19 research outputs found
Activatable Ferritin Nanocomplex for Real-Time Monitoring of Caspase‑3 Activation during Photodynamic Therapy
One mechanism of photodynamic therapy
(PDT) for the ablation of tumors is to induce apoptosis. Visualization
of apoptosis during PDT in real-time is of great benefit for predicting
and evaluating therapeutic outcomes. Herein, we engineered a highly
stable and sensitive caspase-3 ferritin activatable probe (FABP/ZnPc)
for simultaneous delivery of a photosensitizer (ZnPc) and real-time
visualization of apoptosis during PDT. Upon near-infrared (NIR) light
irradiation, ZnPc becomes active and initiates apoptosis, upon which
the outer layer of the FABP/ZnPc is degraded by the apoptotic marker,
caspase-3, to boost strong fluorescent signals, ultimately allowing
real-time imaging of apoptosis. Our results demonstrate the utility
of FABP/ZnPc as a tool for PDT and simultaneous imaging of caspase-3
activation in vitro and in vivo. Overall, the ability of FABP/ZnPc
to image apoptosis during PDT will not only facilitate optimizing
and personalizing the PDT strategy but is also important for understanding
the mechanisms of PDT
Activatable Hyaluronic Acid Nanoparticle as a Theranostic Agent for Optical/Photoacoustic Image-Guided Photothermal Therapy
Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5–HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25 ± 0.25 for optical imaging and 3.8 ± 0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics
Synthesis and Preliminary Study of <sup>99m</sup>Tc-Labeled HYNIC-FAPi for Imaging of Fibroblast Activation Proteins in Tumors
Fibroblast
activation protein (FAP) is an emerging target for cancer
diagnosis. Different types of FAP inhibitor (FAPI)-based radiotracers
have been developed and applied for tumor imaging. However, few FAPI
tracers for single photon emission computed tomography (SPECT) imaging
have been reported. SPECT imaging is less expensive and more widely
distributed than positron emission tomography (PET), and thus, 99mTc-labeled FAPIs would be more available to patients in
developing regions. Herein, we developed a FAPI-04-derived radiotracer,
HYNIC-FAPi-04 (HFAPi), for SPECT imaging. 99mTc-HFAPi,
with a radiochemical purity of >98%, was prepared using a kit formula
within 30 min. The specificity of 99mTc-HFAPi for FAP was
validated by a cell binding assay in vitro and SPECT/CT imaging in vivo.
The binding affinity (Kd value) of 99mTc-HFAPi for human FAP and murine FAP was 4.49 and 2.07
nmol/L, respectively. SPECT/CT imaging in HT1080-hFAP tumor-bearing
mice showed the specific FAP targeting ability of 99mTc-HFAPi in vivo. In U87MG tumor-bearing mice, 99mTc-HFAPi had a higher tumor uptake compared with that of
HT1080-hFAP and 4T1-mFAP tumor models. Interestingly, 99mTc-HFAPi showed a relatively high uptake in some murine joints. 99mTc-HFAPi accumulated in tumor lesions with a high tumor-to-background
ratio. A preliminary clinical study was also performed in breast cancer
patients. Additionally, 99mTc-HFAPi exhibited an advantage
over 18F-FDG in the detection of lymph node metastatic
lesions in breast cancer patients, which is helpful in improving treatment
strategies. In short, 99mTc-HFAPi showed excellent affinity
and specificity for FAP and is a promising SPECT radiotracer for (re)staging
and treatment planning of breast cancers
Nucleophilic Degradation of Chemical Warfare Agents Using Nonaqueous Decontamination Formula
The degradation or removal of chemical,
biological, and radioactive
contaminants is a supporting technique for homeland defense and countering
terrorism. A highly efficient, noncorrosive, nonaqueous formula based
on alkali, alcohol, and amine was developed for degradation of chemical
warfare agents (CWAs). The optimized formula consisted of 50% ethanolamine,
9% benzyl alcohol, 2% KOH, 28% dimethyl sulfoxide, and 11% 18-crown-6-ether,
based on the decontamination efficiency against mustard (HD). The
experimental results suggested that the volume ratio of the nonaqueous
decontaminant formula to CWA should be no less than 30, 2, and 10
for HD, soman (GD), and VX to achieve >99% in 30 min. The nonaqueous
decontaminant can be used to decontaminate CWAs over a wide range
of ambient temperature, especially low temperature. It was shown that
the main degradation pathway of HD was hydrochloric acid (HCl) elimination
to give chloroethyl vinyl sulfide. GD and VX degradation pathway involved
P–F and P–S bond cleavage, leading to nucleophilic displacement
reactions. The nonaqueous formula presented excellent performance
toward decontaminate CWAs contaminated concrete, alkyd paint coatings,
and military exposure suits. Corrosion of the formula to metal materials
and alkyd paint coatings was much lower than that by DS-2 decontamination
solution
Photosensitizer-Encapsulated Ferritins Mediate Photodynamic Therapy against Cancer-Associated Fibroblasts and Improve Tumor Accumulation of Nanoparticles
Nanoparticles
have been widely tested as drug delivery carriers
or imaging agents, largely because of their ability to selectively
accumulate in tumors through the enhanced permeability and retention
(EPR) effect. However, studies show that many tumors afford a less
efficient EPR effect and that many nanoparticles are trapped in the
perivascular region after extravasation and barely migrate into tumor
centers. This is to a large degree attributed to the dense tumor extracellular
matrix (ECM), which functions as a physical barrier to prevent efficient
nanoparticle extravasation and diffusion. In this study, we report
a photodynamic therapy (PDT) approach to enhance tumor uptake of nanoparticles.
Briefly, we encapsulate ZnF<sub>16</sub>Pc, a photosensitizer, into
ferritin nanocages, and then conjugate to the surface of the ferritin
a single chain viable fragment (scFv) sequence specific to fibroblast
activation protein (FAP). FAP is a plasma surface protein widely upregulated
in cancer-associated fibroblasts (CAFs), which is a major source of
the ECM fiber components. We found that the scFv-conjugated and ZnF<sub>16</sub>Pc-loaded ferritin nanoparticles (scFv-Z@FRT) can mediate
efficient and selective PDT, leading to eradication of CAFs in tumors.
When tested in bilateral 4T1 tumor models, we found that the tumor
accumulation of serum albumin (BSA), 10 nm quantum dots (QDs), and
50 nm QDs was increased by 2-, 3.5-, and 18-fold after scFv-Z@FRT
mediated PDT. Our studies suggest a novel and safe method to enhance
the delivery of nanoparticles to tumors
Evans Blue Derivative-Functionalized Gold Nanorods for Photothermal Therapy-Enhanced Tumor Chemotherapy
Chemotherapy
is a standard care for cancer management, but the lack of tumor targeting
and high dose-induced side effects still limit its utility in patients.
Here, we report a chemotherapy combined with photothermal therapy
(PTT) for enhanced cancer ablation by functionalization of gold nanorods
(GNRs) with a novel small molecule named truncated Evans blue (tEB).
On the basis of the high binding affinity of tEB with albumin, an
Abraxane-like nanodrug, human serum albumin/hydroxycamptothecin (HSA/HCPT),
was further complexed with GNR-tEB. This formed an HCPT/HSA/tEB-GNR
(HHEG) with excellent biostability and biocompatibility. With photoacoustic
and fluorescence imaging, we observed HHEG tumor targeting, which
is mediated by enhanced permeability retention effect. The accumulation
of HHEG peaked in tumor at 12 h postinjection. Moreover, HHEG can
effectively ablate tumor growth with laser illumination via chemo/thermal
therapy after intravenous administration into SCC7 tumor. This combination
is much better than chemotherapy or PTT alone. Collectively, we constructed
a chemo/thermal therapy nanostructure based on a tEB-modified GNR
for better tumor treatment effect. The use of tEB in gold nanoparticles
can facilitate many new approaches to design hybrid nanoparticles
The quantified analysis of <sup>99m</sup>Tc-RGD-BBN in major organs of healthy volunteers calculated from the whole-body images obtained at 10 min, 30 min, 1 h, 2 h, 4 h, 8 h and 24 h after administration.
<p>The quantified analysis of <sup>99m</sup>Tc-RGD-BBN in major organs of healthy volunteers calculated from the whole-body images obtained at 10 min, 30 min, 1 h, 2 h, 4 h, 8 h and 24 h after administration.</p
Scintimammography results versus final histopathological diagnosis of 36 patients.
<p>DCIS: ductal carcinoma in situ.</p><p>Scintimammography results versus final histopathological diagnosis of 36 patients.</p
Averaged time-activity curve of <sup>99m</sup>Tc-RGD-BBN in urine for all healthy volunteers.
<p>Error bars indicate standard deviations.</p
T/NT for <sup>99m</sup>Tc-RGD and <sup>99m</sup>Tc-MIBI in malignant and benign tumors.
<p>(A) The T/NT for <sup>99m</sup>Tc-RGD in breast cancer was significantly higher than that in benign lesions (p<0.001). (B) The T/NT for <sup>99m</sup>Tc-MIBI in breast cancer was significantly higher than that in benign lesions (p<0.001).</p