B-cell lymphoma with cytokine storm in serosal effusion: A case report and literature review.

RATIONALE: Cytokine storm is now considered to be a systemic inflammatory response, but local cytokine storm may exist in systemic diseases of the blood system. Monitoring of regional cytokine storm is an important clue for the diagnosis of systemic diseases. PATIENT CONCERNS: A 72-years-old male presented to our hospital with multiple serosal effusion without solid mass or enlarged lymph nodes. We found that the level of cytokines in ascites was tens to hundreds of times higher than that in plasma, mainly IL-6 and IL-8. DIAGNOSES: The patient was diagnosed with multiple serous effusion, hemophagocytic syndrome, B-cell lymphoma, Epstein-Barr virus infection, and hypoproteinemia. INTERVENTIONS: During hospitalization, the patient was treated with 5 courses of R-CVEP therapy and supportive treatment. OUTCOMES: After the first R-CVEP regimen, the patient's condition was evaluated as follows: hemophagocytic syndrome improved: no fever; Serum triglyceride 2.36 mmol/L; Ferritin 70.70 ng/L; no hemophagocyte was found in the bone marrow; the lymphoma was relieved, ascites disappeared, and bone marrow cytology showed: the bone marrow hyperplasia was reduced, and small platelet clusters were easily seen. Bone marrow flow cytometry showed that lymphocytes accounted for 13.7%, T cells increased for 85.7%, CD4/CD8 = 0.63, B cells decreased significantly for 0.27%, and NK cells accounted for 10.2%. Blood routine returned to normal: WBC 5.27 × 109/L, HB 128 g/L, PLT 129 × 109/L; Epstein-Barr virus DNA < 5.2E + 02 copies/mL; correction of hypoproteinemia: albumin 39.7 g/L. LESSONS: Cytokines in ascites are significantly higher than those in plasma by tens to hundreds of times, suggesting that "regional cytokine storms" may cause serosal effusion.

Whole-Exome Sequencing Reveals the Genomic Profile and IL6ST Variants as a Prognostic Biomarker of Paraneoplastic Pemphigus-Associated Unicentric Castleman Disease.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder. Paraneoplastic pemphigus (PNP) is a major complication associated with poor UCD prognosis. However, the genomic profiles and prognostic biomarkers of PNP-associated UCD remain unclear. In this study, we performed whole-exome sequencing analysis for 28 matched tumor-normal pairs and 9 tumor-only samples to define the genomic landscape of Chinese patients with PNP-associated UCD. An integrative analysis was performed to identify somatic variants, the mutational signatures, and key pathways in tumors. Besides, we analyzed the relationship among mutated genes, clinical characteristics, and prognosis. Sixty-one somatic mutant genes were identified in >1 patient with PNP-associated UCD. Specifically, IL6ST and PDGFRB were the most frequently mutated genes (32%), followed by DPP6 (18%) and MUC4 (18%). Signaling molecules and interactions, cellular processes, and signal transduction pathways were enriched. Furthermore, we found that poor overall survival was related to IL6ST variants (P = .02). Finally, we classified PNP-associated UCD into 4 genomic subgroups: IL6ST, PDGFRB, IL6ST-PDGFRB, and an unknown subgroup. In summary, we defined the molecular profile of PNP-associated UCD and identified a potential molecular biomarker for predicting prognosis, which may provide therapeutic targets for treating this severe disorder.

[Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism].

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1ß, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION: Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

[Establishment of a Patient-Derived T-Cell Acute Lymphoblastic Leukemia Xenograft Model in Novel Immunodeficient NCG Mice].

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.

Discovery of a novel water-soluble, rapid-release triptolide prodrug with improved drug-like properties and high efficacy in human acute myeloid leukemia.

In this work, a series of water-soluble triptolide prodrugs were synthesized, and their triptolide release rate, pharmacokinetic characteristics and anti-tumor effect were measured. We found that inserting glycolic acid as a linker between triptolide and the cyclic amino acid accelerated the release of triptolide from prodrugs into the plasma while preserving its safety. Among them, prodrug TP-P1 was significantly better than Minnelide (the only water-soluble triptolide prodrug in clinical trials) in terms of release rate in plasma and synthetic yield. In mouse models of human acute myeloid leukemia (AML), TP-P1 was effective in reducing xenograft tumors at dose levels as low as 25 µg/kg, and eliminating tumors at dose 100 µg/kg. Furthermore, TP-P1 could significantly enhance the efficacy of FLT3 inhibitors in the treatment of AML. These experimental results showed the potential of TP-P1 as water-soluble prodrugs of triptolide.

Paraneoplastic Pemphigus Autoantibodies Against C-terminus of Desmoplakin Induced Acantholysis In Vitro and In Vivo.

Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis in vivo in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin. In vitro dispase-dependent keratinocyte dissociation assay and in vivo IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (P-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.

Xanthan gum enhances peripheral blood CIK cells cytotoxicity in serum-free medium.

As a water-soluble macromolecule polysaccharide, xanthan gum (XG) has several biological activities, such as antitumor, antiviral, and immunomodulatory function. However, the effect of XG on the proliferation and cytotoxicity of cytokines induced killer (CIK) cells is rarely studied. In this study, the effect of XG on CIK cells derived from peripheral blood was investigated by analyzing the expansion fold of total cells, phenotype, cytotoxicity, degranulation, and apoptosis in serum-free medium. The results showed that the expansion fold of total cells with 100 µg/ml XG which molecule weight is 2.95 × 106 Da reached 4534.0 folds, significantly higher than that without XG (1299.0 folds, p < 0.05). The percentage of main effector cells-CD3+ CD56+ cells increased to 25.5% and the cytotoxic activity of CIK cells increased to 45.3%. The cell proportions of expression granzyme B and perforin that related to cytotoxicity in CIK cells reached 53.6% and 48.3%, respectively, significantly higher than 27.5% and 37.5% in the group without XG (p < 0.05). Collectively, XG could stimulate the ex vivo expansion of CIK cells and enhance the cytotoxicity of expanded CIK cells. The above results provide technical support for optimizing the expansion process of CIK cells ex vivo.

Continuous NF-κB pathway inhibition promotes expansion of human phenotypical hematopoietic stem/progenitor cells through metabolism regulation.

Hematopoietic stem/progenitor cells (HSPCs) ex vivo expansion is critical in facilitating their widespread clinical application. NF-κB pathway is implicated in the energy homeostasis and metabolic adaptation. To explore the effect of NF-κB pathway on the ex vivo HSPC expansion and metabolism, the 50 nM-1 µM inhibitor of NF-κB pathway TPCA-1 was used to expand cord blood derived CD34+ cells in serum-free culture. The expansion folds, function, mitochondrial profile and metabolism of HSPCs were determined. After 10 days of culture with 100 nM TPCA-1, the expansion of total cells， CD34+CD38- cells， and CD34+CD38-CD45RA-CD90+CD49f+ cells were significantly increased compared to the cytokine priming alone. Notably, TPCA-1 treatment generated ~ 2-fold greater percentage of CD34+EPCR+ and CD34+CD38-CD45RA-CD90+CD49f+ cells compared to cytokine only conditions. Moreover, TPCA-1 expanded CD34+ cells displayed enhanced serial colonies forming potential and secondary expansion capability. NF-κB inhibition increased the expression of self-renewal related genes, while downregulated the expression of mitochondrial biogenesis regulator (Pgc1α) and mitochondrial chaperones and proteases (ClpP, Hsp10, Hsp60). Mitochondrial mass and membrane potential were markedly decreased with TPCA-1 treatment, leading to the reduced mitochondrial reactive oxygen species (ROS) level in HSPCs. NF-κB inhibition displayed augmented glycolysis rate with compromising mitochondrial metabolism. This study demonstrated that NF-κB pathway inhibition improved glycolysis and limited ROS production that promoted the ex vivo expansion and maintenance of functional HSPCs.

Philadelphia chromosome-positive acute lymphoblastic leukemia: a case report.

Prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph-ALL) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT) is extremely poor. Therefore, effective alternative therapeutic measures are urgently needed. Recently, the use of antigen receptor-modified T cells holds great promise for relapsed and refractory ALL treatment. Prior to chimeric antigen receptor T-cell (CAR-T) infusion conditioning chemotherapy is used routinely to establish a favorable in vivo environment for CAR-T expansion, which has mostly involved fludarabine and cyclophosphamide. We report on a patient presented with extreme fatigue and anemia and was diagnosed with relapsed and refractory acute lymphoblastic leukemia (ALL) harbored T315I-BCR-ABL mutation, who had undergone allogeneic HSCT and multiple reinducing chemotherapy, but achieved complete hematologic remission (CHR) with CAR -T infusion as a later salvage treatment. Prior to CAR-T infusion there was no conditioning chemotherapy, but a bone marrow suppression period induced by ponatinib. CAR-T cell infusion was well tolerated and the patient achieved a CHR and maintained it for three months. At present, there is no relevant report on the use of tyrosine kinase inhibitors (TKI) as preconditioning protocols before CAR-T cells infusion. Our case indicated ponatinib not only reduces tumor burden but may also serve as a conditioning regimen for CAR-T therapy in the treatment of relapsed and refractory Ph-ALL.

Optimizing BIO feeding strategy promotes ex vivo expansion of human hematopoietic stem and progenitor cells.

Ex vivo expansion is critical in facilitating the application of hematopoietic/progenitor stem cells (HSPCs) for regenerative therapies. Wnt signaling is implicated in the expansion and self-renewal maintenance of HSPCs. However, a reasonable method to regulate Wnt signaling in ex vivo cultures to achieve robust expansion of HSPCs has not yet been investigated. Here, cord blood-derived CD34+ cells were cultured with the activator of Wnt signaling 6-bromoindirubin-3'-oxime (BIO) under the following conditions: vehicle control (group A); BIO was added to the culture on days 0, 4, and 7 (group B); and BIO was added to the culture on days 0 and 7 (group C). Initial BIO treatment promoted the expansion of CD34+ cells on day 4. However, BIO supplementation on days 0 and 4 in group B attenuated HSPC expansion on day 7, while enhancing the multilineage commit potential and secondary expansion ability of expanded CD34+ cells. Based on this finding, an optimized BIO feeding strategy (group C) was proposed to support substantial expansion of HSPCs. After 10 days of culture, the expansion fold of CD34+ cells was 28.70 ± 0.46-folds, which was significantly higher than group A (16.20 ± 0.72-folds, p < 0.05). Moreover, the optimized BIO feeding strategy achieved increased primitive HSPC expansion without the loss of biological functions. Mechanistically, the optimized BIO feeding strategy avoided the excessive activation of Wnt observed in group B while maintaining a moderate level of intracellular ß-catenin. These results provide an experimental and theoretical basis for Wnt regulation in ex vivo culture process and a potential strategy to expand HSPCs for transplantation.

Features and Risk Factors for Paraneoplastic Autoimmune Multiorgan Syndrome in 145 Chinese Patients.

Paraneoplastic autoimmune multiorgan syndrome is a complex and deadly disease. We retrospectively reviewed the clinical features and risk factors for paraneoplastic autoimmune multiorgan syndrome in 145 Chinese patients. The most common neoplasm was Castleman disease (56%), and patients with Castleman disease tended to be younger (≤ 42 years old: 83% vs. 29%) and to have a greater proportions of lichen planus-like lesions (47% vs. 27%) and bronchiolitis obliterans (49% vs. 29%), compared to other neoplasm-associated patients. Among all 145 patients in the study, the survival rates were 84% at 1 year, 65% at 3 years, and 54% at 5 years. Kaplan-Meier curve analysis revealed that mortality was associated with older age (> 42 years), neoplasm type, labial lesions, and larger skin lesion area (> 17.5% of the body surface area). However, only older age and larger skin lesion area were independent factors associated with mortality in multivariate analysis. We suggest that patients with Castleman disease and paraneoplastic autoimmune multiorgan syndrome have many unique characteristics and the underlying risk factors for death require further exploration.

[Curative Efficacy and Survival Analysis of Low-Intensity Traditional Chemotherapy Regimen in the Elderly Patients with Acute Myeloid Leukemia (non-M3)].

OBJECTIVE: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M3) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today. METHODS: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M3) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time. RESULTS: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection. CONCLUSION: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.

BIOCHIP mosaic for the diagnosis of autoimmune bullous diseases in Chinese patients.

BACKGROUND: Autoimmune blistering diseases (AIBDs) are a group of fatal diseases with specific autoantibodies. BIOCHIP mosaic is a novel and all-in-one measure used for the rapid diagnosis of AIBDs. OBJECTIVES: To evaluate the diagnostic accuracy based on BIOCHIP mosaic (FA1501-1005-60) in Chinese patients with AIBDs. MATERIALS AND METHODS: Seventy-seven patients with AIBDs and 20 controls were enrolled. The BIOCHIP mosaic was performed using both serum and plasma samples. RESULTS: Based on BIOCHIP mosaic, the data from paired plasma and serum samples demonstrated a high degree of concordance (Cohen's kappa = 0.896-1.000) for autoantibodies against Dsg1, Dsg3, BP180-NC16A-4X, BP230gC, prickle-cell desmosomes, and pemphigoid antigens. Moreover, BIOCHIP mosaic also demonstrated a high degree of consistency for the detection rate of anti-Dsg1, Dsg3, plakins, BP180-NC16A-4X and non-collagenous domain of type VII collagen autoantibodies for the diagnosis of pemphigus foliaceus (77.3%), pemphigus vulgaris (88.6%), paraneoplastic pemphigus (100.0%), bullous pemphigoid (92.8%) and epidermolysis bullosa acquisita (99.0%), respectively. CONCLUSION: Using BIOCHIP mosaic, serum and plasma samples may be used interchangeably at 1/10 dilution. Overall, the BIOCHIP mosaic was shown to be a useful and accurate tool for the diagnosis of AIBDs.

A novel methodology of the myeloid-derived suppressor cells (MDSCs) generation with splenic stroma feeder cells.

Myeloid-derived suppressor cells (MDSCs) are a significant obstacle for immunotherapy of cancer. It is of great clinical relevance to study the mechanism of MDSCs accumulation in mouse spleens and establish a stable method to obtain high-purity MDSCs in vitro for further research. Here, we established a new method for amplifying a large number of highly pure MDSCs in vitro. To mimic the microenvironment of MDSCs development in vivo, mouse splenic stroma feeder cells and serum-free medium containing granulocyte-macrophage colony stimulating factor (GM-CSF) were used to induce myeloid precursors in mouse bone marrow cells, which differentiate into MDSCs. Development and immunological functions of the cells were monitored both in vivo and in vitro. A total of 4 × 108 MDSCs could be obtained from the bone marrow from one mouse, the ratio of CD11b+Gr-1+ MDSCs could reach 93.8% ± 3.3% after nine days of culture in vitro. Cultured MDSCs maintained a similar immunophenotype with MDSCs found in tumor-bearing mice. Colony forming assay in vitro and in vivo demonstrated that these were myeloid precursor cells. These cells generated high levels of reactive oxygen species and arginase 1 to prevent proliferation of CD8+ T cells in vitro. These also increased regulatory T (Treg) cells in blood while promoting the growth of lymphoma in vivo. In addition, cultured MDSCs effectively inhibited acute graft-versus-host disease (aGVHD). Our findings suggest that mouse splenic stroma plays an important role in the generation of MDSCs and represent a preliminary mechanism for the accumulation of MDSCs in spleens, and thereby lay the foundation for basic research and the clinical application of MDSCs.

Predominant Stroma-Rich Feature in Hyaline Vascular Variant of Castleman Disease Is Associated With Paraneoplastic Pemphigus.

OBJECTIVES: We aimed to describe the clinical and histopathologic features of Castleman disease (CD), particularly emphasizing its associations with paraneoplastic pemphigus (PNP) and prognosis. METHODS: We retrospectively enrolled 123 CD patients at our center. Clinical, pathologic, and laboratory data were reviewed. RESULTS: Fifty percent of the patients had PNP. Compared with those without PNP, patients with PNP-associated CD had more hyaline vascular (HV) variants (83.9% vs 57.4%), fewer mixed cellular variants (16.1% vs 24.6%), and no plasmacytic variants (0% vs 18.0%). Thirty-eight of 87 patients with the HV variant of CD (HV-CD) had stroma-rich (SR) features, and the incidence rate was higher in those with PNP-associated CD than in those without PNP (48.4% vs 13.1%, P < .001). The SR variant was associated with higher PNP-associated IgG titers than SR absence before surgery (median 1:160 vs 1:80, P = .019) or after surgery (median 1:160 vs 1:40, P = .013). The SR variant was also an unfavorable prognostic factor for CD survival in univariate analysis. The 3-year survival rates were 47.5% among those with PNP and 87.7% among those without PNP (P < .001). CONCLUSIONS: PNP is associated with specific subtypes of CD and affects survival. The SR variant of HV-CD positively correlates with the incidence of PNP.

Solasonine Suppresses the Proliferation of Acute Monocytic Leukemia Through the Activation of the AMPK/FOXO3A Axis.

Solasonine, the main active ingredient of Solanum nigrum L., has been reported to exert extensive antitumor activity. However, the antitumor effects in acute monocytic leukemia and the exact mechanisms involved are unknown. In this study, we investigated the role of solasonine on inhibiting the progression of acute monocytic leukemia. Our findings showed that solasonine inhibited the proliferation of acute monocytic leukemic cell lines (THP-1 and MV4-11) in vitro. Solasonine promoted apoptosis and induced cell cycle arrest in the G2/M phase. Analysis of RNA-seq data suggested that solasonine correlated with increased expression of genes in the AMPK/FOXO3A pathway. Inhibition of AMPK with compound C followed by treatment with solasonine showed that solasonine reduced apoptosis, caused less cell cycle arrest, and inactivated the AMPK/FOXO3A axis in THP-1 and MV4-11 cells. Solasonine also inhibited tumor growth by the activation of the AMPK/FOXO3A axis. In conclusion, solasonine inhibited the progress of acute monocytic leukemia in vitro and in vivo and triggered the apoptosis and cell cycle arrest in the G2/M phase by upregulating the AMPK/FOXO3A pathway.

Zwitterionic Conjugated Polymer as the Single Component for Photoacoustic-Imaging-Guided Dual-Modal Near-Infrared Phototherapy.

Systems consisting of different functional components that synergistically increase the antitumor efficiency of different cancer therapies are in great demand. Here, we report the use of nanoparticles (NPs) composed of a zwitterionic conjugated polymer, generating reactive oxygen species (ROS) and heat. These NPs are more effective in antitumor than single photodynamic therapy (PDT) or photothermal therapy (PTT) and have an optimal absorbance ranging from 700 to 850 nm. Light in this range is capable of reaching tumors by penetrating deep into tissues. The simultaneous PDT and PTT using a single near-infrared (NIR) light can be monitored via photoacoustic imaging (PAI). Treatment of tumor-bearing nude mice with combined PDT and PTT following tail vein injection of NPs resulted in complete tumor remission. No tumor relapse was observed during a 20 day treatment. These zwitterionic conjugated polymeric NPs with the capability of generating ROS and heat show great potential for PAI-guided photodynamic/photothermal dual-modal therapy.