Quintuple-acceptor engineering of anti-quenching conjugated oligomers for highly efficient NIR-Ⅱb imaging and phototheranostics
Yuliang Yang , Jingyi Zhang , Yu Wang , Huan Chen , Yijian Gao , Xiliang Li , Yingpeng Wan , Qi Zhao , Ning Li , Shengliang Li
Precise near-infrared (NIR) theranostics desire to include diagnosis and therapy simultaneously and this has achieved great development, longing with the advances of material science in the last few years [1–10]. Phototheranostic agents can utilize NIR light excitation to induce reactive oxygen species (ROS) for photodynamic therapy (PDT) or local heat for photothermal therapy (PTT), with bioimaging functions such as fluorescence, photoacoustic signals, and magnetic resonance [11–22]. With the advantages of high precision and low invasiveness, many phototheranostic agents have developed rapidly in recent years [1,23,24]. Among these photoheranostics, fluorescence-assisted phototheranostic agents are more desirable because of their superior high resolution and real-time visualization [25,26]. However, the fluorescence-assisted phototheranostic agents have focused mainly on visible (400–700 nm) and first NIR (NIR-I, 700–1000 nm) fluorescence and thus have been applied only to superficial tissue imaging because of their limited tissue penetration [27,28]. Fluorescence bioimaging in the second NIR (NIR-Ⅱ, 1000–1700 nm) region, especially in the NIR-Ⅱb window (1500–1700 nm), can provide high-definition in vivo visualization of physiological activity and tissue microstructure at high speed, with negligible autofluorescence, reduced light scattering, and minimal photodamage [25,29,30]. Thus, a suitable agent for NIR-Ⅱ imaging holds great potential for high-performance phototheranostics in living organisms. However, these advances are severely restricted by the rarity of efficient NIR-Ⅱ responsive phototheranostic materials. Therefore, developing high-performance phototheranostic materials with good NIR-Ⅱ fluorescence is highly desirable but challenging.
Conjugated materials, characterized by typical electronic delocalization and conjugated effects in the backbone, have long been favoured by scientific researchers owing to their tuned structure, strong photoactivities, and high biocompatibility [19,31–34]. By molecular engineering, the photophysical properties of conjugated materials can be finely tuned and thus widely used for biomedical applications, including bioimaging, optical sensing, and disease treatment [27,35–37]. Recently, the NIR-Ⅱ fluorescence emission of conjugated materials was further explored, and good advances in bioimaging in vivo in the NIR-Ⅱ region were achieved [34,38,39]. However, NIR-Ⅱ emissive conjugated materials regularly encounter severe fluorescence quenching in biomedical applications because the nanoparticle (NP) encapsulation of conjugated materials induces molecular aggregation [40–42]. To overcome this issue, many strategies, such as additive agent doping of guest materials with large steric hindrance structures, have been developed to decrease fluorescence quenching for improved NIR-Ⅱ bioimaging [41,43–45]. These structures with large steric hindrance can effectively reduce intermolecular forces, thereby reducing fluorescence quenching caused by molecular aggregation. However, very little attention has been given to the anti-quenching design of conjugated materials at the molecular level [38,46,47].
To overcome the above problem, we report for the first time that NIR-Ⅱ emissive conjugated oligomers can be used to conveniently achieve anti-quenching performance via multi-acceptor engineering (Scheme 1). We developed a one-pot reaction to synthesize multi-acceptor conjugated oligomers (SU-1, SU-2, and SU-5) with donor-acceptor-donor (D-A-D) structure and explored the anti-quenching properties of these oligomers in aggregate. Owing to their good anti-quenching performance, water-dispersive NPs of SU-5 with quintuple acceptors were prepared, and their efficiency in NIR-Ⅱ emission, photothermal conversion, and photodynamic effects under 808 nm light excitation was demonstrated. With these advantages, SU-5 NPs achieve high-resolution NIR-Ⅱ whole-body angiography beyond 1500 nm with good distinguishability. Additionally, via dynamic NIR-Ⅱ monitoring for tumor targeting, SU-5 NPs exhibit relapse-free tumor photoablation upon 808 nm light irradiation with relatively high biosafety. Thus, this work provides an artful multi-acceptor engineering approach for developing anti-quenching theranostic materials with efficient cancer photoheranostics.
Previous studies have revealed that the coupling reaction between the donor (D) and acceptor (A) can yield D-A-, D-A-D-, AND A-D-A-type conjugated oligomers (Fig. 1A) [48–51]. In this work, a one-pot Stille coupling reaction was developed to synthesize multi-acceptor conjugated oligomers (SU-n. n = 1, 2, and 5) via molecular engineering (Fig. 1B and Fig. S1 in Supporting information). In SU-n, triphenylamine and benzo[1,2-c; 4,5-cʹ]bis[1,2,5]thiadiazole (BBT) were respectively performed as the D and A fragments, with a π-bridge thiophene. The chemical structures of three SU-n products, SU-1, SU-2, and SU-5, were well characterized and confirmed via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (Figs. S2–S8 in supporting information). To further understand the optical properties of SU-n, the lowest unoccupied molecular orbital (LUMO), highest occupied molecular orbital (HOMO), and geometries of SU-1, SU-2, and SU-5 were simulated via density functional theory (DFT) calculations. As shown in Fig. 1C, the LUMO electron clouds of three SU-n are concentrated in the acceptor part, whereas the HOMO electron clouds of these SU-n are uniformly dispersed in the acceptor and donor parts. As noted by DFT calculations, the energy gaps (Egs) of SU-1, SU-2, and SU-5 are calculated to be 1.06, 1.14, and 1.15 eV, respectively, indicating similar Eg levels. Furthermore, the optimal conformation geometry studies revealed that SU-2 and SU-5 have a large dihedral angle of ~55° between the BBT units and the whole molecule has a typical nonplanar appearance. This nonplanar structure will weaken the π-π-stacking force in the aggregate, thus reducing the intramolecular interaction and fluorescence quenching properties. This may be due to the N‒N charge repulsion between BBT and BBT. When dissolved in tetrahydrofuran (THF), SU-1, SU-2, and SU-5 had maximum absorption peaks at 900, 840, and 794 nm with the molar absorption coefficients of 11,792,45,432, and 27,311 L mol−1 cm−1, respectively (Fig. 1D and Fig. S9 in Supporting information). These typical NIR absorption peaks are produced by intramolecular electron transfer (ICT) between the donors and acceptors. Upon irradiation with an 808 nm laser, three molecules exhibited bright NIR-Ⅱ fluorescence emission ranging from 900 nm to 1500 nm (Fig. 1E). Electron spinning resonance (ESR) spectroscopy revealed the radical features of three molecules (Fig. S10 in Supporting information). Moreover, the change in the fluorescence emission of these SU-n during aggregation was investigated in THF with different water fractions. As shown in Fig. 1F and Fig. S11 (Supporting information), with increasing water fraction, all SU-n samples exhibited aggregation-induced quenching effects, especially at high water fractions of the THF/water mixture. However, among these SU-n samples, SU-5 has a relatively good anti-quenching ability. Notably, the fluorescence emission of SU-5 at a 95% water fraction increased nearly 150- and 2-fold over those of SU-1 and SU-2, respectively. The good anti-quenching performance of SU-5 may be derived from the large dihedral angle between BBT and BBT in the molecular skeleton, which appropriately prevents intermolecular stacking in an aggregated state. These results demonstrate that SU-5 has good anti-quenching NIR-Ⅱ performance and therefore holds good potential for further bioimaging and phototherapy in the NIR-Ⅱ window.
To investigate the potential biological applications of SU-5, water-dispersive NPs were produced via self-assembly with the amphiphilic block polymer 1, 2-distearoyl-sn–glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)−2000] (DSPE-PEG2000) via the classical nanoprecipitation method (Fig. 2A) [52]. The hydrate particle size of the SU-5 NPs was measured to be 74.3 nm and their polydispersity index (PDI) was 0.26 according to the dynamic light scattering method (Fig. 2B). The morphology and size of the SU-5 NPs were further confirmed via transmission electron microscopy (TEM), which revealed that the SU-5 NPs were approximately 60 nm of spherical morphology. A negative zeta potential of −44.8 mV was obtained for the SU-5 NPs, and the NPs achieved good stability even after 14 days of storage (Fig. 2C and Fig. S12 in supporting information). The absorption and emission spectra of the SU-5 NPs were subsequently characterized, and the results are shown in Fig. 2D. The maximal absorbance peak of the SU-5 NPs was located at 794 nm, and the absorbance at 808 nm was 99% of the maximal peak. When excited by an 808 nm laser, SU-5 NPs exhibited a maximal fluorescence peak at 1116 nm with a trailing of more than 1500 nm. As shown in Fig. 2E, the SU-5 NPs displayed bright and concentration-dependent NIR-Ⅱ fluorescence emission. The SU-5 NPs exhibited a NIR-Ⅱ fluorescence quantum yield of 0.045% using IR26 as a standard reference (Fig. S13 in Supporting information) [53]. As illustrated in Fig. 2F and Fig. S14 (Supporting information), the SU-5 NPs showed good photostability within 60 min irradiation of 808 nm laser (1 W/cm2), whereas the Food and Drug Administration (FDA)-approved indocyanine green (ICG) almost completely lost its absorbance and NIR-Ⅱ fluorescence under the same conditions, demonstrating the good photostability of the SU-5 NPs. The NIR-responsive performance of the SU-5 NPs aqueous solution was subsequently detected via laser irradiation at 808 nm. As presented in Fig. 2G and Fig. S15 (Supporting information), the temperature of the SU-5 NPs solutions quickly increased with an 808 nm laser (1.0 W/cm2) irradiation for 10 min. In contrast, the temperature of pure water hardly changed under the same conditions. In a reported approach, the SU-5 NPs have a photothermal conversion efficiency (PCE) of 43.0%, which is comparable to that of previously reported photothermal agents (PTAs) (Fig. 2H and Table S1 in Supporting information). The concentration-dependent and power-dependent effects were further demonstrated (Fig. 2I). Furthermore, the photothermal stability of the SU-5 NPs was also studied, and the results are shown in Figs. 2J and K. After six cycles of 1 W/cm2 laser irradiation at 808 nm, the highest temperature of ICG gradually decreased, after which the PTT performance decreased at the end of the six cycles of light irradiation. However, the PTT efficiency of the SU-5 NPs remained unchanged under the same conditions. Notably, the NIR absorption of the SU-5 NPs after light irradiation remained nearly the same as those after no treatment (Fig. 2L). In addition, the ROS production ability of SU-5 NPs was further explored via a total ROS sensor 2′, 7′-dichlorodihydrofluorescein diacetate (DCFH-DA). As illustrated in Fig. 2M and Fig. S16 (Supporting information), upon 10 min laser at 808 nm, the nonfluorescent DCFH-DA in the presence of SU-5 NPs was transformed into green fluorescent DCF, with a 9.0-fold increase in fluorescence. As a control, the fluorescence of the group without SU-5 NPs remained essentially unchanged. The results revealed that SU-5 NPs have sufficient ROS production under a laser excitation of 808 nm, suggesting the efficient PDT activity of the SU-5 NPs. As summarized in Fig. 2N, the SU-5 NPs simultaneously maintained the NIR-Ⅱ fluorescence signal, PTT effect, and PDT effect under 808 nm laser irradiation, demonstrating their versatile NIR activities for bioimaging and phototherapy.
To further explore the cell endocytosis of the SU-5 NPs, fluorescein isothiocyanate (FITC)-labelled SU-5 NPs were prepared via the coassembly of FITC-modified DSPE-PEG2000 (Fig. 3A). Flow cytometry was used to evaluate the uptake of the FITC-labelled SU-5 NPs by murine breast cancer 4T1 cells, and the results revealed that the SU-5 NPs efficiently entered the 4T1 cells via a time-related feature (Fig. 3B). To further reveal the intracellular distribution, cell colocalization analysis was performed via confocal microscopy. As illustrated in Fig. 3C and Fig. S17 (Supporting information), the green signal of the FITC-labelled SU-5 NPs overlapped well with the LysoTracker Red signal, resulting in a yellowish signal in the merged image, which indicates that the SU-5 NPs were located in the lysosome. The experimental results showed that SU-5 NPs were still stuck in lysosomes after long incubation. The in vitro antitumor activities of the SU-5 NPs were evaluated via a standard 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) assay, and the results are shown in Figs. 3D and E. Without laser irradiation, the SU-5 NPs exhibited negligible cytotoxicity toward 4T1 tumor cells and normal mouse fibroblast L929 cells. However, the viability of 4T1 cells gradually decreased in response to increasing concentrations of SU-5 NPs under 10 min irradiation of 808 nm laser (1 W/cm2). Notably, the survival rate of 4T1 cells was reduced to less than 10% at a dose of 75 µg/mL SU-5 NPs, demonstrating the good antitumor activity of the SU-5 NPs. To confirm the above results, live/dead cell staining was further performed on the cells after they were treated with SU-5 NPs and light excitation. As shown in Fig. 3F, almost all of the cells in the phosphate buffered saline (PBS), PBS with 808 nm laser irradiation (PBS+L), and SU-5 NPs (NPs) groups were stained with green calcein-AM, while those in the SU-5 NPs with 808 nm laser irradiation (NPs+L) group emitted red fluorescence from propidium iodide (PI), which demonstrated the efficiency of the SU-5 NPs against 4T1 cells. In addition, flow cytometry was also used to analyze the apoptosis of 4T1 cells after SU-5 NPs treatment (Fig. 3G). After SU-5 NPs treatment plus light irradiation, the 4T1 cells exhibited severe cell apoptosis, further indicating the potential antitumor mechanism of the SU-5 NPs.
Taking advantage of the anti-quenching fluorescence properties of the SU-5 NPs, the NIR-Ⅱ angiography performance of the SU-5 NPs was further investigated in a BALB/c mouse. The protocols of the animal experiments are approved by the Institutional Ethical Committee of Animal Experimentation of Soochow University. The mouse was intravenously injected with the SU-5 NPs (1 mg/mL, 100 µL) and then placed on the NIR-Ⅱ imaging system for further blood vessel visualization. As shown in Fig. 4A, the systemic blood vessels exhibited bright NIR-Ⅱ fluorescence after being injected with the SU-5 NPs immediately. Additionally, NIR-Ⅱ angiography of the whole body was achieved successfully after various long-pass (LP) filters from 900 nm to 1500 nm were applied, demonstrating good NIR-Ⅱb fluorescence bioimaging. Moreover, the signal-to-background ratio (SBR) and full width at half maximum (FWHM) of the images after various LP filters were quantitatively analyzed and are shown in Fig. 4B. Among these NIR-Ⅱ images, whole-body angiography after the 1400 nm LP filter exhibited the highest SBR, and labelled vessels in the 1400 nm LP filter have the lowest FWHM, indicating superior resolution of NIR-Ⅱ imaging at the 1400 nm LP filter. As previously reported, due to water's strong light absorption at ~1450 nm, the background generated by the diffused components is significantly suppressed, thus leading to higher SBR of 1400 nm LP than 1500 nm LP [30]. With this NIR-Ⅱ technology, we zoomed in on the local vessels of the mouse hindlimb for high-resolution angiography via stereo-lens imaging (Fig. 4C). The two adjacent blood vessels in the hindlimb were clearly distinguished under 1000, 1200, and 1400 nm LP filters, and the amplified image at the 1400 nm LP filter has an optimal SBR (Fig. 4D), highlighting the superior high-resolution NIR-Ⅱ angiography of SU-5 NPs under the 1400 nm LP filter. These results clearly demonstrate the high performance of SU-5 NPs in NIR-Ⅱ angiography, especially in the NIR-Ⅱb window.
Next, we applied to guide the PTT of the SU-5 NPs via NIR-Ⅱ fluorescence imaging. To image the in vivo drug delivery and tumor location, when the tumor volume arrived at ~50 mm3, 4T1 tumor-bearing mice were intravenously injected with SU-5 NPs (1 mg/mL, 100 µL), and real-time NIR-Ⅱ imaging was then performed at different postinjection times. As represented in Figs. 5A and B, NIR-Ⅱ fluorescence of the tumor continued to increase with increasing time of postinjection with a plateau after 24 h injection. Obvious NIR-Ⅱ fluorescence in the tumor site indicated the considerable tumor-targeting and retention abilities of the SU-5 NPs. In addition, 24 h postinjection was selected as the optimal time point for further PTT application. The in vivo PTT performance of SU-5 NPs was then investigated in 4T1 tumor-bearing nude mice. When the volume of the solid tumor reached ~50 mm3, the 16 mice were randomized into 4 groups: PBS, PBS with 808 nm laser irradiation (PBS+L), SU-5 NPs (NPs), and SU-5 NPs with 808 nm laser irradiation (NPs+L). For treatment, 100 µL of PBS or SU-5 NPs at a concentration of 1 mg/mL were treated in the mice via intravenous injection. For the PBS+L and NPs+L groups, 10 min irradiation of 808 nm laser (1 W/cm2) was performed at the tumor site after 24 h injection. During the irradiation process, the temperature variation of the tumor was recorded via an infrared thermal imager. During the irradiation process, the temperature variation of the tumor was recorded via an infrared thermal imager. As depicted in Figs. 5C and D, the tumors in the PBS, PBS+L, and NPs groups only showed slightly changed temperature after 10 min of exposure to the 808 nm laser. In contrast, the NPs+L group triggered a rapid temperature increase in the tumor location, with a relatively high temperature of 55 ℃ after 808 nm laser illumination for 6 min, which indicates that the SU-5 NPs can achieve good in vivo photothermal therapeutic performance. Volume monitoring of the tumors revealed that NPs+L almost completely suppressed tumor growth, whereas the other three groups had similar growth tendencies within 18 days of treatment (Fig. 5E and Fig. S18 in Supporting information). Notably, there was no obvious residual tumor or relapse after SU-5 NPs treatment (Figs. 5F and G). Additionally, the body weights of the treated mice did not significantly differ within 18 days of treatment (Fig. 5H). To further investigate the efficacy of SU-5 NPs treatment, tumor biopsies, including hematoxylin and eosin (H&E) staining and dUTP nick end labelling (TUNEL) detection were performed on tumor tissue harvested from the treated mice. As shown in Fig. 5I, among these groups, only the NPs+L group exhibited a high percentage of apoptotic tumor cells in the H&E and TUNEL tests, indicating that SU-5 NPs irradiation can induce apoptosis for antitumor treatment. These results confirmed that the high-performance PTT of SU-5 NPs can efficiently eliminate in vivo tumors with NIR-Ⅱ imaging guidance.
Taking advantage of the results of preliminary experiments in which the body weight was unchanged after 18 days of treatment, we further investigated the in vivo biocompatibility and biosafety of the SU-5 NPs. Thus, tissue biopsy of the main organs from the treated mice was performed via H&E staining at the end of 18 days of treatment. There were no significant changes in the morphological characteristics of the organs, under laser irradiation or SU-5 NPs treatment, indicating good biocompatibility of this treatment with organs (Fig. 6A). Moreover, whole blood and blood biochemical analyses of the treated mice were carried out, and the results demonstrated that the treatment SU-5 NPs with laser irradiation failed to produce noticeable changes in the indices of blood biochemistry, which demonstrated that the SU-5 NPs treated mice had no noticeable infection or inflammation in the body or side effects on liver or kidney functions (Fig. 6B). These investigations preliminarily demonstrated the good in vivo biocompatibility and biosafety of the SU-5 NPs within 18 days of treatment.
In summary, we developed multi-acceptor conjugated oligomers with anti-quenching properties and thus achieved highly efficient NIR-Ⅱb imaging and phototheranostics. With multi-acceptor engineering, multiacceptor conjugated oligomers were synthesized via a one-pot reaction method, which demonstrated that the quintuple-acceptor SU-5 has good anti-quenching properties in NIR-Ⅱ emission. After being encapsulated into the NPs, the SU-5 NPs showed bright NIR-Ⅱ emission and dual PTT and PDT phototherapy simultaneously. With these advantages, SU-5 NPs achieve high-resolution NIR-Ⅱ whole-body and local angiography even with emission beyond 1500 nm. Moreover, in vivo experiments proved that SU-5 NPs are good candidates for high-performance phototheranostic agents for NIR-Ⅱb imaging and cancer photoablation under 808 nm laser irradiation. The high biosafety of SU-5 NPs was also demonstrated. Thus, we anticipate that a multi-acceptor engineering strategy could pave the way for the development of high-performance phototheranostic agents, potentially boosting the promotion of NIR-Ⅱ bioimaging and phototherapy applications.
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Yuliang Yang: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology. Jingyi Zhang: Writing – review & editing, Visualization, Methodology. Yu Wang: Writing – review & editing, Visualization, Project administration, Methodology. Huan Chen: Writing – review & editing, Writing – original draft, Visualization, Methodology. Yijian Gao: Writing – review & editing, Visualization, Methodology. Xiliang Li: Writing – review & editing, Methodology. Yingpeng Wan: Writing – review & editing, Methodology. Qi Zhao: Writing – review & editing, Methodology. Ning Li: Writing – review & editing, Writing – original draft, Visualization, Project administration, Methodology. Shengliang Li: Writing – review & editing, Writing – original draft, Visualization, Supervision, Project administration, Methodology, Conceptualization.
This work was supported by the National Natural Science Foundation of China (Nos. 52173135, 22207024), the Natural Science Foundation of Jiangsu Province (No. BK20231523), Jiangsu Specially Appointed Professorship, Leading Talents of Innovation and Entrepreneurship of Gusu (No. ZXL2022496), and the Suzhou Science and Technology Program (No. SKY2022039). This work was also funded by the China Postdoctoral Science Foundation (Nos. 2022M712305, 2023M742536) and the Jiangsu Funding Program for Excellent Postdoctoral Talent (No. 2023ZB011). The authors would also like to acknowledge the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions and Suzhou International Joint Laboratory for Diagnosis and Treatment of Brain Diseases.
Supplementary material associated with this article can be found, in the online version, at doi:
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Scheme 1 Schematic illustration of anti-quenching conjugated oligomers for bioimaging and phototherapies of tumors. (A) One-pot synthesis and characteristics of multi-acceptor conjugated oligomers. (B) Preparation and photophysical activities of SU-5 NPs. (C) Multiple tumor phototheranostics of SU-5 NPs.
Figure 1 (A) Classical molecular synthesis of conjugated molecules. (B) Multiple acceptor molecular engineering strategy for D-(A)n-D molecules (SU-n. n = 1, 2, and 5). (C) Molecular structure and DFT calculations of the SU-1, SU-2, and SU5 molecules. (D, E) Optical characterizations of the SU-n molecules. (F) Anti-quenching performance of SU-n molecules in THF with different water fractions.
Figure 2 (A) Synthesis diagram of SU-5 NPs. (B) Size distribution and TEM image of the SU-5 NPs. Scale bar: 200 nm. (C) Size and PDI stability of SU-5 NPs within 14 days of storage. (D) Normalized optical characterization of the SU-5 NPs. (E) Concentration-dependent fluorescence performance of SU-5 NPs under 808 nm laser irradiation. (F) Fluorescence stabilities of SU-5 NPs and ICG at various illumination times. (G) Photothermal curves of SU-5 NPs at different concentrations. (H) Temperature profile of SU-5 NPs under illumination, and linear time data against –Ln(θ) during the cooling period. (I) Power-dependent photothermal curves of SU-5 NPs. (J) Photothermal stabilities of SU-5 NPs and ICG within six cycles. (K) Thermal photographs of the SU-5 NPs during the photothermal stability experiment. (L) Absorbance Changes of the SU-5 NPs before and after irradiation. (M) Plots of the relative fluorescence changes in DCFH after treatment with or without SU-5 NPs under 808 nm laser irradiation. (N) Schematic illustration of the versatile NIR activities of SU-5 NPs upon 808 nm excitation.
Figure 3 (A) Diagram of FITC-labelled SU-5 NPs. (B) Flow cytometry plot of FITC-labelled SU-5 NPs uptake by 4T1 cells. (C) Colocalization images of FITC-labelled SU-5 NPs in 4T1 cells. DAPI, 4′, 6-diamidino-2-phenylindole. (D) Cell viability of 4T1 cells after being treated with SU-5 NPs at various concentrations with or without light irradiation. (E) Cell viability of L929 cells after being treated with SU-5 NPs at various concentrations. (F) Confocal images of live/dead staining in SU-5 NPs treated 4T1 cells. (G) Flow cytometry plot of the apoptosis of 4T1 cells after various treatments. ns: not significant. Data are presented as mean ± standard deviation (SD) (n = 3). P < 0.05, ****P < 0.0001.
Figure 4 (A) In vivo NIR-Ⅱ imaging of the whole body using SU-5 NPs after various LP filters. (B) Corresponding SBR and FMWH analyses of the tissue labelled with the blue line in (A). (C) High-resolution NIR-Ⅱ imaging of SU-5 NPs-labelled hindlimb blood vessels after various LP filters. (D) Corresponding SBR analyses of the tissue labelled with the blue line in (C). All the samples were excited by an 808 nm laser.
Figure 5 (A) Tumor targeted images of SU-5 NPs -treated mice at different postinjections via NIR-Ⅱ imaging. (B) Quantitative analysis of the NIR-Ⅱ fluorescence signal in the tumors. (C) Thermal photographs of the treated mice within an 808 nm laser irradiation (1 W/cm2) for 10 min. (D) Corresponding temperature profiles of the tumors from the treated mice. (E) Tumor growth curves of the treated mice within 18 days of treatment. (F) Digital tumor images from the treated mice after various treatments. (G) Tumor weights of the treated mice after 18 days of treatment. (H) Body weight analysis of the mice with different treatments. (I) Various biopsies of the tumor from the mice with different treatments. Data are presented as mean ± SD (n = 4). ***P < 0.001, ****P < 0.0001.
Figure 6 (A) Tissue biopsy of the main organs from different groups by H&E staining. (B) Complete blood test and biochemistry analysis of the treated mice after 18 days of treatment. RBC, red blood cell; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; HGB, hemoglobin; PCT, plateletcrit; MPV, mean platelet volume; Gran, granulocyte; CREA, creatinine; PDW, platelet distribution width; HCT, hemocytotripsis; MCH, mean corpuscular hemoglobin; RDW, red blood cell distribution width; AST, aspartate aminotransferase; UREA, urea. Data are presented as mean ± SD (n = 3).
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