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2.
Bioconjug Chem ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31880916

RESUMO

In this study, we applied a new strategy to identify sentinel lymph node (SLN) metastasis by combining 68Ga-NOTA-Evans Blue (68Ga-NEB) for SLN mapping and 68Ga-NOTA-RM26 for LN metastasis detection in breast cancer patients. A total of 24 female patients with breast cancer diagnosed by core biopsy or suspected by mammography or ultrasonography were recruited and provided informed consent. All patients underwent 68Ga-NEB and 68Ga-NOTA-RM26 PET/CT imaging. Visual analysis of 68Ga-NEB PET/CT images was used to determine SLNs, and then compared with the 68Ga-NOTA-RM26 results and histopathological findings. SLNs were visualized in 24 of 24 patients (100.0%) within 4.0-10.0 (5.6 ± 1.4) min. All patients were pathologically diagnosed with breast cancer, and 12 patients had ipsilateral lymph node metastasis. By combining 68Ga-NEB and 68Ga-NOTA-RM26 images, 7/12 (58.3%) patients showed mild to intense uptake of 68Ga-NOTA-RM26 in SLNs, 1/12 patient (8.3%) had moderate uptake of 68Ga-NOTA-RM26 in the non-SLNs rather than SLN, indicating possible bypass lymphatic drainage, partially accounting for the false negatives in SLN biopsy during surgery. No false positives were found. The SUVmax of 68Ga-NOTA-RM26 activity in metastatic SLNs was significantly higher than that in non-metastatic SLNs (2.2 ± 2.3 vs 0.7 ± 0.1, P = 0.047). This study manifests the value of combination of 68Ga-NEB and 68Ga-NOTA-RM26 dual tracer PET/CT in preoperative evaluation of SLN metastasis in breast cancer patients, especially in those patients with lymphatic obstruction and bypass drainage. In general, positive 68Ga-NOTA-RM26 uptake in either SLN or other lymph nodes can apply lymph node dissection rather than intraoperative SLN biopsy.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31832728

RESUMO

PURPOSE: To evaluate the safety and efficacy of 177Lu-DOTA-EB-TATE, a radiolabeled somatostatin analog modified by Evans blue, at escalating doses, was used to increase tumor retention in patients with progressive metastatic neuroendocrine tumors (NETs). METHODS: Thirty-three patients with metastatic NETs were prospectively enrolled into four groups: group A (n = 6, 43 ± 12 years) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTATATE as controls; group B (n = 7, 55 ± 7 years) administered approximately 1.11 GBq (30 mCi) 177Lu-DOTA-EB-TATE; group C (n = 6, 55 ± 10 years) administered approximately 1.85 GBq (50 mCi) 177Lu-DOTA-EB-TATE; group D (n = 14, 50 ± 10 years) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTA-EB-TATE. Treatment-related adverse events were graded according to the CTCAE v.5.0. 68Ga-DOTATATE PET/CT were performed at baseline and 2-3 months after treatment for response evaluation. RESULTS: Administration was well tolerated. No CTC 3/4 hematotoxicity, nephrotoxicity, or hepatotoxicity was observed during or after treatment in groups A-C. In group D, CTC-3 hematotoxicity was recorded in 2 patients with multicourse chemotherapy previously. After one-cycle treatment, the SUVmax decreased in group C (Δ% = - 17.4 ± 29.3%) and group D (Δ% = - 15.1 ± 39.1%), but greatly increased in group B (Δ% = 30.0 ± 68.0%) and mildly increased in group A (Δ% = 5.4 ± 45.9%). Referring to EORTC criteria, 16.7% (1/6), 0% (0/7), 50% (3/6), and 50% (7/14) were evaluated as partial response in groups A, B, C, and D, respectively. When selecting lesions with comparable baseline SUVmax ranging from 15 to 40, SUVmax showed no significant decrease in group B (Δ% = - 7.3 ± 24.5%) (P = 0.214), significant decrease in group C (Δ% = - 34.9 ± 12.4%) (P = 0.001), and in group D (Δ% = - 17.9 ± 19.7%) (P = 0.012) as compared with group A with increased SUVmax (Δ% = 8.4 ± 48.8%). SUVmax significantly decreased in the EBTATE groups (groups B-D combined) (Δ% = - 19.0 ± 21.5%) as compared with the TATE group (P = 0.045). CONCLUSION: 177Lu-DOTA-EB-TATE is well tolerated and is more effective than 177Lu-DOTATATE. Both 1.85 GBq (50 mCi) and 3.7 GBq (100 mCi) doses appear to be more effective than 1.11 GBq (30 mCi) dose. Further investigation with more cycles of 177Lu-DOTA-EB-TATE treatment and longer follow-up is warranted. TRIAL REGISTRATION: Treatment Using 177Lu-DOTA-EB-TATE in Patients with Advanced Neuroendocrine Tumors (NCT03478358). URL: https://register.clinicaltrials.gov/prs/app/action/ViewOrUnrelease?uid=U0001JRW&ts=13&sid=S0007RNX&cx=y3yqv4.

4.
Nano Lett ; 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31838855

RESUMO

Molecular probes featuring promising capabilities including specific targeting, high signal-to-noise ratio, and in situ visualization of deep tissues are in great demand for tumor diagnosis and therapy. 19F magnetic resonance imaging (MRI) techniques incorporating stimuli-responsive probes are anticipated to be highly beneficial for specific detection and imaging of tumor because of negligible background and deep tissue penetration. Herein, we report a cascaded multiresponsive self-assembled nanoprobe, which enables sequential redox-triggered and near infrared (NIR) irradiation-induced 19F MR signal activation/amplification for sensing and imaging. Specifically, we designed and synthesized a cascaded multiresponsive 19F-bearing nanoprobe based on the self-assembly of amphiphilic redox-responsive 19F-containing polymers and NIR-absorbing indocyanine green (ICG) molecules. It could realize the activation of 19F signals in reducing tumor microenvironment and subsequent signal amplification via photothermal process. This stepwise two-stage activation/amplification of 19F signals was validated by 19F NMR and MRI both in vitro and in vivo. The multiresponsive 19F nanoprobes capable of cascaded 19F signal activation/amplification and photothermal effect exertion can provide accurate sensing and imaging of tumor.

5.
J Am Chem Soc ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31823608

RESUMO

Multinuclear complexes as metallo-agents for clinical use have caught extensive attention. In this paper, using DOTA as both a functioning unit and a constructing junction, we build a series of DOTA-branched organic frameworks (DBOF) with multiple chelating holes by organizing DOTA layer by layer. These giant chelators are well characterized, which re-veals their nano-sized and soft structures. Further experiments demonstrate that they could efficiently hold abundant metal ions with much higher kinetic stabilities than the conventional small DOTA chelator. Their corresponding polynu-clear complexes containing Gd3+, Tb3+, or both show superior imaging properties, excellent feasibility for peripheral modi-fication, and unusual kinetic stability. This work can be easily extended to the fabrication of diverse homo-multinuclear complexes and core/shell hetero-multinuclear complexes with multifunctional properties. We expect that this new type of giant molecules and the ligand-branching strategy would open up a new avenue for the design and construction of next-generation polymetallic agents with high performance and stabilities for biomedical applications.

6.
J Nucl Med ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31806769

RESUMO

Objectives: The detection of cancer micrometastasis for early diagnosis and treatment poses a great challenge for conventional imaging techniques. The aim of study is to evaluate the performance of photoacoustic imaging (PAI) in detecting hepatic micrometastases from melanoma in a very early stage and perform tumor resection by intraoperative photoacoustic image-guidance. Methods: In vivo studies were performed by following protocols approved by the Ethical Committee for Animal Research at Xiamen University. First, a B16 melanoma hepatic metastasis mouse model (n = 10) was established to study the development of micrometastases in vivo. Next, the hepatic metastasis mice models were imaged by scalable PAI instrument, ultrasound, 9.4 T high-resolution magnetic resonance imaging (MRI), positron emission tomography/computed tomography (PET/CT), and bioluminescence imaging. Photoacoustic images acquired with optical wavelengths spanning from 680 to 850 nm were spectrally unmixed by using a linear least-squares method to differentiate various components. Differences in the signal-to-background ratios among different modalities were determined with the two-tailed paired t test. The diagnosis results were assessed with histologic examinations. Excised liver samples from patients diagnosed with hepatic cancer were also examined to identify tumor boundary. In vivo metastatic melanoma removal in surgery was precisely guided by the portable PAI system. Results: PAI achieved as small as ~400 µm hepatic melanoma detection at a depth up to 7 mm in vivo, which could early detect small melanoma compared with ultrasound and MRI in mouse models. The signal ratio of tumor-to-liver acquired with PAI in micrometastases at 8 days (4.2 ± 0.2, n = 6) and 14 days (9.2 ± 0.4, n = 5) were significantly higher than those obtained with PET/CT (1.8 ± 0.1, n = 5 and 4.5 ± 0.2, n = 5, P <0.001 for both). Functional PAI provided dynamic oxygen saturation changes during tumor growth. The limit of detection was measured to be approximately 219 cells per microliter in vitro. We successfully performed intraoperative photoacoustic image-guided surgery in vivo using the rapid portable PAI system. Conclusion: Our findings offer a rapid and effective tool to noninvasively detect micrometastases and guide intraoperative resection as a complementary clinical imaging application.

7.
ACS Nano ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31877023

RESUMO

Combination therapy that could better balance immune activation and suppressive signals holds great potential in cancer immunotherapy. Herein, we serendipitously found that the pH-responsive nanovesicles (pRNVs) self-assembled from block copolymer polyethylene glycol-b-cationic polypeptide can not only serve as a nanocarrier but also cause immunogenic cell death (ICD) through preapoptotic exposure of calreticulin. After coencapsulation of a photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) and an indoleamine 2,3-dioxygenase inhibitor, indoximod (IND), pRNVs/HPPH/IND at a single low dose elicited significant antitumor efficacy and abscopal effect following laser irradiation in a B16F10 melanoma tumor model. Treatment efficacy attributes to three key factors: (i) singlet oxygen generation by HPPH-mediated photodynamic therapy (PDT); (ii) increased dendritic cell (DC) recruitment and immune response provocation after ICD induced by pRNVs and PDT; and (iii) tumor microenvironment modulation by IND via enhancing P-S6K phosphorylation for CD8+ T cell development. This study exploited the nanocarrier to induce ICD for the host's immunity activation. The "all-in-one" smart nanovesicles allow the design of multifunctional materials to strengthen cancer immunotherapy efficacy.

8.
ACS Nano ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869210

RESUMO

Magnetic targeting strategies employ external magnet fields to manipulate magnetic nanoparticles (MNPs) remotely, aiming to enhance their accumulation and penetration in vivo, which have received increasing attention in drug-delivery systems over the past decades. However, this approach has not yet been successful in translational clinical studies, largely due to the low efficacy and uncontrollable distribution of MNPs. The standard magnetic targeting strategy uses a single magnet and, thus, suffers from rapid drop-off of the magnetic field and field gradient with increasing distance away from the magnet surface. As a result, magnetic targeting of MNPs is often limited to superficial regions of interest. As reported in this issue of ACS Nano, Andrew Tsourkas and his colleagues showed that a two-magnet configuration can solve this dilemma by introducing a constant field gradient between the magnets for advanced magnetic targeting. The custom-built two-magnet device evidenced greatly enhanced accumulation and penetration of MNPs in a solid tumor model, shedding new light on future design considerations of magnetic targeting systems.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31710266

RESUMO

Background: Despite advances in surgical techniques and peri-operative management, post-operative infectious complications still are common after perihilar cholangiocarcinoma (PHCC). This study investigated the predictive factors and microbial spectrum for infections after hepatectomy with cholangiojejunostomy performed to treat PHCC. Methods: A total of 70 consecutive patients, who underwent hepatectomy with cholangiojejunostomy by the same surgeons at a tertiary referral medical center between September 2010 and January 2019, were enrolled. Clinical data were reviewed for multivariable analysis to find independent risk factors for infectious complications. Microorganisms isolated from bile and infection sites were counted to explore the microbial spectrum. Results: A total of 43 patients (61.4%) suffered post-operative infections (33 with surgical site infection [SSI], four with bacteremia, three with pneumonia, 10 with cholangitis, and two with fungus infectious stomatitis), and 28 of them (65.1%) had a positive bile culture. Four independent risk factors were identified: male sex (odds ratio [OR] 12.737; 95% confidence interval [CI] 2.298-70.611; p = 0.004), red blood cell (RBC) count <3.8 × 1012/L (OR 5.085; 95% CI 1.279-20.211; p = 0.021), total cholesterol (TC) <2.90 mmol/L (OR 5.715; 95% CI 1.534-21.299; p = 0.009), and serum Na+ >145 mmol/L (OR 10.387; 95% CI 1.559-69.201; p = 0.016) on post-operative day (POD) 1. A total of 217 and 196 microorganisms were cultured from 311 and 627 specimens, respectively, collected from pre-/intra-operative bile and possible infection sites. Staphylococcus, Enterococcus, Acinetobacter, Streptococcus, and Escherichia were the most common findings of bile culture. The first five organisms most frequently isolated from infection sites were Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, and Candida. A total of 18 patients (64.3%) had at least one species isolated from infection sites that had appeared in a previous bile culture. Conclusions: Male sex, erythrocytopenia, hypocholesterolemia, and hypernatremia on POD 1 are independent risk factors for infectious complications. For patients without positive bile cultures, third-generation cephalosporins could be considered as the prophylactic antibiotic. It is important to monitor the pathogens throughout the hospital stay.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31710768

RESUMO

Sonodynamic therapy (SDT) has the advantages of high penetration, non-invasiveness, and controllability, and it is suitable for deep-seated tumors. However, there is still a lack of effective sonosensitizers with high sensitivity, safety, and penetration. Now, ultrasound (US) and glutathione (GSH) dual responsive vesicles of Janus Au-MnO nanoparticles (JNPs) were coated with PEG and a ROS-sensitive polymer. Upon US irradiation, the vesicles were disassembled into small Janus Au-MnO nanoparticles (NPs) with promoted penetration ability. Subsequently, GSH-triggered MnO degradation simultaneously released smaller Au NPs as numerous cavitation nucleation sites and Mn2+ for chemodynamic therapy (CDT), resulting in enhanced reactive oxygen species (ROS) generation. This also allowed dual-modality photoacoustic imaging in the second near-infrared (NIR) window and T1 -MR imaging due to the released Mn2+ , and inhibited orthotopic liver tumor growth via synergistic SDT/CDT.

11.
Theranostics ; 9(24): 7200-7209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695762

RESUMO

Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death. Methods: A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO2 NPs) was presented, which simultaneously delivered exogenous H2O2 and Zn2+ capable of amplifying endogenous ROS production for synergistic cancer therapy. Results: After internalization into tumor cells, ZnO2 NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H2O2 and Zn2+. Intriguingly, Zn2+ could increase the production of mitochondrial O2·- and H2O2 by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H2O2 to promote cancer cell killing. Furthermore, ZnO2 NPs were doped with manganese via cation exchange, making them an activatable magnetic resonance imaging contrast agent. Conclusion: This study establishes a ZnO2-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.

12.
Theranostics ; 9(24): 7210-7221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695763

RESUMO

Suspension arrays based on optical encoded microspheres have attracted great attention for multiplexed detection in gene analysis, protein profiling, early disease diagnosis, treatment monitoring and so on. However, the fluorescence stability of barcodes and detection sensitivity require further improvement to meet the increasing demands of "precision diagnosis". Methods: This work reports a novel suspension array platform based on extremely stable AIEgens (AIE33 and AIE NIR800) microbeads as barcodes and AIEgens (1,1,2,3,4,5-Hexaphenyl-1H-silole, HPS) nanobeads as fluorescent signal reporter coupled with flow cytometry for multiplexed detection. Results: Due to the excellent fluorescent signal amplification effect of the HPS nanobeads, our multiplex assay showed enhanced detection sensitivity, compared to multiplex assay using QDs nanobeads (up to 3-fold improvement) and commercial organic dye of phycoerythrin (up to 5-fold improvement) as the fluorescent signal reporters. Conclusion: Furthermore, validating experiments showed similar detection performance to the clinical gold-standard method of ImmunoCAP for allergen detection in patient serum samples, demonstrating the suspension array platform based on AIEgens microbeads with excellent fluorescence stability and AIEgens nanobeads with strong signal amplification ability is promising for high-sensitivity multiplexed bioassay applications.

13.
Theranostics ; 9(25): 7948-7960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695808

RESUMO

RATIONALE: Radiotherapy combined with immunotherapy has revealed promising outcomes in both preclinical studies and ongoing clinical trials. Targeted radionuclide therapy (TRT) is a branch of radiotherapy concerned with the use of radioisotopes, radiolabeled molecules or nanoparticles that deliver particulate radiation to cancer cells. TRT is a promising approach in cases of metastatic disease where conventional treatments are no longer effective. The increasing use of TRT raises the question of how to best integrate TRT with immunotherapy. In this study, we proposed a novel therapeutic regimen that combined programmed death ligand 1 (PD-L1)-based immunotherapy with peptide-based TRT (177Lu as the radionuclide) in the murine colon cancer model. METHODS: To explore the most appropriate timing of immunotherapy after radionuclide therapy, the anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner when 177Lu TRT was given. RESULTS: The results demonstrated that TRT led to an acute increase in PD-L1 expression on T cells, and TRT in combination with αPD-L1 mAb stimulated the infiltration of CD8+ T cells, which improved local tumor control, overall survival and protection against tumor rechallenge. Moreover, our data revealed that the time window for this combination therapy may be critical to outcome. CONCLUSIONS: This therapeutic combination may be a promising approach to treating metastatic tumors in which TRT can be used. Clinical translation of the result would suggest that concurrent rather than sequential blockade of the PD-1/PD-L1 axis combined with TRT improves overall survival and long-term tumor control.

14.
Small ; : e1903861, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31736250

RESUMO

Herein, a smart supramolecular self-assembly-mediated signal amplification strategy is developed on a paper-based nanobiosensor to achieve the sensitive and customized detection of biomarkers. The host-guest recognition between ß-cyclodextrin-coated gold nanoparticles (AuNPs) and 1-adamantane acetic acid or tetrakis(4-carboxyphenyl)porphyrin is designed and applied to the layer-by-layer self-assembly of AuNPs at the test area of the strip. Thus, the amplified platform exhibits a high sensitivity with a detection limit at subattogram levels (approximately dozens of molecules per strip) and a wide dynamic range of concentration over seven orders of magnitude. The applicability and universality of this sensitive platform are demonstrated in clinically significant ranges to measure carcinoembryonic antigen and HIV-1 capsid p24 antigen in spiked serum and clinical samples. The customized biomarker detection ability for the on-demand needs of clinicians is further verified through cycle incubation-mediated controllable self-assembly. Collectively, the supramolecular self-assembly amplification method is suitable as a universal point-of-care diagnostic tool and can be readily adapted as a platform technology for the sensitive assay of many different target analytes.

16.
ACS Appl Mater Interfaces ; 11(41): 37461-37470, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31577423

RESUMO

An important objective of cancer nanomedicine is to improve the delivery efficacy of functional agents to solid tumors for effective cancer imaging and therapy. Stimulus-responsive nanoplatforms can target and regulate the tumor microenvironment (TME) for the optimization of cancer theranostics. Here, we developed magnetic manganese oxide sweetgum-ball nanospheres (MMOSs) with large mesopores as tools for improved cancer theranostics. MMOSs contain magnetic iron oxide nanoparticles and mesoporous manganese oxide (MnO2) nanosheets, which are assembled into gumball-like structures on magnetic iron oxides. The large mesopores of MMOSs are suited for cargo loading with chlorin e6 (Ce6) and doxorubicin (DOX), thus producing so-called CD@MMOSs. The core of magnetic iron oxides could achieve magnetic targeting of tumors under a magnetic field (0.25 mT), and the targeted CD@MMOSs may decompose under TME conditions, thereby releasing loaded cargo molecules and reacting with endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) and manganese (II) ions (Mn2+). Investigation in vivo in tumor-bearing mice models showed that the CD@MMOS nanoplatforms achieved TME-responsive cargo release, which might be applied in chemotherapy and photodynamic therapy. A remarkable in vivo synergy of diagnostic and therapeutic functionalities was achieved by the decomposition of CD@MMOSs and coadministration with chemo-photodynamic therapy of tumors using the magnetic targeting mechanism. Thus, the result of this study demonstrates the feasibility of smart nanotheranostics to achieve tumor-specific enhanced combination therapy.

17.
Nanoscale Horiz ; 4(2): 426-433, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31565239

RESUMO

A Pt prodrug polyphenol and gadolinium ion loaded cancer theranostics nanoplatform based on mild acidic pH and thermal sensitive polymer was designed for photoacoustic (PA)/ magnetic resonance(MR)/ positron emission tomography (PET) multimodal imaging-guided chemo-photothermal combination therapy. The Pt drug release can be controlled by tumour-specific acidic pH and heat generated by external NIR irradiation. The nanoparticles were stable under normal physiological environment and released the drug under tumour acidic pH and NIR laser irradiation, which can reduce the side effect of drug to normal organs. Moreover, the MR signal can be significantly enhanced (~3-fold increase in T1 relaxivity) under the acidic tumour microenvironment, which is favorable for cancer diagnosis. The nanoparticles exhibited excellent tumour accumulation and led to complete tumour eradication with low power NIR laser irradiation. This promising approach provides a new avenue for imaging-guided combination therapy.

18.
Bioconjug Chem ; 30(11): 2870-2878, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31593447

RESUMO

Boronophenylalanine (BPA) is the dominant boron delivery agent for boron neutron capture therapy (BNCT), and [18F]FBPA has been developed to assist the treatment planning for BPA-BNCT. However, the clinical application of BNCT has been limited by its inadequate tumor specificity due to the metabolic instability. In addition, the distinctive molecular structures between [18F]FBPA and BPA can be of concern as [18F]FBPA cannot quantitate boron concentration of BPA in a real-time manner. In this study, a metabolically stable boron-derived tyrosine (denoted as fluoroboronotyrosine, FBY) was developed as a theranostic agent for both boron delivery and cancer diagnosis, leading to PET imaging-guided BNCT of cancer. [18F]FBY was synthesized in high radiochemical yield (50%) and high radiochemical purity (98%). FBY showed high similarity with natural tyrosine. As shown in in vitro assays, the uptake of FBY in murine melanoma B16-F10 cells was L-type amino acid transporter (LAT-1) dependent and reached up to 128 µg/106 cells. FBY displayed high stability in PBS solution. [18F]FBY PET showed up to 6 %ID/g in B16-F10 tumor and notably low normal tissue uptake (tumor/muscle = 3.16 ± 0.48; tumor/blood = 3.13 ± 0.50; tumor/brain = 14.25 ± 1.54). Moreover, administration of [18F]FBY tracer along with a therapeutic dose of FBY showed high accumulation in B16-F10 tumor and low normal tissue uptake. Correlation between PET-image and boron biodistribution was established, indicating the possibility of estimating boron concentration via a noninvasive approach. At last, with thermal neutron irradiation, B16-F10 tumor-bearing mice injected with FBY showed significantly prolonged median survival without exhibiting obvious systemic toxicity. In conclusion, FBY holds great potential as an efficient theranostic agent for imaging-guided BNCT by offering a possible solution of measuring local boron concentration through PET imaging.

19.
J Mater Chem B ; 7(37): 5688-5694, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31475276

RESUMO

Combination therapy with multiple chemotherapeutic agents is the main approach for cancer treatment in the clinic. Polyphenol-based materials are found in our diet, demonstrate good biocompatibility, and prevent numerous diseases. In this study, we encapsulate two drugs in a single polyphenol-based polymer with Fe3+ or Mn2+ ions as the cross-linker for cancer therapy. The combination index of two drugs is an essential parameter to evaluate drug combinations. The amphiphilic polymer poly(ethylene glycol)-block-polydopamine (PEG-PDA) was prepared by RAFT polymerization. The nanoparticles were prepared via self-assembly with Fe3+ or Mn2+ ions. Both doxorubicin (DOX) and simvastatin (SV) were encapsulated in the core of the nanoparticles. The cell viability and combination index were evaluated in vitro. The tumor accumulation of the nanoparticles was investigated by positron-emission tomography (PET) and magnetic resonance (MR) imaging. The as-prepared nanoparticles exhibited high drug loading capacity. The drug loaded nanoparticles could kill cancer cells effectively with a combination index <1. Both PET and MRI revealed that the nanoparticles showed long blood circulation time and high tumor accumulation. The nanoparticles could inhibit tumor inhibition via intravenous injection of nanoparticles. The polyphenol-based nanoplatform may serve as a promising theranostic candidate for clinical application.

20.
Adv Mater ; 31(49): e1904329, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31538379

RESUMO

Surgical resection is the primary and most effective treatment for most patients with solid tumors. However, patients suffer from postoperative recurrence and metastasis. In the past years, emerging nanotechnology has led the way to minimally invasive, precision and intelligent oncological surgery after the rapid development of minimally invasive surgical technology. Advanced nanotechnology in the construction of nanomaterials (NMs) for precision imaging-guided surgery (IGS) as well as surgery-assisted synergistic therapy is summarized, thereby unlocking the advantages of nanotechnology in multimodal IGS-assisted precision synergistic cancer therapy. First, mechanisms and principles of NMs to surgical targets are briefly introduced. Multimodal imaging based on molecular imaging technologies provides a practical method to achieve intraoperative visualization with high resolution and deep tissue penetration. Moreover, multifunctional NMs synergize surgery with adjuvant therapy (e.g., chemotherapy, immunotherapy, phototherapy) to eliminate residual lesions. Finally, key issues in the development of ideal theranostic NMs associated with surgical applications and challenges of clinical transformation are discussed to push forward further development of NMs for multimodal IGS-assisted precision synergistic cancer therapy.

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