Engineered apoptotic bodies hitchhiking across the blood-brain barrier achieved a combined photothermal-chemotherapeutic effect against glioma.

Background: Glioma as a highly lethal tumor is difficult to treat since the blood-brain barrier (BBB) restricts drug delivery into the brain. It remains a huge need for developing strategies allowing drug passage across the BBB with high efficacy. Methods: Herein, we engineered drug-loaded apoptotic bodies (Abs) loaded with doxorubicin (Dox) and indocyanine green (ICG) to cross the BBB for the treatment of glioma. The confocal laser scanning microscopy was used to characterize the structure and evaluate the hitchhiking effect of the Abs. The in vivo BBB-crossing ability and photothermal-chemotherapeutic effect of the drug-loaded Abs were investigated in mice orthotopic glioma model. Results: Engineered Abs loaded with Dox and ICG were successfully prepared. The Abs were phagocytized by macrophages, actively penetrate the BBB in vitro and in vivo utilizing the hitchhiking effect. The whole in vivo process was visualized by near-infrared fluorescence signal with a signal-to-background ratio of 7 in a mouse model of orthotopic glioma. The engineered Abs achieved a combined photothermal-chemotherapeutic effect, leading to a median survival time of 33 days in glioma-bearing mice compared to 22 days in the control group. Conclusions: This study presents engineered drug carriers with the ability to hitchhike across the BBB, providing new opportunities for the treatment of glioma.

Biomimetic Theranostic Agents with Superior NIR-II Photoacoustic and Magnetic Resonance Imaging Performance for Targeted Photothermal Therapy of Prostate Cancer.

The accurate diagnosis and treatment of prostate cancer at an early stage is crucial to reduce mortality rates. However, the limited availability of theranostic agents with active tumor-targeting abilities hinders imaging sensitivity and therapeutic efficiency. To address this challenge, we have developed biomimetic cell membrane-modified Fe2O3 nanoclusters implanted in polypyrrole (CM-LFPP), achieving photoacoustic/magnetic resonance dual-modal imaging-guided photothermal therapy of prostate cancer. The CM-LFPP exhibits strong absorption in the second near-infrared window (NIR-II, 1000-1700 nm), showing high photothermal conversion efficiency of up to 78.7% under 1064 nm laser irradiation, excellent photoacoustic imaging capabilities, and good magnetic resonance imaging ability with a T2 relaxivity of up to 48.7 s-1 mM-1. Furthermore, the lipid encapsulation and biomimetic cell membrane modification enable CM-LFPP to actively target tumors, leading to a high signal-to-background ratio of ~30.2 for NIR-II photoacoustic imaging. Moreover, the biocompatible CM-LFPP enables low-dose (0.6 W cm-2) photothermal therapy of tumors under 1064 nm laser irradiation. This technology offers a promising theranostic agent with remarkable photothermal conversion efficiency in the NIR-II window, providing highly sensitive photoacoustic/magnetic resonance imaging-guided prostate cancer therapy.

A swallowable X-ray dosimeter for the real-time monitoring of radiotherapy.

Monitoring X-ray radiation in the gastrointestinal tract can enhance the precision of radiotherapy in patients with gastrointestinal cancer. Here we report the design and performance, in the gastrointestinal tract of rabbits, of a swallowable X-ray dosimeter for the simultaneous real-time monitoring of absolute absorbed radiation dose and of changes in pH and temperature. The dosimeter consists of a biocompatible optoelectronic capsule containing an optical fibre, lanthanide-doped persistent nanoscintillators, a pH-sensitive polyaniline film and a miniaturized system for the wireless readout of luminescence. The persistent luminescence of the nanoscintillators after irradiation can be used to continuously monitor pH without the need for external excitation. By using a neural-network-based regression model, we estimated the radiation dose from radioluminescence and afterglow intensity and temperature, and show that the dosimeter was approximately five times more accurate than standard methods for dose determination. Swallowable dosimeters may help to improve radiotherapy and to understand how radiotherapy affects tumour pH and temperature.

Dual-modal molecular imaging and therapeutic evaluation of coronary microvascular dysfunction using indocyanine green-doped targeted microbubbles.

Coronary microvascular dysfunction (CMD), which causes a series of cardiovascular diseases, seriously endangers human health. However, precision diagnosis of CMD is still challenging due to the lack of sensitive probes and complementary imaging technologies. Herein, we demonstrate indocyanine green-doped targeted microbubbles (named T-MBs-ICG) as dual-modal probes for highly sensitive near-infrared (NIR) fluorescence imaging and high-resolution ultrasound imaging of CMD in mouse models. In vitro results show that T-MBs-ICG can specifically target fibrin, a specific CMD biomarker, via the cysteine-arginine-glutamate-lysine-alanine (CREKA) peptide modified on the surface of microbubbles. We further employ T-MBs-ICG to achieve NIR fluorescence imaging of injured myocardial tissue in a CMD mouse model, leading to a signal-to-background ratio (SBR) of up to 50, which is 20 fold higher than that of the non-targeted group. Furthermore, ultrasound molecular imaging of T-MBs-ICG is obtained within 60 s after intravenous injection, providing molecular information on ventricular and myocardial structures and fibrin with a resolution of 1.033 mm × 0.466 mm. More importantly, we utilize comprehensive dual-modal imaging of T-MBs-ICG to evaluate the therapeutic efficacy of rosuvastatin, a cardiovascular drug for the clinical treatment of CMD. Overall, the developed T-MBs-ICG probes with good biocompatibility exhibit great potential in the clinical diagnosis of CMD.

X-Ray Activatable Au/Ag Nanorods for Tumor Radioimmunotherapy Sensitization and Monitoring of the Therapeutic Response Using NIR-II Photoacoustic Imaging.

Radioimmunotherapy (RIT) is an advanced physical therapy used to kill primary cancer cells and inhibit the growth of distant metastatic cancer cells. However, challenges remain because RIT generally has low efficacy and serious side effects, and its effects are difficult to monitor in vivo. This work reports that Au/Ag nanorods (NRs) enhance the effectiveness of RIT against cancer while allowing the therapeutic response to be monitored using activatable photoacoustic (PA) imaging in the second near-infrared region (NIR-II, 1000-1700 nm). The Au/Ag NRs can be etched using high-energy X-ray to release silver ions (Ag+ ), which promotes dendritic cell (DC) maturation, enhances T-cell activation and infiltration, and effectively inhibits primary and distant metastatic tumor growth. The survival time of metastatic tumor-bearing mice treated with Au/Ag NR-enhanced RIT is 39 days compared with 23 days in the PBS control group. Furthermore, the surface plasmon absorption intensity at 1040 nm increases fourfold after Ag+ are released from the Au/Ag NRs, allowing X-ray activatable NIR-II PA imaging to monitor the RIT response with a high signal-to-background ratio of 24.4. Au/Ag NR-based RIT has minimal side effects and shows great promise for precise cancer RIT.

Low-Dose NIR-II Preclinical Bioimaging Using Liposome-Encapsulated Cyanine Dyes.

Fluorescence imaging in the second near-infrared window (NIR-II, 1000-1700 nm) provides a powerful tool for in vivo structural and functional imaging in deep tissue. However, the lack of biocompatible contrast agents with bright NIR-II emission has hindered its application in fundamental research and clinical trials. Herein, a liposome encapsulation strategy for generating ultrabright liposome-cyanine dyes by restricting dyes in the hydrophobic pockets of lipids and inhibiting the aggregation, as corroborated by computational modeling, is reported. Compared with free indocyanine green (ICG, an US Food and Drug Administration-approved cyanine dye), liposome-encapsulated ICG (S-Lipo-ICG) shows a 38.7-fold increase in NIR-II brightness and enables cerebrovascular imaging at only one-tenth dose over a long period (30 min). By adjusting the excitation wavelength, two liposome-encapsulated cyanine dyes (S-Lipo-ICG and S-Lipo-FD1080) enable NIR-II dual-color imaging. Moreover, small tumor nodules (2-5 mm) can be successfully distinguished and removed with S-Lipo-ICG image-guided tumor surgery in rabbit models. This liposome encapsulation maintains the metabolic pathway of ICG, promising for clinical implementation.

Albumin-Consolidated AIEgens for Boosting Glioma and Cerebrovascular NIR-II Fluorescence Imaging.

The application of an exogenous polymer matrix to construct aggregation-induced emission (AIE) nanoprobes promotes the utility of AIE luminogens (AIEgens) in diagnosing brain diseases. However, the limited fluorescence (FL) and low active-targeting abilities of AIE-based nanoprobes impede their imaging application. Here, we employed endogenous albumin as an effective matrix to encapsulate AIEgens to enhance FL quantum yield (QY) and active-targeting ability. The albumin-consolidated strategy effectively inhibited the intramolecular vibration of AIEgens and enhanced endocytosis mediated by the gp60 receptor. The QYs of three kinds of albumin-based AIE nanoprobes with FL emissions ranging from the visible (400-650 nm) to the second near-infrared (NIR-II, 1000-1700 nm) region was at least 10% higher, and the tumor-targeting efficiency was ∼25% higher, compared with those of nanoprobes constructed by the exogenous polymer. Albumin-based AIE nanoprobes have achieved active-targeting NIR-II imaging of brain tumors and cerebrovascular imaging with a high signal-to-background ratio (SBR, ∼90) and high resolution (∼70 µm) in mouse models. Therefore, the albumin-based AIE nanoprobes will enable FL imaging-guided surgery of brain tumors and cerebral ischemia, which will improve surgical efficacy to prevent recurrence and side effects.

NIR-II fluorescence visualization of ultrasound-induced blood-brain barrier opening for enhanced photothermal therapy against glioblastoma using indocyanine green microbubbles.

Focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening is crucial for enhancing glioblastoma (GBM) therapies. However, an in vivo imaging approach with a high spatial-temporal resolution to monitor the BBB opening process in situ and synchronously is still lacking. Herein, we report the use of indocyanine green (ICG)-dopped microbubbles (MBs-ICG) for visualizing the FUS-induced BBB opening and enhancing the photothermal therapy (PTT) against GBM. The MBs-ICG show bright fluorescence in the second near-infrared window (NIR-II), ultrasound contrast, and ultrasound-induced size transformation properties. By virtue of complementary contrast properties, MBs-ICG can be successfully applied for cerebral vascular imaging with NIR-II fluorescence resolution of ∼168.9 µm and ultrasound penetration depth of ∼7 mm. We further demonstrate that MBs-ICG can be combined with FUS for in situ and synchronous visualization of the BBB opening with a NIR-II fluorescence signal-to-background ratio of 6.2 ± 1.2. Finally, our data show that the MBs-ICG transform into lipid-ICG nanoparticles under FUS irradiation, which then rapidly penetrate the tumor tissues within 10 min and enhance PTT in orthotopic GBM-bearing mice. The multifunctional MBs-ICG approach provides a novel paradigm for monitoring BBB opening and enhancing GBM therapy.

Miniature NIR-II Nanoprobes for Active-Targeted Phototheranostics of Brain Tumors.

Nanoprobes (NPs) in the second near-infrared biowindow (NIR-II, 1000-1700 nm) are developed and widely used in cancer phototheranostics. However, most NIR-II NPs exhibit low phototheranostic efficiency due to their tedious synthetic routes, large particle sizes (>20 nm), and lack of active targeting properties. Here, miniature NIR-II NPs, named HSA-ICG-iRGD, for active-targeted NIR-II phototheranostics of brain tumors are reported. The HSA-ICG-iRGD probes are designed based on hydrophobic interactions as well as hydrogen bonds between albumin and indocyanine green derivatives (ICG-iRGD) via molecular docking. The as-prepared NPs have a compact size of 10 nm and show tumor-targeting ability by specifically binding to αv ß3 integrin receptors which are highly expressed on the surface of brain tumor cells via iRGD peptides. The HSA-ICG-iRGD NPs are then applied to perform active-targeted NIR-II fluorescence imaging, resulting in a signal-to-background ratio of 6.85 in orthotopic glioma mouse models. Under the selected laser irradiation of 808 nm, the photothermal effect of HSA-ICG-iRGD extends the survival of the tumor-bearing mice to 55 days, significantly longer than that of the control group (30 days). These results highlight the potential of miniature NPs for active-targeted NIR-II fluorescence imaging and phototherapy of brain tumors.

Cell-Membrane Biomimetic Indocyanine Green Liposomes for Phototheranostics of Echinococcosis.

Echinococcosis is an important zoonotic infectious disease that seriously affects human health. Conventional diagnosis of echinococcosis relies on the application of large-scale imaging equipment, which is difficult to promote in remote areas. Meanwhile, surgery and chemotherapy for echinococcosis can cause serious trauma and side effects. Thus, the development of simple and effective treatment strategies is of great significance for the diagnosis and treatment of echinococcosis. Herein, we designed a phototheranostic system utilizing neutrophil-membrane-camouflaged indocyanine green liposomes (Lipo-ICG) for active targeting the near-infrared fluorescence diagnosis and photothermal therapy of echinococcosis. The biomimetic Lipo-ICG exhibits a remarkable photo-to-heat converting performance and desirable active-targeting features by the inflammatory chemotaxis of the neutrophil membrane. In-vitro and in-vivo studies reveal that biomimetic Lipo-ICG with high biocompatibility can achieve in-vivo near-infrared fluorescence imaging and phototherapy of echinococcosis in mouse models. Our research is the first to apply bionanomaterials to the phototherapy of echinococcosis, which provides a new standard for the convenient and noninvasive detection and treatment of zoonotic diseases.

High-Specificity In Vivo Tumor Imaging Using Bioorthogonal NIR-IIb Nanoparticles.

Lanthanide-based NIR-IIb nanoprobes are ideal for in vivo imaging. However, existing NIR-IIb nanoprobes often suffer from low tumor-targeting specificity, limiting their widespread use. Here the application of bioorthogonal nanoprobes with high tumor-targeting specificity for in vivo NIR-IIb luminescence imaging and magnetic resonance imaging (MRI) is reported. These dual-modality nanoprobes can enhance NIR-IIb emission by 20-fold and MRI signal by twofold, compared with non-bioorthogonal nanoprobes in murine subcutaneous tumors. Moreover, these bioorthogonal probes enable orthotopic brain tumor imaging. Implementation of bio-orthogonal chemistry significantly reduces the nanoprobe dose and hence cytotoxicity, providing a paradigm for real-time in vivo visualization of tumors.

Temperature-Feedback Nanoplatform for NIR-II Penta-Modal Imaging-Guided Synergistic Photothermal Therapy and CAR-NK Immunotherapy of Lung Cancer.

In this study, to visually acquire all-round structural and functional information of lung cancer while performing synergistic photothermal therapy (PTT) and tumor-targeting immunotherapy, a theranostic nanoplatform that introduced upconversion nanoparticles (UCNPs) and IR-1048 dye into the lipid-aptamer nanostructrure (UCILA) is constructed. Interestingly, the IR-1048 dye grafted into the lipid bilayer can serve as the theranostic agent for photoacoustic imaging, optical coherence tomography angiography, photothermal imaging, and PTT in the second near infrared (NIR-II) window. In addition, loaded in the inner part of UCILA, UCNPs possess the superior luminescence property and high X-ray attenuation coefficient, which can act as contrast agents for computed tomography (CT) and thermo-sensitive up-conversion luminescence (UCL) imaging, enabling real-time tracking of metabolic activity of tumor and temperature-feedback PTT. Furthermore, under the complementary guidance of penta-modal imaging and an accurate monitoring of in situ temperature change during PTT, UCILA exhibits its excellent capability for ablating the lung tumor with minimal side effects. Meanwhile, synergistic CAR-NK immunotherapy is carried out specifically to eradicate any possible residual tumor cells after PTT. Therefore, the UCILA nanoplatform is demonstrated as a multifunctional theranostic agent for both penta-modal imaging and temperature-feedback PTT while conducting targeting immunotherapy of lung cancer.

Metabolizable Near-Infrared-II Nanoprobes for Dynamic Imaging of Deep-Seated Tumor-Associated Macrophages in Pancreatic Cancer.

Tumor-associated macrophages (TAMs) play a crucial part in cancer evolution. Dynamic imaging of TAMs is of great significance for treatment outcome evaluation and precision tumor therapy. Currently, most fluorescence nanoprobes tend to accumulate in the liver and are difficult to metabolize, which leads to strong background signals and inadequate imaging quality of TAMs nearby the liver such as pancreatic cancer. Herein, we aim to develop metabolizable dextran-indocyanine green (DN-ICG) nanoprobes in the second near-infrared window (NIR-II, 1 000-1 700 nm) for dynamic imaging of TAMs in pancreatic cancer. Compared to free ICG, the NIR-II fluorescence intensity of DN-ICG nanoprobes increased by 279% with significantly improved stability. We demonstrated that DN-ICG nanoprobes could specifically target TAMs through the interaction of dextran with specific ICAM-3-grabbing nonintegrin related 1 (SIGN-R1), which were highly expressed in TAMs. Subsequently, DN-ICG nanoprobes gradually metabolized in the liver yet remained in pancreatic tumor stroma in mouse models, achieving a high signal-to-background ratio (SBR = 7) in deep tissue (∼0.5 cm) NIR-II imaging of TAMs. Moreover, DN-ICG nanoprobes could detect dynamic changes of TAMs induced by low-dose radiotherapy and zoledronic acid. Therefore, the highly biocompatible and biodegradable DN-ICG nanoprobes harbor great potential for precision therapy in pancreatic cancer.

Intravital NIR-II three-dimensional photoacoustic imaging of biomineralized copper sulfide nanoprobes.

Photoacoustic (PA) imaging with functional nanoprobes in the second near-infrared region (NIR-II, 1000-1700 nm) has aroused much interest due to its deep tissue penetration and high maximum laser permissible exposure. However, most NIR-II PA imaging is performed using the two-dimensional (2D) imaging modality, which impedes the comprehension of the in vivo biodistribution, angiography and molecular-targeted performance of NIR-II nanoprobes (NPs). Herein, we report the systematic monitoring of biomineralized copper sulfide (CuS) NPs, typical NIR-II NPs, in mouse models by employing NIR-II three-dimensional (3D) PA imaging. The advanced imaging modality provides dynamic information about the 3D biodistribution and metabolic pathway of CuS NPs. We also achieved contrast-enhanced 3D PA imaging of abdominal and cerebral vessels at a high signal-to-background ratio. Moreover, the tumor-targeted CuS NPs conjugated with the bombesin peptide endowed NIR-II 3D PA with superior performance in imaging orthotopic tumors both deep in the prostate and in the brain beneath the intact scalp and skull. Our results highlight the potential of NIR-II 3D PA imaging for the evaluation of the in vivo behavior of NPs, thus providing a promising strategy for screening NPs in clinical translational studies.

Tiny 2D silicon quantum sheets: a brain photonic nanoagent for orthotopic glioma theranostics.

We report that atomically thin two-dimensional silicon quantum sheets (2D Si QSs), prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation, can serve as a high-performance brain photonic nanoagent for orthotopic glioma theranostics. With the lateral size of approximately 14.0 nm and thickness of about 1.6 nm, tiny Si QSs possess high mass extinction coefficient of 27.5 L g-1 cm-1 and photothermal conversion efficiency of 47.2% at 808 nm, respectively, concurrently contributing to the best photothermal performance among the reported 2D mono-elemental materials (Xenes). More importantly, Si QSs with low toxicity maintain the trade-off between stability and degradability, paving the way for practical clinical translation in consideration of both storage and action of nanoagents. In vitro Transwell filter experiment reveals that Si QSs could effectively go across the bEnd.3 cells monolayer. Upon the intravenous injection of Si QSs, orthotopic brain tumors are effectively inhibited under the precise guidance of photoacoustic imaging, and the survival lifetime of brain tumor-bearing mice is increased by two fold. Atomically thin Si QSs with strong light-harvesting capability are expected to provide an effective and robust 2D photonic nanoplatform for the management of brain diseases.

Active-Targeting NIR-II Phototheranostics in Multiple Tumor Models Using Platelet-Camouflaged Nanoprobes.

Cancer phototheranostics in the second near-infrared window (NIR-II, 1000-1700 nm) has recently attracted much attention owing to its high efficacy and good safety compared with that in the first near-infrared window (NIR-I, 650-950 nm). However, the lack of theranostic nanoagents with active-targeting features limits its further application in cancer precision therapies. Herein, we constructed platelet-camouflaged nanoprobes with active-targeting characteristics for NIR-II cancer phototheranostics. The as-prepared biomimetic nanoprobes can not only escape phagocytosis by macrophages but also specifically bind to CD44 on the surface of most cancer cells. We evaluated the active-targeting performance of biomimetic nanoprobes in pancreatic cancer, breast cancer, and glioma mouse models and achieved NIR-II photoacoustic imaging with a high signal-to-background ratio and photothermal treatment with excellent tumor growth inhibition. Our results show the great potential of platelet-camouflaged nanoprobes with NIR-II active-targeting features for cancer precision diagnosis and efficient therapies.

NIR II-Excited and pH-Responsive Ultrasmall Nanoplatform for Deep Optical Tissue and Drug Delivery Penetration and Effective Cancer Chemophototherapy.

The limited tumor tissue penetration of many nanoparticles remains a formidable challenge to their therapeutic efficacy. Although several photonanomedicines have been applied to improve tumor penetration, the first near-infrared window mediated by the low optical tissue penetration depth severely limits their anticancer effectiveness. To achieve deep optical tissue and drug delivery penetration, a near-infrared second window (NIR-II)-excited and pH-responsive ultrasmall drug delivery nanoplatform was fabricated based on BSA-stabilized CuS nanoparticles (BSA@CuS NPs). The BSA@CuS NPs effectively encapsulated doxorubicin (DOX) via strong electrostatic interactions to form multifunctional nanoparticles (BSA@CuS@DOX NPs). The BSA@CuS@DOX NPs had an ultrasmall size, which allowed them to achieve deeper tumor penetration. They also displayed stronger NIR II absorbance-mediated deep optical tissue penetration than that of the NIR I window. Moreover, the multifunctional nanoplatform preferentially accumulated in tumor sites, induced tumor hyperthermia, and generated remarkably high ROS levels in tumor sites upon NIR-II laser (1064 nm) irradiation. More importantly, our strategy achieved excellent synergistic effects of chemotherapy and phototherapy (chemophototherapy) under the guidance of photothermal imaging. The developed nanoparticles also showed good biocompatibility and bioclearance properties. Therefore, our work demonstrated a facile strategy for fabricating a multifunctional nanoplatform that is a promising candidate for deep tumor penetration as an effective antitumor therapy.

Ultrasmall theranostic nanozymes to modulate tumor hypoxia for augmenting photodynamic therapy and radiotherapy.

Photodynamic therapy (PDT) and radiotherapy (RT) are oxygen-dependent treatment strategies for solid tumors in clinics. However, the hypoxic tumor microenvironment induced by uncontrolled cancer cell proliferation significantly reduces the therapeutic efficacy of these strategies. Here, we rationally constructed indocyanine green (ICG)-loaded ultrasmall gold nanoclusters (Au NCs-ICG) as theranostic nanozymes for modulating tumor hypoxia and augmenting cancer PDT and RT, respectively. The constructed Au NC-ICG nanozymes with an ultrasmall particle size (∼1 nm) exhibited favorable renal clearance performance, high substrate affinity (Km≈ 2 mM) and good catalase-like activity (Vmax≈ 4.55 × 10-3 mM s-1). In 4T1 tumor-bearing mouse models, high tumor accumulation of Au NC-ICG nanozymes was clearly visualized by near-infrared fluorescence, photoacoustic and computed tomography imaging, showing the potential for the monitoring and guidance of PDT and RT. In addition, the Au NCs-ICG nanozymes effectively decomposed intratumoral H2O2 into O2 for overcoming hypoxia and subsequently enhancing PDT and RT, respectively. Moreover, the inherent X-ray absorption capacity of Au NCs-ICG greatly deposited radiation energy within the tumor region and further improved cancer RT. The integration of multimodal imaging, tumor hypoxia regulation, and effective therapy into ultrasmall Au NCs-ICG nanozymes shows great potential for cancer theranostic applications.

Molecular Engineering of Near-Infrared Light-Responsive BODIPY-Based Nanoparticles with Enhanced Photothermal and Photoacoustic Efficiencies for Cancer Theranostics.

Background: Engineering a single organic-molecule-based nanoparticle integrating precise diagnosis and effective therapy is of great significance for cancer treatment and future clinical applications but remains a great challenge. The goal of this study is to explore small organic molecule-based nanoparticles with high photothermal conversion efficiency for photoacoustic imaging-guided therapy. Methods: Heptacyclic B, O-chelated BODIPY structure (namely Boca-BODIPY) with strong near-infrared (NIR) absorption was designed as a theranostic agent through simply molecular engineering, in which heavy atoms and alkyl chains were introduced to promote its application for tumor theranostics. The Boca-BODIPY molecules are further encapsulated in reduced bovine serum albumin (BSA) through self-assembly. Results: The BSA-Boca-BODIPY exhibited excellent biocompatibility, extraordinary stability and high photothermal conversion efficiency up to 58.7%. The nanoparticles could dramatically enhance photoacoustic contrast of the tumor region, and the signal-to-noise ratio was increased about 14 times at 10 h post intravenous injection in 4T1 tumor-bearing mice. In addition, the nanoassemblies can efficiently convert laser energy (808 nm, 0.75 w cm-2, 5min) into hyperthermia for tumor ablation. Under the photoacoustic imaging-guided photothermal therapy (PTT), the 4T1 cancer cells were efficiently killed, no tumor recurrence and PTT-induced toxicity is observed. Conclusions: Molecular engineering is a promising way to design organic-molecule-based nanoparticles for cancer theranostics. Other organic-molecule-based nanoparticles which show great promise for imaging-guided cancer precision therapy can be engineered through this method.