Enhanced Tumor Imaging Research Articles

Recent Advances in Silica-Based Nanomaterials for Enhanced Tumor Imaging and Therapy.

Cancer remains a formidable challenge, inflicting profound physical, psychological, and financial burdens on patients. In this context, silica-based nanomaterials have garnered significant attention for their potential in tumor imaging and therapy owing to their exceptional properties, such as biocompatibility, customizable porosity, and versatile functionalization capabilities. This review meticulously examines the latest advancements in the application of silica-based nanomaterials for tumor imaging and therapy. It underscores their potential in enhancing various cancer imaging modalities, including fluorescence imaging, magnetic resonance imaging, computed tomography, positron emission tomography, ultrasound imaging, and multimodal imaging approaches. Moreover, the review delves into their therapeutic efficacy in chemotherapy, radiotherapy, phototherapy, immunotherapy, gas therapy, sonodynamic therapy, chemodynamic therapy, starvation therapy, and gene therapy. Critical evaluations of the biosafety profiles and degradation pathways of these nanomaterials within biological environments are also presented. By discussing the current challenges and prospects, this review aims to provide a nuanced perspective on the clinical translation of silica-based nanomaterials, thereby highlighting their promise in revolutionizing cancer diagnostics, enabling real-time monitoring of therapeutic responses, and advancing personalized medicine.

WazaGaY: An Innovative Aza-BODIPY-Derived Near-Infrared Fluorescent Probe for Enhanced Tumor Imaging.

Aza-BODIPYs represent a class of fluorophores in which the π-conjugated system is rigidified and stabilized by a boron atom. A promising strategy to enhance their fluorescence properties involves replacing the boron atom with a metal ion. Here, we describe the synthesis and characterization of a water-soluble derivative where the metal is a gallium(III) ion, termed WazaGaY (water-soluble aza-GaDIPY). Water solubility is ensured by two ammonium substituents, inducing a bathochromic shift and a significant increase in quantum yield compared to that of the dimethylamino analog. The cellular behavior of WazaGaY-1 was observed across different tumor cells. In vivo, the distribution and safety profiles were determined, and tumor uptake was assessed in various tumor types. Following intravenous injection, WazaGaY-1 enabled clear discrimination of tumors engrafted subcutaneously in mice with high tumor-to-muscle ratios (ranging from 7 to 20), even in the absence of specific conjugation. Its potential as a contrast agent for fluorescence-guided surgery was confirmed.

A Simple Binary Supramolecular Co-Assembly Platform for Enhanced Tumor Imaging and Therapy.

The primary challenges in tumor imaging and therapy revolve around improving targeting efficiency, enhancing probe/drug delivery efficacy, and minimizing off-target signals and toxicity. Although various carriers have been developed, many are difficult to synthesize, costly, and not universally applicable. Furthermore, numerous carriers exhibit limited delivery rates in solid tumors, particularly larger nanocarriers. To address these challenges, a simple binary co-assembly drug delivery platform has been designed using the readily synthesized small molecule Cys(SEt)-Lys-CBT (CKCBT) as the self-assembly building block. CKCBT can effectively penetrate tumor cells due to its positively charged Lys side chain and small size. Upon glutathione reduction, CKCBT co-assembles with Nile red or Chlorin e6 to form nanofibers inside tumor cells. This enables their specific accumulation in tumor cells rather than normal cells and extends their exposure time, resulting in precise and enhanced tumor imaging and treatment. Hence, this uncomplicated and highly efficient binary co-assembly drug delivery platform can be easily adapted to a broad spectrum of probes and drugs, presenting a novel approach for advancing clinical diagnosis and therapy.

Hollow magnetic vortex nanorings loaded with quercetin encapsulated in polydopamine: A high-performance, intelligent nanotheranostic platform for enhanced tumor imaging and dual thermal treatment

Nanoparticle-mediated thermotherapeutic research strives innovative, multifunctional, efficient, and safe treatments. Our study introduces a novel nanoplatform: the hollow magnetic vortex nanorings within a polydopamine layer (HMVNp), which exhibit dual functionality as magnetic and photothermal agents. Utilizing a “Dual-mode” approach, combining an alternating magnetic field (AMF) with near-infrared (NIR) laser irradiation, HMVNp demonstrated a significant enhancement in heating efficacy (58 ± 8 %, SAR = 1441 vs 1032 W/g) over traditional solid magnetite nanoparticles coated with polydopamine (SMNp). The unique geometry larger surface area to volume ratio facilitates efficient magnetic vortex dynamics and enhanced heat transfer. Addressing the challenge of heat resistant heat shock protein (Hsp) expression, encapsulated quercetin (Q) within HMVNp leverages tumor acidity and dual-mode thermal therapy to enhance release, showing a 28.8 ± 6.81 % increase in Q loading capacity compared to traditional SMNp. Moreover, HMVNp significantly improves contrast for both magnetic resonance imaging (MRI) and photoacoustic imaging (PAI), with an approximately 62 % transverse relaxation (R2 = 81.5 vs 31.6 mM-1s−1 [Fe]). In vivo studies showed that while single treatments slowed tumor growth, dual-mode therapy with quercetin significantly reduced tumors and effectively prevented metastases. Our study highlights the potential of HMVNp/Q as a versatile agent in thermotherapeutic interventions, offering improved diagnostic imaging capabilities.

Transcytosis-Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging.

Transcytosis-based tubular reabsorption of endogenous proteins is a well-known energy-saving pathway that prevents nutrient loss. However, utilization of this well-known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2-targeted Gly-Sar peptide as a ligand, renal-clearable luminescent gold nanoparticles (P-AuNPs) were developed as protein mimics to investigate the transcytosis-based tubular reabsorption of exogenous substances. By regulating the influential factors (H+ content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly-Sar-mediated transcytosis, the specific and efficient interaction between P-AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P-AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high-contrast tumor imaging.

Transcytosis‐Based Renal Tubular Reabsorption of Luminescent Gold Nanoparticles for Enhanced Tumor Imaging

AbstractTranscytosis‐based tubular reabsorption of endogenous proteins is a well‐known energy‐saving pathway that prevents nutrient loss. However, utilization of this well‐known reabsorption pathway for the delivery of exogenous nanodrugs remains a challenge. In this study, using the surface mimic strategy of a specific PEPT1/2‐targeted Gly−Sar peptide as a ligand, renal‐clearable luminescent gold nanoparticles (P−AuNPs) were developed as protein mimics to investigate the transcytosis‐based tubular reabsorption of exogenous substances. By regulating the influential factors (H+ content in tubular lumens and PEPT1/2 transporter counts in tubular cells) of Gly−Sar‐mediated transcytosis, the specific and efficient interaction between P−AuNPs and renal tubular cells was demonstrated both in vitro and in vivo. Efficient transcellular transportation significantly guided the reabsorption of P−AuNPs back into the bloodstream, which enhanced the blood concentration and bioavailability of nanoparticles, contributing to high‐contrast tumor imaging.

Tumor-tropic Trojan horses: Using mesenchymal stem cells as cellular nanotheranostics.

Various classes of nanotheranostics have been developed for enhanced tumor imaging and therapy. However, key limitations for a successful use of nanotheranostics include their targeting specificity with limited off-site tissue accumulation as well as their distribution and prolonged retention throughout the entire tumor. Due to their inherent tumor-tropic properties, the use of mesenchymal stem cells (MSCs) as a "Trojan horse" has recently been proposed to deliver nanotheranostics more effectively. This review discusses the current status of "cellular nanotheranostics" for combined (multimodal) imaging and therapy in preclinical cancer models. Emphasis is placed on the limited knowledge of the signaling pathways and molecular mechanisms of MSC tumor-tropism, and how such information may be exploited to engineer MSCs in order to further improve tumor homing and nanotheranostic delivery using image-guided procedures.

MnO2/Ce6 microbubble-mediated hypoxia modulation for enhancing sono-photodynamic therapy against triple negative breast cancer.

Sono-photodynamic therapy (SPDT) has emerged as a promising treatment modality for triple negative breast cancer (TNBC). However, the hypoxic tumor microenvironment hinders the application of SPDT. Herein, in this study, a multifunctional platform (MnO2/Ce6@MBs) was designed to address this issue. A sono-photosensitizer (Ce6) and a hypoxia modulator (MnO2) were loaded into microbubbles and precisely released within tumor tissues under ultrasound irradiation. MnO2in situ reacted with the excess H2O2 and H+ and produced O2 within the TNBC tumor, which alleviated hypoxia and augmented SPDT by increasing ROS generation. Meanwhile, the reaction product Mn2+ was able to achieve T1-weighted MRI for enhanced tumor imaging. Additionally, Ce6 and microbubbles served as a fluorescence imaging contrast agent and a contrast-enhanced ultrasound imaging agent, respectively. In in vivo anti-tumor studies, under the FL/US/MR imaging guidance, MnO2/Ce6@MBs combined with SPDT significantly reversed tumor hypoxia and inhibited tumor growth in 4T1-tumor bearing mice. This work presents a theragnostic system for reversing tumor hypoxia and enhancing TNBC treatment.

Biotin‐Conjugated Poly(Acrylic Acid)‐Grafted Ultrasmall Gadolinium Oxide Nanoparticles for Enhanced Tumor Imaging

AbstractHerein, biotin (Bio)‐conjugated poly(acrylic acid) (PAA)‐grafted ultrasmall gadolinium oxide nanoparticles (Bio‐PAA‐Gd2O3 NPs) were synthesized for enhanced tumor imaging using Bio as a tumor‐targeting ligand. The average particle diameter of Gd2O3 NPs was 2.1 nm. The Bio‐PAA‐Gd2O3 NPs exhibited excellent colloidal stability (i. e., no precipitation) and a high longitudinal water proton spin relaxivity (r1) of 23.8 s−1 mM−1 (r2/r1=1.6 and r2=transverse water proton spin relaxivity), which was ∼6 times higher than those of commercial Gd‐chelated magnetic resonance imaging (MRI) contrast agents. Cytotoxicity tests using two cell lines showed that the Bio‐PAA‐Gd2O3 NPs were almost non‐toxic up to the measured concentration of 500 μM Gd. The enhanced tumor imaging of the Bio‐PAA‐Gd2O3 NPs was demonstrated through their higher positive contrasts and longer contrast retention at the tumor after intravenous injection in T1 MR images, compared with those of the control PAA‐Gd2O3 NPs.

Planted Graphene Quantum Dots for Targeted, Enhanced Tumor Imaging and Long-Term Visualization of Local Pharmacokinetics.

While photoluminescent graphene quantum dots (GQDs) have long been considered very suitable for bioimaging owing to their protein-like size, superhigh photostability and in vivo long-term biosafety, their unique and crucial bioimaging applications in vivo remain unreachable. Herein, planted GQDs are presented as an excellent tool for in vivo fluorescent, sustainable and multimodality tumor bioimaging in various scenarios. The GQDs are in situ planted in the poly(ethylene glycol) (PEG) layer of PEGylated nanoparticles via a bottom-up molecular approach to obtain the NPs-GQDs-PEG nanocomposite. The planted GQDs show more than four times prolonged blood circulation and 7-8 times increased tumor accumulation than typical GQDs in vivo. After accessible specificity modification, the multifunctional NPs-GQDs-PEG provides targeted, multimodal molecular imaging for various tumor models in vitro or in vivo. Moreover, the highly photostable GQDs enable long-term, real-time visualization of the local pharmacokinetics of NPs in vivo. Planting GQDs in PEGylated nanomedicine offers a new strategy for broad in vivo biomedical applications of GQDs.

Phosphorus core-shell tecto dendrimers for enhanced tumor imaging: the rigidity of the backbone matters.

Nanoplatforms with amplified passive tumor targeting and enhanced protein resistance can evade unnecessary uptake by the reticuloendothelial system and achieve high tumor retention for accurate tumor theranostics. To achieve this goal, we here constructed phosphorus core-shell tecto dendrimers (CSTDs) with a rigid aromatic backbone core as a nanoplatform for enhanced fluorescence and single-photon emission computed tomography (SPECT) dual-mode imaging of tumors. In this study, the phosphorus P-G2.5/G3 CSTDs (G denotes generation) were partially conjugated with tetraazacyclododecane tetraacetic acid (DOTA), cyanine5.5 (Cy5.5) and 1,3-propane sulfonate (1,3-PS) and then labeled with 99mTc. The formed P-G2.5/G3-DOTA-Cy5.5-PS CSTDs possess good monodispersity with a particle size of 10.1 nm and desired protein resistance and cytocompatibility. Strikingly, compared to the counterpart material G3/G3-DOTA-Cy5.5-PS with both the core and shell components being soft poly(amidoamine) dendrimers, the developed P-G2.5/G3-DOTA-Cy5.5-PS complexes allow for more efficient cellular uptake and more significant penetration in 3-dimensional tumor spheroids in vitro, as well as more significant tumor retention and accumulation for enhanced dual-mode fluorescence and SPECT (after labelling with 99mTc) tumor imaging in vivo. Our studies suggest that the rigidity of the core for the constructed CSTDs matters in the amplification of the tumor enhanced permeability retention (EPR) effect for improved cancer nanomedicine development.

A tumor-targetable NIR probe with photoaffinity crosslinking characteristics for enhanced imaging-guided cancer phototherapy.

Spatiotemporally manipulating the in situ immobilization of theranostic agents within cancer cells to improve their bioavailability is highly significant yet challenging in tumor diagnosis and treatment. Herein, as a proof-of concept, we for the first time report a tumor-targetable near-infrared (NIR) probe DACF with photoaffinity crosslinking characteristics for enhanced tumor imaging and therapeutic applications. This probe possesses great tumor-targeting capability, intensive NIR/photoacoustic (PA) signals, and a predominant photothermal effect, allowing for sensitive imaging and effective photothermal therapy (PTT) of tumors. Most notably, upon 405 nm laser illumination, DACF could be covalently immobilized within tumor cells through a photocrosslinking reaction between photolabile diazirine groups and surrounding biomolecules resulting in enhanced tumor accumulation and prolonged retention simultaneously, which significantly facilitates the imaging and PTT efficacy of tumor in vivo. We therefore believe that our current approach would provide a new insight for achieving precise cancer theranostics.

Mono and Multiple Tumor-Targeting Ligand-Coated Ultrasmall Gadolinium Oxide Nanoparticles: Enhanced Tumor Imaging and Blood Circulation.

Hydrophilic and biocompatible PAA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.7 nm) were synthesized and conjugated with tumor-targeting ligands, i.e., cyclic arginylglycylaspartic acid (cRGD) and/or folic acid (FA). FA-PAA-Gd2O3 and cRGD/FA-PAA-Gd2O3 nanoparticles were successfully applied in U87MG tumor-bearing mice for tumor imaging using T1 magnetic resonance imaging (MRI). cRGD/FA-PAA-Gd2O3 nanoparticles with multiple tumor-targeting ligands exhibited higher contrasts at the tumor site than FA-PAA-Gd2O3 nanoparticles with mono tumor-targeting ligands. In addition, the cRGD/FA-PAA-Gd2O3 nanoparticles exhibited higher contrasts in all organs, especially the aorta, compared with those of the FA-PAA-Gd2O3 nanoparticles, because of the blood cell hitchhiking effect of cRGD in the cRGD/FA-PAA-Gd2O3 nanoparticles, which prolonged their circulation in the blood.

Enhanced Tumor Imaging Using Glucosamine-Conjugated Polyacrylic Acid-Coated Ultrasmall Gadolinium Oxide Nanoparticles in Magnetic Resonance Imaging.

Owing to a higher demand for glucosamine (GlcN) in metabolic processes in tumor cells than in normal cells (i.e., GlcN effects), tumor imaging in magnetic resonance imaging (MRI) can be highly improved using GlcN-conjugated MRI contrast agents. Here, GlcN was conjugated with polyacrylic acid (PAA)-coated ultrasmall gadolinium oxide nanoparticles (UGONs) (davg = 1.76 nm). Higher positive (brighter or T1) contrast enhancements at various organs including tumor site were observed in human brain glioma (U87MG) tumor-bearing mice after the intravenous injection of GlcN-PAA-UGONs into their tail veins, compared with those obtained with PAA-UGONs as control, which were rapidly excreted through the bladder. Importantly, the contrast enhancements of the GlcN-PAA-UGONs with respect to those of the PAA-UGONs were the highest in the tumor site owing to GlcN effects. These results demonstrated that GlcN-PAA-UGONs can serve as excellent T1 MRI contrast agents in tumor imaging via GlcN effects.

Driving Forces Sorted In Situ Size‐Increasing Strategy for Enhanced Tumor Imaging and Therapy

Nanoparticles (NPs) with diverse functionalities are widely used in tumor diagnostic and therapeutic. However, the therapeutic efficiency is unsatisfactory because of the limited penetration depth as well as short retention time in a solid tumor, resulting in the inaccessibility of NPs and low tumor treatment efficiency. Therefore, it is of extreme vital significance to design NPs for simultaneously realizing deep penetration and long retention. Considering that the smaller‐sized NPs may penetrate deeply in tumor and large‐sized NPs show enhanced retention, many kinds of in situ size‐increasing strategies of NPs have recently been developed for precise tumor imaging and therapy. In this review, the recent progress of stimuli‐induced size increasing of NPs in vivo according to the driving forces inducing the aggregation of the smaller entity into bigger one with ordered or unordered structures in disease sites is summarized. The biomedical applications of the size‐increasing strategy in the field of tumor imaging and therapeutics are introduced. Finally, the potential challenges underlying this strategy are briefly listed and its possible future clinical transformation directions are envisioned.

Stereotactic body radiotherapy (SBRT) with functional treatment planning in patients with hepatocellular carcinoma (HCC) and advanced hepatic cirrhosis: Survival outcomes and toxicity.

460 Background: To evaluate outcomes and dosimetric parameters of ablative stereotactic body radiotherapy (SBRT) with functional treatment planning for localized hepatocellular carcinoma (HCC) in patients with Child-Pugh B (CP-B) hepatic cirrhosis. Methods: Liver SPECT with 99mTc-sulfur colloid was co-registered to 3D-CT for identification and avoidance of functional hepatic parenchyma during SBRT in patients with advanced cirrhosis. Functional liver volumes (FLV-SPECT) were compared to anatomical liver volumes, as were dosimetric parameters when radiation dose constraints were adapted exclusively to FLV-SPECT. Hepatic function, toxicity, and radiographic response were documented every 4–6 months following SBRT. Results: With a median follow-up of 25 months 37 patients (48 lesions treated) with CP-B cirrhosis received SBRT to a median dose 48 Gy (4–5 fractions). FLV-SPECT volume loss (509 cc or 41.3%, p < 0.001) was observed in all patients, while the functional and anatomical liver volumes matched well in a control group of non-cirrhotic/non-HCC patients. While tumors received ablative irradiation, mean dose to FLV-SPECT was maintained at 1.3 – 16 Gy (median 9.17 Gy), well below the liver threshold tolerance to radiation. Seventeen patients successfully completed liver transplant at a median time to transplant of 6.5 months. The dropout rate from the transplant list was 9 % with intrahepatic progression outside treated tumors. Eight of 10 patients with intrahepatic progression received additional SBRT during follow-up. Overall 2-year survival rate was 65% with no incidence of RILD or CP class migration from B to C was observed at 6+ months post SBRT. Two patients completed liver SBRT on a hybrid linear accelerator combined with MRI scanner (Unity MR-Linac, Elekta) utilizing Super-Paramagnetic Iron Oxide (SPIO) nanoparticle agent as an alternative contrast media for functionally active liver parenchyma. Prolonged SPIO-contrast retention also allowed per fraction treatment plan adaptation and enhanced tumor imaging. Conclusions: SBRT planning with 99mTc sulfur colloid SPECT allows identification and conformal avoidance of residual functionally active hepatic parenchyma in patients with CP-B cirrhosis. We report high local control and low toxicity leading to satisfactory pre- and post-liver transplant outcomes. Prospective clinical trial investigating MRI-SPIO functional treatment planning for liver SBRT is ongoing at our institution.

Tumor-Targeted ZW800-1 Analog for Enhanced Tumor Imaging and Photothermal Therapy.

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

99mTc-Methionine Gold Nanoparticles as a Promising Biomaterial for Enhanced Tumor Imaging.

Methionine-gold nanoparticles (MGNs) was synthesized by conjugating methionine via dithiocarbamate linkage to gold nanoparticles (GNPs), prepared simultaneously by one pot modified Burst method. Formation of MGNs was confirmed by UV-visible spectroscopy and appearance of new IR bands in the range of 934cm-1 to 1086cm-1 and shifting of N-C,S-S and S-C-S stretching, confirms the involvement of '-S-C-S-' group of methionine dithiocarbamate with GNPs. The presence of Au in MGNs was confirmed by EDXA spectrum, whereas TEM, SAED and XRD revealed that MGNs are nanocrystalline (~13nm) and have face-centered cubic structure. MGNs was labeled with 99mTc (TMGNs) with radiolabeling efficiency greater than 99% using 300μg of stannous chloride, pH 7 and 90.6 MBq of 99mTcO4. The stability data showed that the conjugate will remain infrangible in systemic circulation and in acidic microenvironment of tumor. The blood kinetic profile of TMGN in rabbits and biodistribution studies in EAT tumor bearing balb/c mice showed longer invivo circulation and slow clearance compared to radiolabeled methionine (TM). TMGN demonstrated nearly three-fold higher tumor accumulation (3.9±0.35% ID/g), 2-fold lower tumor saturation dose (1.0μg/kg) and higher tumor retention compared with TM. Data showed that the TMGN tumor: blood ratio (1.05) is nearly 2.5-fold higher than TM (0.44), whereas TMGN tumor: muscle ratio (97.5) is nearly 8-fold higher than TM (11.6). In conclusion, TMGN showed excellent tumor targeting and has promising prospects as a SPECT-radiopharmaceutical for imaging tumors.

Rationally assembled albumin/indocyanine green nanocomplex for enhanced tumor imaging to guide photothermal therapy

Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG–BSA nanocomplex (ICG–BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG–BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG–BSA NC treated group.

Manganese ion chelated FeOCl@PB@PDA@BPQDs nanocomposites as a tumor microenvironment-mediated nanoplatform for enhanced tumor imaging and therapy

Herein, a novel tumor microenvironment (TME)-mediated nanotheranostics platform of iron oxychloride (FeOCl) nanorods coated with Prussian Blue (PB), polydopamine (PDA), black phosphorus quantum dots (BPQDs) and chelated with Mn2+ was prepared. In the highly integrated nanoplatform (FeOCl@PB@PDA@BPQDs@Mn), FeOCl catalysts exhibit supreme efficiency to yield hydroxyl radicals (•OH) by H2O2 decomposition for chemodynamic therapy (CDT). Moreover, the PB, FeOCl, and Mn2+ have a catalase-like activity that catalyze H2O2 to release of O2 in the TME. Upon laser irradiation, the BPQDs transform O2 to a singlet oxygen (1O2) to self-enhance photodynamic therapy (PDT). Additionally, as a result of the high near-infrared (NIR) absorption rate and efficient photothermal conversion of PB and PDA, FeOCl@PB@PDA@BPQDs@Mn nanocomposites (NCs) are capable to work as ideal theranostic agents for photothermal therapy (PTT) in vitro and in vivo. Furthermore, FeOCl@PB@PDA@BPQDs@Mn NCs can also serve as multimodal imaging agents in different methods, such as magnetic resonance (MR), photoacoustic (PA), and ultrasound (US) imaging. Among the tumor models of mice, CDT, PDT, and PTT that combined with multimodal imaging achieved a more significant synergistic therapeutic result compared to any single treatment modality alone. Therefore, the multifunctional nanosystem in this study possesses tremendous potential in providing a satisfying paradigm for effective tumor treatment.