Polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X nanotheranostic platform for nasopharyngeal carcinoma imaging and photothermal therapy.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a type of head and neck malignant tumor with a high incidence in specific regional distribution, and its traditional therapies face some challenges. It has become an urgent need to seek new therapeutic strategies without or with low toxicity and side effects. At present, more and more researchers has been attracting attention by nanotheranostic platform. Therefore, our team synthesized the polyethylene glycol-coated ultrasmall superparamagnetic iron oxide nanoparticles-coupled sialyl Lewis X (USPIO-PEG-sLex) nanotheranostic platform with high temperature pyrolysis. RESULTS: The USPIO-PEG-sLex nanoparticles had excellent photothermal conversion property, and the temperature of USPIO-PEG-sLex nanoparticles solution increased with its concentration and power density of near-infrared (NIR) on 808 nm wavelengths. Five USPIO-PEG-sLex nanoparticles with different concentrations of 0 mg/ml, 0.025 mg/ml, 0.05 mg/ml, 0.1 mg/ml and 0.2 mg/ml were prepared. The biological toxicity results showed that the viability of NPC 5-8F cells is related to the concentration of USPIO-PEG-sLex nanoparticles and the culture time (P < 0.001). The results of photothermal therapy (PTT) in vitro indicated that the viability of 5-8F cells decreased significantly with the concentration of USPIO-PEG-sLex nanoparticles increases (P < 0.001), and the viability of NPC 5-8F cells were 91.04% ± 5.20%, 77.83% ± 3.01%, 73.48% ± 5.55%, 59.50% ± 10.98%, 17.11% ± 3.14%, respectively. The USPIO-PEG-sLex nanoparticles could target the tumor area, and reduce the T2* value of tumor tissue. The T2* values of tumor pre- and post-injection were 30.870 ± 5.604 and 18.335 ± 4.351, respectively (P < 0.001). In addition, USPIO-PEG-sLex nanoparticles as a photothermal agent for PTT could effectively inhibit tumor progression. The ratio of volume change between tail vein injection group, control group, nanoparticles without laser irradiation group and blank group after 5 treatments were 3.04 ± 0.57, 5.80 ± 1.06, 8.09 ± 1.96, 7.89 ± 2.20, respectively (P < 0.001). CONCLUSIONS: Our synthesized USPIO-PEG-sLex nanotheranostic platform, and it may be become a new strategy for the treatment of NPC.

Melanocortin 1 Receptor Targeted Imaging of Melanoma With Gold Nanocages and Positron Emission Tomography.

PURPOSE: Melanoma is a lethal skin cancer with unmet clinical needs for targeted imaging and therapy. Nanoscale materials conjugated with targeting components have shown great potential to improve tumor delivery efficiency while minimizing undesirable side effects in vivo. Herein, we proposed to develop targeted nanoparticles for melanoma theranostics. METHOD: In this work, gold nanocages (AuNCs) were conjugated with α-melanocyte-stimulating hormone (α-MSH) peptide and radiolabeled with 64Cu for melanocortin 1 receptor-(MC1R) targeted positron emission tomography (PET) in a mouse B16/F10 melanoma model. RESULTS: Their controlled synthesis and surface chemistry enabled well-defined structure and radiolabeling efficiency. In vivo pharmacokinetic evaluation demonstrated comparable organ distribution between the targeted and nontargeted AuNCs. However, micro-PET/computed tomography (CT) imaging demonstrated specific and improved tumor accumulation via MC1R-mediated delivery. By increasing the coverage density of α-MSH peptide on AuNCs, the tumor delivery efficiency was improved. CONCLUSION: The controlled synthesis, sensitive PET imaging, and optimal tumor targeting suggested the potential of targeted AuNCs for melanoma theranostics.

Influence of Polycaprolactone Concentration and Solvent Type on the Dimensions and Morphology of Electrosprayed Particles.

Polycaprolactone (PCL) micro- and nanoparticles produced using the electrospraying technique present high drug encapsulation capacity, a controllable surface area, and a good cost-benefit ratio. PCL is also considered a non-toxic polymeric material with excellent biocompatibility and biodegradability. All these characteristics make PCL micro- and nanoparticles a promising material for tissue engineering regeneration, drug delivery, and surface modification in dentistry. In this study, PCL electrosprayed specimens were produced and analyzed to determine their morphology and size. Three PCL concentrations (2, 4, and 6 wt%) and three solvent types (chloroform (CF), dimethylformamide (DMF), and acetic acid (AA)) with various solvent mixtures ratios (1:1 CF/DMF, 3:1 CF/DMF, 100% CF, 1:1 AA/CF, 3:1 AA/CF, and 100% AA) were used while keeping the remaining electrospray parameters constant. SEM images followed by ImageJ analysis showed a change in the morphology and size of the particles among various tested groups. A two-way ANOVA demonstrated a statistically significant interaction (p < 0.001) between PCL concentration and solvents on the size of the particles. With the increase in the PCL concentration, an increase in the number of fibers was observed among all the groups. The morphology and dimensions of the electrosprayed particles, as well as the presence of fibers, were significantly dependent on the PCL concentration, choice of solvent, and solvent ratio.

A 5-year follow-up study on the efficacy and safety of ultrasound-guided laser ablation in elderly patients with papillary thyroid microcarcinoma: A retrospective, single-center study from China.

Objective: The aim of this study is to evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of elderly patients with papillary thyroid microcarcinoma (PTMC). Methods: From September 2015 to April 2017, 38 elderly patients with PTMC confirmed through fine-needle aspiration biopsy (FNAB) were treated with PLA. Before the treatment, the location and volume of the nodule together with the patients' symptoms were evaluated. Twenty-four hours after the treatment, contrast-enhanced ultrasound (CEUS) was performed to evaluate the completeness of the ablation. To evaluate the volume of the ablation area and recurrence or metastasis, ultrasound examination was performed at 1, 3, 6, and 12 months after the treatment and every 6 months thereafter. FNAB was performed for any suspicious recurrence or metastasis lesions. Result: The ablation of all the 38 patients was all achieved completely as confirmed by CEUS. No obvious complications were found. The success rate of single ablation was 100%. The average follow-up time was 64.58 ± 5.29 months (60-78 months). By the time of the last follow-up, 31 (81.58%) ablation lesions disappeared completely and seven (18.42%) ablation lesions showed scar-like changes. The volume of nodules was 40.69 ± 16.45 mm3 before operation, which decreased to 0.22 ± 0.76 mm3 by the end of 42 months, and all nodules disappeared 4 years after ablation (P < 0.01). At 6, 12, 18, 24, 30, 36, and 42 months after ablation, the average volume reduction rates (VRRs) were 12.09%, 31.21%, 50.9%, 72.06%, 84.79%, 95.65%, and 100%, respectively. Of all the patients enrolled, one patient (2.6%) had local recurrence and was treated with PLA again. No regrowth of treated nodule or lymph node metastasis and distant metastases was detected. Conclusion: Ultrasound-guided PLA is effective and safe for the treatment of elderly patients with PTMC who are ineligible for surgery.

The value of ultrasound guided laser ablation in papillary thyroid recurrence carcinoma: A retrospective, single center study from China.

Objective: The efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for treating recurrent papillary thyroid cancer nodules (RPTCNs). Methods: A retrospective study was conducted in 43 patients with single recurrent thyroid cancer which was diagnosed by fine needle aspiration biopsy (FNAB). The extent of ablation was assessed by contrast-enhanced ultrasound (CEUS) 24h after PLA. At baseline (before ablation), 6, and 12 months, and every 6 months thereafter, the following were recorded: nodule maximum diameter, volume reduction rate (VRR), complications, and side effects. Result: All 43 patients were successfully treated with PLA without serious complications. All patients underwent CEUS 24 hours after PLA treatment, and all achieved complete ablation. The success rate of single ablation was 100%. The average follow-up time was 23.47 ± 6.50 months, 12 ~ 36 months. At the last follow-up, 32 (74.4%) ablation lesions disappeared completely and 11 (25.6%) ablation lesions showed scar-like changes. No lymph node metastasis was found during follow-up. The maximum diameter and volume of nodules decreased from 5.1 ± 1.4 mm, 86.22 ± 20.46 mm3 before operation to 0.73 ± 1.1 mm, 1.02 ± 1.92 mm3 at the end of observation (P < 0.01). The average volume reduction rates (VRR) at 6, 12, 18, 24, 30 and 36 months after ablation were 11.92%, 60.64%, 82.26%, 90.96%, 93.7% and 97.79% respectively. No regrowth of treated nodule and distant metastases were detected. One patient (2.3%) had local recurrence and was treated with PLA again. Conclusion: Ultrasound-guided PLA appears to be effective and safe for treating unifocal RPTCNs in selected patients who are ineligible for surgery, which is suitable for clinical application and promotion.

Gold Nanoparticles Doped with (199) Au Atoms and Their Use for Targeted Cancer Imaging by SPECT.

Gold nanoparticles have been labeled with various radionuclides and extensively explored for single photon emission computed tomography (SPECT) in the context of cancer diagnosis. The stability of most radiolabels, however, still needs to be improved for accurate detection of cancer biomarkers and thereby monitoring of tumor progression and metastasis. Here, the first synthesis of Au nanoparticles doped with (199)Au atoms for targeted SPECT tumor imaging in a mouse triple negative breast cancer (TNBC) model is reported. By directly incorporating (199)Au atoms into the crystal lattice of each Au nanoparticle, the stability of the radiolabel can be ensured. The synthetic procedure also allows for a precise control over both the radiochemistry and particle size. When conjugated with D-Ala1-peptide T-amide, the Au nanoparticles doped with (199)Au atoms can serve as a C-C chemokine receptor 5 (CCR5)-targeted nanoprobe for the sensitive and specific detection of both TNBC and its metastasis in a mouse tumor model.

Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters.

Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of (64)Cu alloyed gold nanoclusters ((64)CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled (64)Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the (64)CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.

Radioactive 198Au-doped nanostructures with different shapes for in vivo analyses of their biodistribution, tumor uptake, and intratumoral distribution.

With Au nanocages as an example, we recently demonstrated that radioactive (198)Au could be incorporated into the crystal lattice of Au nanostructures for simple and reliable quantification of their in vivo biodistribution by measuring the γ radiation from (198)Au decay and for optical imaging by detecting the Cerenkov radiation. Here we extend the capability of this strategy to synthesize radioactive (198)Au nanostructures with a similar size but different shapes and then compare their biodistribution, tumor uptake, and intratumoral distribution using a murine EMT6 breast cancer model. Specifically, we investigated Au nanospheres, nanodisks, nanorods, and cubic nanocages. After PEGylation, an aqueous suspension of the radioactive Au nanostructures was injected into a tumor-bearing mouse intravenously, and their biodistribution was measured from the γ radiation while their tumor uptake was directly imaged using the Cerenkov radiation. Significantly higher tumor uptake was observed for the Au nanospheres and nanodisks relative to the Au nanorods and nanocages at 24 h postinjection. Furthermore, autoradiographic imaging was performed on thin slices of the tumor after excision to resolve the intratumoral distributions of the nanostructures. While both the Au nanospheres and nanodisks were only observed on the surfaces of the tumors, the Au nanorods and nanocages were distributed throughout the tumors.

Chemoselective fabrication of high density peptide microarray by hetero-bifunctional tetra(ethylene glycol) linker for click chemistry conjugation.

A hetero-bifunctional tetra(ethylene glycol) molecule with silane and azide termini was synthesized, and this molecule was used to prepare azide-derivatized glass surface in one step. The resulting glass surface was available for fabricating peptide microarray by the conjugation with alkyne-containing peptide using click chemistry, which proceeded to the completion at low temperature and in aqueous solution. A high density of peptide on the surface was achieved due to concise overall procedure and highly efficient conjugation reaction. Immobilized peptides were highly bio-functional on the surface, as demonstrated by the ability to detect protease activity. Due to the biologically orthogonal manner of conjugation, peptide conjugated by site-specific immobilization was more accessible by protease than that conjugated by random amide conjugation. This site-specific and high efficient immobilization technique could be expanded to large scale development of biocompatible peptide and protein arrays for use in various applications.