhos , Terapia Fototérmica , Humanos , Carbocianinas/química , Carbocianinas/farmacologia , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Animais , Camundongos , Imagem Óptica , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula , Antineoplásicos/química , Antineoplásicos/farmacologia , Propriedades de Superfície , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Nanopartículas/química , Fluorescência , Linhagem Celular TumoralRESUMO
Correction for 'In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics' by Huiping Dang et al., J. Mater. Chem. B, 2022, 10, 5279-5290, https://doi.org/10.1039/D2TB00705C.
RESUMO
Thanks to deep penetration and high resolution, the second near-infrared window (NIR-II, 1000-1700 nm) fluorescence (FL) imaging is expected to gain favor in clinical applications, including macroscopic imaging for cancer diagnosis and microangiography for vascular-related disease diagnosis. Nevertheless, most NIR-II fluorescent probes, especially cyanine, are highly susceptible to self-quenching in the aggregated state, which severely limits their application in bioimaging. Here, the Br-modified cyanine dye F4 -Br and the amphiphilic polypeptide poly(oligo[ethylene glycol]methacrylate)-b-poly(benzyl-L-aspartic acid) (POEGMA-PBLA) are synthesized. By modulating the self-assembly of F4 -Br and POEGMA-PBLA to effectively inhibit the H-aggregation of F4 -Br in aqueous solutions, nanoprobe F4 -Br@P17 with outstanding antiquenching capability is developed. This prominent feature allows it to perform vascular microscopic imaging with high spatiotemporal resolution and assess hemodynamic characteristics. F4 -Br@P17 nanoparticles (NPs) with good stability and satisfactory biocompatibility also enable high contrast brightness for NIR-II FL imaging of tumors. Given the efficient enrichment at tumor sites and the promising photothermal conversion efficiency (43.5%), F4 -Br@P17 NPs successfully conduct photothermal therapy and exhibit superior antitumor efficiency under 1064 nm laser irradiation. These remarkable performances reveal the tremendous possibility of F4 -Br@P17 NPs for in vivo microscopic imaging and FL imaging-guided photothermal therapy in the NIR-II region.
Assuntos
Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Polietilenoglicóis , Imagem Óptica , Peptídeos , Linhagem Celular Tumoral , FototerapiaRESUMO
The conversion of lignocellulose into valuable chemicals has been recognized as the key technology in green chemistry. However, selective degradation of hemicellulose and cellulose with the production of lignin is still a challenge. Therefore, a two-step process has been developed to degrade corncob into xylose and glucose under mild conditions. At first, the corncob was treated with the lower concentration of zinc chloride aqueous solution (30-55 w%) at 95 °C with a short reaction time (8-12 min) and 30.4 w% (selectivity = 89%) of xylose obtained with a solid residue of the composite of cellulose and lignin. Next, the solid residue was treated with a high concentration of zinc chloride aqueous solution (65-85 w%) at 95 °C for about 10 min, and 29.4 w% (selectivity = 92%) of glucose can be obtained. Combining the two steps, the total yield of xylose is 97%, while glucose is 95%. In addition, high pure lignin can be obtained simultaneously, which was confirmed using HSQC studies. Furthermore, for the solid residue of the first-step reaction, a ternary deep eutectic solvent (DES) (choline chloride/oxalic acid/1,4-butanediol, ChCl/OA/BD) has been used to separate the cellulose and lignin efficiently, and high-quality cellulose (Re-C) and lignin (Re-L) were obtained. Furthermore, it provides a simple method to disassemble the lignocellulose for monosaccharides, lignin, and cellulose.
Assuntos
Glucose , Lignina , Lignina/química , Glucose/metabolismo , Xilose/química , Biomassa , Celulose/química , Solventes/química , HidróliseRESUMO
The second near-infrared IIa window (NIR-IIa, 1300nmâ¼1400nm) enables high-resolution imaging and deep-tissue tumor treatment due to its unique low tissue scattering and autofluorescence, high temporal-spatial resolution, and deep tissue penetration. Therefore, NIR-IIa fluorescence imaging-guided phototherapy is of specific interest. However, organic dyes and their nanoparticles for NIR-IIa phototheranostics are still scarce. Here, we have synthesized a Br- and piperazine-modified cyanine dye (FN) and its nanomicelles encapsulated by an amphiphilic polypeptide with sidechains of tertiary amine (PEA). The J-aggregates of P@FN9 with 1116 nm absorption and efficient NIR-IIa fluorescence emission were formed by the self-assembly of FN and PEA. P@FN9 nanoparticles (NPs) showed good stability and high photothermal conversion efficiency (55.4%). In addition, the high spatial resolution and signal-to-background ratio (SBR) of P@FN9 were demonstrated by NIR-IIa fluorescence imaging of mouse vasculature. The P@FN9 NPs successfully performed the NIR-IIa fluorescence imaging-guided photothermal therapy, and both in vitro and in vivo experiments indicated that the P@FN9 NPs exhibited effective antitumor effects under the NIR-II (1064 nm) laser irradiation. STATEMENT OF SIGNIFICANCE.
Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Piperazina , Fototerapia , Imagem Óptica , Nanopartículas/uso terapêutico , Corantes , Neoplasias/terapia , Peptídeos/farmacologia , Linhagem Celular TumoralRESUMO
For photothermal therapy (PTT), the improved targeting can decrease the dosage and promote the therapeutic function of photothermal agents, which would effectively improve the antitumor effect. The tumor microenvironment (TME) and cells are targets in designing intelligent and responsive theranostics. However, most of these schemes have been limited to the traditional visible and first near-infrared (NIR-I) regions, eager to expand to the second near-infrared (NIR-II) window. We designed and synthesized a polyethylene glycol conjugated and disulfide-modified macromolecule fluorophore (MPSS). MPSS could self-assemble into core-shell micelles in an aqueous solution (MPSS-NPS), while the small molecule probes were in a high aggregation arrangement inside the nanoparticle. The pronounced aggregation quenching (ACQ) effect caused them to the "sleeping" state. After entering the tumor cells, the disulfide bonds in MPSS-NPS broke in response to a high concentration of glutathione (GSH) in TME, and the molecule probes were released. The highly aggregated state was effectively alleviated, resulting in distinct absorption enhancement in the near-infrared region. Therefore, the fluorescence signal was recovered, and the photothermal performance was triggered. In vitro and in vivo studies reveal that the Nano-system is efficient for the smart NIR-II fluorescence imaging-guided PTT, even at a low dosage and density of irradiation.
Assuntos
Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Dissulfetos , Corantes Fluorescentes/química , Glutationa , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia , Nanomedicina Teranóstica/métodos , Microambiente TumoralRESUMO
Through the activation of packing arrangements of dyes to modulate their photophysical and/or photochemical properties, not only new NIR-II dyes but tumor-specific NIR-II imaging and therapy can also be achieved. Herein, we designed an acid-responsive polypeptide nanoparticle (P-ipr@Gal) encapsulated with a pH-sensitive amphiphilic polypeptide (P-ipr) as a carrier for the galactose-conjugated BODIPY (Gal-BDP) dye. When P-ipr@Gal NPs are enriched in tumor regions by the EPR effect, the acidic microenvironment (pH 6.4-6.8) promotes the disintegration of P-ipr@Gal nanomicelles and the release of sufficient Gal-BDP. The protonation of the julolidine nitrogen of the Gal-BDP dye switched on the molecular stacking transformation from the H-aggregate to J-aggregate. The J-aggregate significantly enhanced the redshift absorption and emission intensity, which enhanced the fluorescence brightness and photothermal therapeutic effect in the tumor region. We also prepared J-aggregates PAsp@Gal with non-acidic responsive polyaspartic acid benzyl esters (PAsp) encapsulated Gal-BDP, which remained "always-on" with J-aggregate characteristics. The P-ipr@Gal (or PAsp@Gal) J-aggregate has a maximum emission peak redshifted to nearly 1064 nm, with a 3.5-fold increase in the emission intensity compared to the H-aggregate at pH 7.4. Based on the effective accumulation of tumor sites and considerable PCE (>40%), P-ipr@Gal nanoparticles have a lower background and higher tumor background ratio, which makes them a potential NIR-II imaging-guided photothermal therapy agents.
Assuntos
Nanopartículas , Neoplasias , Compostos de Boro , Corantes , Galactose , Humanos , Nanopartículas/química , Peptídeos , Microambiente TumoralRESUMO
A novel NIR-II small-molecule D-A type organic fluorophore conjugation of triphenylamine, thiophene, and benzo[c,d] indol groups (TPA-Et) with strong electron-donating and accepting groups has been synthesized. The dye shows a significant Stokes shift for efficient fluorescence in the NIR-II region and high photothermal performance. The TPA-Et was then encapsulated by an amphiphilic copolymer P(OEGMA)20-P(Asp)14, and micelles (P@TP) has been prepared with outstanding NIR-II imaging performance, excellent photothermal conversion efficiency (52.5%) under 808 nm laser irradiation, and good photostability. Fluorescence imaging experiments have consistently shown that P@TP can image tiny blood vessels in mice, enrich effectively in the tumor region, and maintain a relatively stable NIR-II fluorescence signal in the tumor area for a long time up to 60 h. In vivo photothermal therapy has a highly significant anticancer effect without tumor recurrence, demonstrating the apparent advantages of P@TP as a NIR nanotheranostic platform in NIR-II imaging-guided photothermal therapy.
Assuntos
Nanopartículas , Neoplasias , Animais , Elétrons , Corantes Fluorescentes/química , Camundongos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Peptídeos , Fototerapia , Nanomedicina Teranóstica/métodosRESUMO
Achieving J-aggregation of a molecule is a fascinating way to construct fluorescent imaging and photothermal therapy agents in the second near-infrared window. Modulation of the balance between intermolecular π-π stacking and steric interactions is an elegant method to acquire J-aggregation dyes. Herein, we succeeded in synthesizing an aza-BODIPY dye with J-aggregation characteristics by introducing steric hindrance (TPA) and a π-bridge (thiophene) in the aza-BODIPY skeleton. In aqueous solutions, supramolecular J-aggregates with a regular lamellar stacking structure could quickly be formed by the dye-templated self-assembly and longer absorption (λmax = 939 nm) and emission (λmax = 1039 nm) bands were observed. After co-assembly of the dye and an amphiphilic polypeptide (POEGMA23-PAsp20), the obtained J-aggregation nanoparticles (J-NPs) with good water solubility and smaller size were more suitable for application in living organisms. In addition, the J-NPs exhibited good stability, considerable photothermal conversion capacity (η = 35.6%), and excellent resistance to pH, H2O2, and photobleaching. In vitro and in vivo experiments revealed that the J-NPs show great NIR-II fluorescence imaging capabilities and anti-tumor effects under 915 nm irradiation (1 W cm-2). This is a rare example of using BODIPY dyes to perform NIR-II fluorescence imaging-guided photothermal therapy under NIR-II irradiation.
Assuntos
Peróxido de Hidrogênio , Terapia Fototérmica , Compostos de Boro , Corantes , Imagem ÓpticaRESUMO
The rapidly growing demand for batteries has led to a lack of global mineral resources and rechargeable organic batteries are paid extensive attention, owing to the abundance resources, light weight, and high flexibility of organic electrodes. However, most organic electrodes that use aliphatic backbones are nondegradable, leading to unsustainability when active sites fail. In this study, a poly(aspartic acid) polypeptide (PASP) with amide links in the backbone and nitroxide radical pendant groups in the side chains is synthesized by modifying the polypeptides with 4-amino-2,2,6,6-tetramethylpiperidine. In combination with a Zn anode, the PASP-TEMPO composite electrode exhibits rapid charge-discharge and superior cycling stability with reversible two-electron redox reaction in aqueous electrolyte. The Zn/PASP-TEMPO organic radical battery delivers a discharge capacity of around 80â mAh g-1 by two-electron reaction and charge-discharge rates of up to 18â A g-1 . Because the redox reaction process of the nitroxyl radical turning into oxoammonium follows a p-type mechanism that interacts with an anion, three electrolytes with different anions are tested in the Zn/PASP-TEMPO organic radical battery. Experimental results indicate that discharge plateau voltage is tunable by choosing different zinc salts as electrolytes. Capacity retention of up to 97.4 % after 500â cycles is realized in 1â m ZnClO4 electrolyte, which can be attributed to the adjacent reaction potentials of the two-step one-electron reaction.
Assuntos
Eletrólitos , Elétrons , Eletrodos , Eletrólitos/química , Peptídeos , Água/química , ZincoRESUMO
It is essential to develop novel multifunctional and easily synthesized stable NIR-II fluorescent probes to guide photothermal therapy for tumors. Here, we propose a new strategy to construct boron dipyrromethene (BODIPY) J-aggregates by intermolecular hydrogen bonding (H-bond) and π-π stacking interactions to achieve fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm). A novel meso-benzamide galactose hexanoate-BODIPY (Gal-OH-BDP) amphiphilic small molecular dye was synthesized and it formed nanoparticles spontaneously in aqueous solution with a maximum emission wavelength near 1060 nm, which works as a smart nanomedicine for targeting NIR-II imaging-guided photothermal therapy (PTT) of hepatocellular carcinoma. Galactose not only provided hydrogen bonds to regulate the aggregation pattern of the molecules but also effectively targeted hepatocellular carcinoma cells and promoted the formation of well-dispersed nanoparticles of dye molecules due to their hydrophilicity. Moreover, due to high photothermal conversion efficiency (PCE = 55%), Gal-OH-BDP NPs achieve galactose-targeted NIR-II imaging and PTT, which is important for the precise diagnosis and treatment of tumors (Scheme 1). In the present research work, H-bond was introduced for the first time into BODIPY for building J-aggregates to achieve the NIR-II fluorescence.
Assuntos
Boro , Nanopartículas , Linhagem Celular Tumoral , Fluorescência , Galactose , Ligação de Hidrogênio , Fototerapia , Terapia Fototérmica , Porfobilinogênio/análogos & derivadosRESUMO
Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise for in vivo imaging and imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. It is very appealing to obtain NIR-II fluorescent probes through simple procedures and economical substrates. Herein, we developed a D-A-D' structure NIR-II photosensitizer (triphenylamine modified aza-Bodipy, TAB) based on the strong electron-withdrawing nature of borane difluoride azadipyrromethene's center (aza-BODIPY). Subsequently, halogen atoms (Br, I) were introduced to the TAB molecule, and TAB-2Br and TAB-2I were synthesized. Compared to the TAB molecule, a significant redshift in the emission wavelength, ultra-large Stokes shift (>300 nm), and enhanced singlet oxygen production capacity were acquired for the halogenated molecules. After self-assembly of TABs and an amphiphilic polypeptide POEGMA23-PAsp20, the obtained P-TAB, P-TAB-2Br, and P-TAB-2I nanoparticles exhibited excellent water solubility and biocompatibility, remarkable photothermal conversion efficiency (beyond 40%), and good resistance to photobleaching, heat, and H2O2. Under 808 nm laser irradiation, the P-TAB-2I exhibited an efficient photothermal effect and ROS generation in vitro. And in vivo experiments revealed that P-TAB-2I displayed efficient NIR-II fluorescence imaging and remarkable tumor ablation results. All of these results make TAB-2I potential organic probes for clinical NIR-II fluorescence imaging and cancer phototherapy.
Assuntos
Peróxido de Hidrogênio , Nanopartículas , Compostos de Boro , Linhagem Celular Tumoral , Nanopartículas/química , FototerapiaRESUMO
Most NIR-II fluorescent dyes, especially polymethine cyanine, face the inevitable self-quenching phenomenon in an aqueous solution. This unacceptable property has severely limited their application in high-resolution biological imaging. Here, a NIR-II macromolecular probe (MPAE) is synthesized through the structure modification of molecule probe and the covalent coupling of an amphiphilic polypeptide, which presents considerable biocompatibility and negligible systemic side effect. The molecule probe's stereo structure and the polymer's conjugation could effectively prevent the π-π stacking, thereby exhibiting excellent quenching resistance in aqueous solutions (absolute QY = 0.178%). This remarkable feature endows it with deeper tissue penetration than the clinically used indocyanine green (ICG) and high contrast brightness at the tumor site for the NIR-II fluorescence imaging. Based on the effective accumulation of tumor sites and considerable photothermal conversion efficiency (40.07%), the MPAE-NPS presents superior antitumor efficiency on breast tumor-bearing mice under the 1064 nm irradiation without rebound or recurrence. All these outstanding performances reveal the great promise of MPAE-NPS in Nano-drug delivery and imaging-assisted photothermal therapy in the NIR-II window.
Assuntos
Nanopartículas , Terapia Fototérmica , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes , Verde de Indocianina , Camundongos , Imagem Óptica , FototerapiaRESUMO
To achieve accurate fluorescence imaging-guided cancer therapy, intelligent systems with specific responsiveness to the tumor microenvironment need to be designed. Here, we have achieved both enhanced NIR fluorescence and photodynamic therapy by introducing a dimethylamino functional group in BODIPY dyes, which can be used as a pH sensor under acidic conditions by coordinating with the proton. At pH 7.4, the fluorescence is quenched due to the photo-induced electron transfer (PET) process. After the photosensitizer is protonated in tumor cell lysosomes (pH 4.0-5.5), the PET process is inhibited and the fluorophore emission capacity is restored (fluorescence enhancement up to 10-fold), resulting in near-infrared fluorescence with the OFF/ON transition inside the tumor and enhanced singlet oxygen production for lysosome targeting capability. Due to the substitution of heavy atom iodine, the compound has a high singlet oxygen quantum yield of 81.8% in dichloromethane. In addition, using a pH-sensitive amphiphilic polypeptide (POEGMA23-PE9) as a carrier to wrap the photosensitizer BDPI can release enough drug in the acidic environment (pH 5.5-6.5) of intracellular endosomes/lysosomes, which is conducive to more adequate interactions of the photosensitizer with H+ and more effective enhancement of fluorescence emission and 1O2 production, achieving precise fluorescence imaging capability and extremely low background toxicity.
Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Fluorescência , Nanopartículas/química , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/química , Cápsulas/química , Proliferação de Células/efeitos dos fármacos , Dimetilaminas/química , Dimetilaminas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Lisossomos/metabolismo , Camundongos , Peptídeos/síntese química , Peptídeos/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Células Tumorais CultivadasRESUMO
Due to the hydrophobicity of the cyanine dye and the huge conjugated plane, the cyanine dye is prone to H-aggregation in aqueous solution, and the ultraviolet absorption is blue-shifted. Here, a hydrophilic quaternary stereo-specific cyanine (HQS-Cy) dye has been synthesized and polypeptide based nanoparticles have been prepared, which improve the water solubility of the cyanine in two aspects. First, at the molecular level, the sulfonic acid group increases the water solubility of the dye molecule while the dimethyl-ammonium functional group repels the molecule through the charge-charge interaction, destroying the planar characteristics of the cyanine structure, increasing the molecular distance between the dye molecules, and preventing the accumulation of cyanine. Secondly, at the nano-micelle level, the use of amphiphilic polypeptide blocks to encapsulate the dye increases the water solubility of the dye while also increasing its biocompatibility. The HQS-Cy@P NPs prepared by the above methods exhibit the maximum absorption at 985 nm and maximum fluorescence emission at 1050 nm in aqueous solution. HQS-Cy@P exhibits good photothermal stability and significant photothermal conversion efficiency of about 35.5%, and both in vitro and in vivo studies revealed that it is an efficient system for NIR-II imaging-guided photothermal therapy of cancer.
Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carbocianinas/farmacologia , Corantes/farmacologia , Terapia Fototérmica , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/diagnóstico por imagem , Carbocianinas/síntese química , Carbocianinas/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Raios Infravermelhos , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Imagem Óptica , Solubilidade , Neoplasias do Colo do Útero/diagnóstico por imagemRESUMO
NIR-II fluorescence imaging-guided photothermal therapy is a potential tumor therapeutic that has exhibited accurate diagnosis and noninvasive therapy of tumors. Here, we developed an organic macromolecular nanoparticle (PFD) by encapsulating a fluorophore with an amphiphilic polypeptide. The PFD nanoparticle presented a uniform size of 70 nm with a slightly negative charge and exhibited superior photothermal conversion efficiency (40.69%), thermal imaging ability, and considerable photothermal stability. The PFD nanoparticle could accumulate at the tumor site by an enhanced penetration and retention effect and exhibited satisfactory fluorescence imaging and prominent photothermal inhibition effect. In vivo experiments demonstrated that PFD nanoparticles exhibited a prominent photothermal inhibition effect against the tumor. Meanwhile, the therapeutic procedure was monitored by both NIR-II fluorescence and infrared thermal imaging, which demonstrated that the PFD nanoparticles have a potential application in imaging-guided photothermal therapy of tumors.