Cancer including lung cancer, rectal and prostate cancer, colon cancer and breast cancer remains the leading cause of morbidity and mortality worldwide. The use of noninvasive imaging technique to detect cancers at an early stage and achieve imageguided cancer therapy provides better opportunities for patients to obtain effective treatment with fewer side effects. To date, photoacoustic (PA) imaging (PAI) is the fastest-growing area of biomedical imaging technology because PAI enables anatomical, functional and metabolic imaging of tumors with high resolution, high contrast and satisfactory penetration depth. However, the sensitivity of PAI to visualize tumors is determined by its endogenous contrast. By contrast, multifunctional nanoprobes have exhibited their potentials as theranostic agents for PAI-guided cancer theranostics.

Photoacoustic imaging (PAI) is a hybrid imaging method based on photoacoustic (PA) effects, which is able to capture the structure, function, and molecular information of biological tissues with high resolution. To date, therapeutic techniques under the guidance of PAI have provided new strategies for accurate diagnosis and precise treatment of tumors. In particular, conjugated polymer nanoparticles have been extensively inspected for PA-based cancer theranostics largely due to their superior optical properties such as tunable spectrum and large absorption coe±cient and their good biocompatibility, and abundant functional groups. This mini-review mainly focuses on the recent advances toward the development of novel conjugated polymer nanoparticles for PA-based multimodal imaging and cancer photothermal therapy.

Detection and visualization of β-galactosidase (β-gal) is essential to reflect its physiological and pathological effects on human health and disease, but it is still challenging to precisely track β-gal in vivo owing to the limitation of current analytical methods. In our work, we reported a photoacoustic (PA) nanoprobe for selective imaging of the endogenous β-gal in vivo. Our nanoprobe Cy7-β-gal-LP was constructed by encapsulation of a near-infra red (NIR) dye Cy7-β-gal within a liposome (LP, DSPE-PEG2000-COOH). The dye Cy7-β-gal was synthesized based on a dye Cy-OH where the hydroxyl group was replaced by a β-D-galactopyranoside residue, which can be recognized by β-gal as an enzyme hydrolytic site. With the addition of β-gal, the absorbance of Cy7-β-gal exhibited a significant red shift with the absorption peak moved from 600 nm to 680 nm, which should generate a switch-on PA signal at 680 nm in the presence of β-gal. In addition, as the fluorescence of the dye was totally quenched due to aggregation within the liposome, Cy7-β-gal-LP exhibited high PA conversion e±ciency. With the nanoprobe, we achieved the selective PA detection and imaging of β-gal in the tumor-bearing mice.

To improve the e±cacy of traditional chemotherapy and radiotherapy and reduce their serious side effects, further efforts need to be exerted to identify better cancer therapeutic options that are effective, affordable, and acceptable to patients. In this study, a novel theranostic agent was produced to perform synergetic cancer immunotherapy and phototherapy. The theranostic agent, named natural killer (NK) cells carrying indocyanine green loaded liposomes was synthesized NK cells with ICG nanoparticles to serve as the agent for a newly-established cancer treatment. It is expected that the developed synergistic therapy can pave a new avenue for improved e±cacy of cancer theranostics.

The photosensitizer (PS) as photodynamic therapy (PDT) agent, can also serve as the contrast agent for dual-modal fluorescence imaging (FLI) and photoacoustic imaging (PAI) for precise cancer theranostics. In this study, the PAI capability of commercial PS, benzoporphyrin derivative monoacid ring-A (BPD) were examined and compared with that from the other PSs and dyes such as TPPS4, Cy5 dye and ICG. We discovered that BPD exhibited its advantage as contrast agent for PAI. Meanwhile, BPD can also serve as the contrast agent for enhanced FLI. In particular, the PEGylated nanoliposome (PNL) encapsulated BPD (LBPD) was produced for contrast enhanced dual-modal FLI and PAI and imaging-guided high-e±ciency PDT. Enhanced FLI and PAI results demonstrated the signiˉcant accumulation of LBPD both within and among individual tumor during 24 h monitoring for in vivo experiment tests. In-vitro and in-vivo PDT tests were also performed, which showed that LBPD have higher PDT e±ciency and can easily break the blood vessel of tumor tissues as compared to that from BPD. It was discovered that LBPD has great potentials as a diagnosis and treatment agent for dual-modal FLI and PAI-guided PDT of cancer.

In this study, we developed a novel photoacoustic imaging technique based on poly (ethyleneglycol)-coated (PEGylated) gold nanorods (PEG-GNRs) (as the contrast agent) combined with traditional Chinese medicine (TCM) acupuncture (as the auxiliary method) for quantitatively monitoring contrast enhancement in the vasculature of a mouse brain in vivo. This study takes advantage of the strong near-infrared absorption (peak at ~700 nm) of GNRs and the ability to adjust the hemodynamics of acupuncture. Experimental results show that photoacoustic tomography (PAT) successfully reveals the optical absorption variation of the vasculature of the mouse brain in response to intravenous administration of GNRs and acupuncture at the Zusanli acupoint (ST36) both individually and combined. The quantitative measurement of contrast enhancement indicates that the composite contrast agents (integration of acupuncture and GNRs) would greatly enhance the photoacoustic imaging contrast. The quantitative results also have the potential to estimate the local concentration of GNRs and even the real-time effects of acupuncture.

Photoacoustic imaging, which can provide the maximum intensity contrast in tissue depth imaging without ionizing radiation, will be a promising imaging trend for tumor detection. In this paper, a column diffusion fiber was employed to carry a pulsed laser for irradiating stomach directly through esophagus based on the characteristics of gastric tissue structure. A long focused ultrasonic transducer was placed outside the body to detect photoacoustic signals of gastric tissue. Phantom and in vitro experiments of submucosal gastric tumors were carried out to check the sensitivity of scanning photoacoustic tomography system, including the lateral and longitudinal resolution of the system, sensitivity of different absorption coe±cient in imaging, capability of transversal detection, and probability of longitudinal detection. The results demonstrate that our innovative technique can improve the parameters of imaging. The lateral resolution reaches 2.09 mm. Then a depth of 5.5mm with a longitudinal accuracy of 0.36mm below gastric mucosa of early gastric cancer (EGC) has been achieved. In addition, the optimal absorption coe±cient differences among absorbers of system are 3.3–3.9 times. Results indicate that our photoacoustic imaging (PAI) system, is based on a long focusing transducer, can provide a potential application for detecting submucosal EGC without obvious symptoms.

Two-photon luminescence with near-infrared (NIR) excitation of upconversion nanoparticles (NPs) is of great importance in biological imaging due to deep penetration in high-scattering tissues, low auto-luminescence and good sectioning ability. Unfortunately, common two-photon luminescence is in visible band with an extremely high exciation power density, which limits its application. Here, we synthesized NaYF4:Yb/Tm@NaYF4 upconversion NPs with strong twophoton NIR emission and a low excitation power density. Furthermore, NaYF4:Yb/Tm@NaYF4@SiO2@OTMS@F127 NPs with high chemical stability were obtained by a modified multilayer coating method which was applied to upconversion NPs for the first time. In addition, it is shown that the as-prepared hydrophillic upconversion NPs have great biocompatibility and kept stable for 6 hours during in vivo whole-body imaging. The vessels with two-photon luminescence were clear even under an excitation power density as low as 25mW/cm2. Vivid visualizations of capillaries and vessels in a mouse brain were also obtained with low background and high contrast. Because of cheaper instruments and safer power density, the NIR two-photon luminescence of NaYF4:Yb/Tm@NaYF4 upconversion NPs could promote wider application of two-photon technology. The modified multilayer coating method could be widely used for upconversion NPs to increase the stable time of the in vivo circulation. Our work possesses a great potential for deep imaging and imaging-guided treatment in the future.

Structured illumination microscopy (SIM) is a promising super-resolution technique for imaging subcellular structures and dynamics due to its compatibility with most commonly used fluorescent labeling methods. Structured illumination can be obtained by either laser interference or projection of fringe patterns. Here, we proposed a fringe projector composed of a compact multiwavelength LEDs module and a digital micromirror device (DMD) which can be directly attached to most commercial inverted fluorescent microscopes and update it into a SIM system. The effects of the period and duty cycle of fringe patterns on the modulation depth of the structured light field were studied. With the optimized fringe pattern, 1:6× resolution improvement could be obtained with high-end oil objectives. Multicolor imaging and dynamics of subcellular organelles in live cells were also demonstrated. Our method provides a low-cost solution for SIM setup to expand its wide range of applications to most research labs in the field of life science and medicine.