Treatment Of Deep-seated Tumors Research Articles

Electrochemotherapy in Advanced Pancreatic Adenocarcinoma

Background: Electrochemotherapy is effective in treatment of various cutaneous tumors and could be translated into treatment of deep seated tumors. With this aim, a prospective clinical phase I/II study was conducted to evaluate feasibility, safety and efficacy of intraoperative Electrochemotherapy (ECT) in locally advanced pancreatic adenocarcinoma. Secondary endpoint was to evaluate treatment response in terms of quantitative morphological and functional criteria based on Magnetic Resonance Imaging.

Cis-Silicon phthalocyanine conformation endows J-aggregated nanosphere with unique near-infrared absorbance and fluorescence enhancement: a tumor sensitive phototheranostic agent with deep tissue penetrating ability.

Organic phototheranostic nanomedicines with an optimized near-infrared (NIR) biological transparent window (700-900 nm) are highly desirable for the diagnosis and treatment of deep-seated tumors in clinic. As excellent organic photosensitizers for photodynamic therapy (PDT) with outstanding photo- and thermo-stability, phthalocyanines (Pcs) have been used as the building blocks of single-component nanomedicines. However, to the best of our knowledge, all the Pc-based single-component self-assemblies reported to date are of an H-aggregate nature. This results in the simultaneous self-quenching of fluorescence emission and photodynamic activity as well as greatly reduced tissue penetration due to blue-shifted absorption. In the present work, intramolecular hydrogen bonding was formed between the two long and flexible axial NH2-terminated diethylene glycol ligands of the amphiphilic SiPc molecule (SiPc-NH2) in solution, leading to the employment of a cis-conformation of this molecule according to the 1H-NMR spectroscopy result, which as a building block then further self-assembled into monodisperse nanospheres (SiPcNano) with a J-aggregation nature on the basis of electronic absorption spectroscopic results. As a result, SiPcNano exhibited significantly enhanced red-shifted absorption in the NIR range of 750-850 nm and fluorescence emission. This in combination with the increased photodynamic effect for SiPcNano triggered by the protonation of amine groups due to the acidic nature of tumors endowed effective synergistic NIR photodynamic and photothermal effects in different cancer cells and thus effective inhibition of tumor growth in A549 tumor-bearing mice on the basis of a series of in vitro and in vivo evaluations. The present result provides a new approach for constructing novel single-component NIR organic nanomedicines for multifunctional cancer therapy.

Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications.

Photodynamic therapy (PDT) has shown great effectiveness in oncotherapy but has not been implemented in broad clinical applications because the limited penetration depth of the light used has been unable to reach deep-seated tumors. However, X-rays have been widely used in the clinical field for imaging and radiation therapy due to their excellent tissue penetration depth. Recently, X-rays have been established as an ideal excitation source for PDT, which holds great promise for breaking the depth limitation of traditional PDT for treatment of deep-seated tumors. This review aims to provide an overview of nanoscintillator-mediated X-ray induced PDT (X-PDT) including the concept, the design considerations of nanosensitizers for X-PDT, the modelling of nanosensitizer energy deposition, the putative mechanism by which X-PDT kills cells, and the prospects of future directions. We attempt to summarize the main developments that have occurred over the past decades. Possibilities and challenges for the clinical translation of X-PDT are also discussed.

Long-Circulating Prostate-Specific Membrane Antigen-Targeted NIR Phototheranostic Agent.

Targeted photodynamic therapy (PDT) combined with image-guided surgical resection is a promising strategy for precision cancer treatment. Prostate-specific membrane antigen (PSMA) is an attractive target due to its pronounced overexpression in a variety of tumors, most notably in prostate cancer. Recently, we reported a pyropheophorbide-based PSMA-targeted agent, which exhibited long plasma circulation time and effective tumor accumulation. To further advance PSMA-targeted photodynamic therapy by harvesting tissue-penetrating properties of the NIR light, we developed a bacteriochlorophyll-based PSMA-targeted photosensitizer (BPP), consisting of three building blocks: (1) a PSMA-affinity ligand, (2) a peptide linker to prolong plasma circulation time and (3) a bacteriochlorophyll photosensitizer for NIR fluorescence imaging and photodynamic therapy (Qy absorption maximum at 750nm). BPP exhibited excellent PSMA-targeting selectivity in both subcutaneous and orthotopic mouse models. The nine D-peptide linker in BPP structure prolonged its plasma circulation time (12.65h). Favorable pharmacokinetic properties combined with excellent targeting selectivity enabled effective BPP tumor accumulation, which led to effective PDT in a subcutaneous prostate adenocarcinoma mouse model. Overall, bright NIR fluorescence of BPP enables effective image guidance for surgical resection, while the combination of its targeting capabilities and PDT activity allows for potent and precise image-guided photodynamic treatment of PSMA-expressing tumors.

Recent Advances in Electrochemotherapy.

Electrochemotherapy is gaining recognition as an effective local therapy that uses systemically or intratumorally injected bleomycin or cisplatin with electroporation as a delivery system that brings drugs into the cells to exert their cytotoxic effects. Preclinical work is still ongoing, testing new drugs, seeking the best treatment combination with other treatment modalities, and exploring new sets of pulses for effective tissue electroporation. The applications of electrochemotherapy are being fully exploited in veterinary oncology, where electrochemotherapy, because of its simple execution, has a relatively good cost-benefit ratio and is used in the treatment of cutaneous tumors. In human oncology, electrochemotherapy is fully recognized as a local therapy for cutaneous tumors and metastases. Its effectiveness is being explored in combination with immunomodulatory drugs. However, the development of electrochemotherapy is directed into the treatment of deep-seated tumors with a percutaneous approach. Because of the vast number of reports, this review discusses the articles published in the past 5 years.

The role and mechanisms of zinc oxide nanoparticles in the improvement of the radiosensitivity of lung cancer cells in clinically relevant megavoltage radiation energies in-vitro

Objective(s): Semiconductor zinc oxide nanoparticles (ZnO NPs) have unique properties, such as inherent selectivity and photosensitization effects under ultraviolet (UV) radiation. ZnO NPs serve as promising anticancer agents. However, UV radiation limits their penetration into the body. In most clinical settings, it is essential to use high-energy photons in the treatment of deep-seated tumors. The present study aimed to evaluate the radiosensitization effects of ZnO NPs on human lung cancer cells under megavoltage (MV) X-ray irradiation. Materials and Methods: ZnO NPs with the mean diameter of seven nanometers were synthesized and characterized. The cytotoxicity and cellular uptake of ZnO NPs were evaluated in SKLC-6 lung cancer and MRC-5 normal lung cells using the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2H-tetrazolium (MTT) and inductively coupled plasma-mass spectrometry assays, respectively. In addition, the radiosensitization effects of ZnO NPs were investigated under MV irradiation using a clonogenic survival assay. Apoptosis induction and DNA damage were also evaluated using flow cytometry and cytokinesis-block micronucleus assay, respectively.Results: ZnO NPs were taken up and reduced the viability of the cancer cells at a higher rate compared to the normal cells. Moreover, ZnO NPs significantly enhanced the radiosensitivity of the cancer cells with the sensitizer enhancement ratios of 1.23 and 1.31 at the concentrations of 10 and 20 μg/ml, respectively. However, they had no significant effect on the radiosensitivity of the normal cells. Apoptosis induction and DNA damage also improved at a higher rate in the cancer cells compared to the normal cells with the combination of ZnO NPs with MV radiation.Conclusion: According to the results, ZnO NPs had the potential to be a selective radiosensitizer for lung cancer radiotherapy under MV X-ray irradiation. Some of the cytotoxic and genotoxic mechanisms in radiosensitization by ZnO NPs were elevated apoptosis induction and DNA damage levels.

Analysis of Photo Neutron Production From the Patient During Radiotherapy Treatment using CR 39 SSNTD

Most radiation treatments for curing cancer are completely non invasive. Usually patients will undergo radiation treatment to relieve symptoms and pain. The research focuses the various processes involved in generating photo neutron spectrum and dose proceeding from accelerator for treatment. The electrons are stimulated to high energies through a linear tube. These high-energy electron beams similarly treats shallow malignant growths. It tends to strike an objective to create x-ray beams for deep-seated tumor treatments. Hydrogen thyratrons are the direct current power supply for the modulator that has a pulse-forming network with switch tube. This results in a flat-topped high voltage pulse from the modulator area to DC pulse for a few microseconds of the period.Photo neutron spectrum and dose calculated. 15 MV lead to photo neutron production from many of the elements including Tungsten, Lead, Tantalum Nitrogen, Phosphorus and so on. Particularly 207Pb has photo neutron threshold as low as 6.74 MeV and 182W has threshold 8.04 MeV. Moreover, Nitrogen and Phosphorus have a lesser threshold for photo-proton emission at 7.55 MeV and 7.3 MeV respectively. Considering the radiation-weighting factor for neutrons, it is obvious that, the neutron dose considered in the treatment planning process, and we have to incorporate some mechanism in the radiotherapy treatment delivery for neutron free photons.

Codoping Enhanced Radioluminescence of Nanoscintillators for X-ray-Activated Synergistic Cancer Therapy and Prognosis Using Metabolomics.

Radio- and photodynamic therapies are the first line of cancer treatments but suffer from poor light penetration and less radiation accumulation in soft tissues with high radiation toxicity. Therefore, a multifunctional nanoplatform with diagnosis-assisted synergistic radio- and photodynamic therapy and tools facilitating early prognosis are urgently needed to fight the war against cancer. Further, integrating cancer therapy with untargeted metabolomic analysis would collectively offer clinical pertinence through facilitating early diagnosis and prognosis. Here, we enriched scintillation of CeF3 nanoparticles (NPs) through codoping Tb3+ and Gd3+ (CeF3:Gd3+,Tb3+) for viable clinical approach in the treatment of deep-seated tumors. The codoped CeF3:Gd3+,Tb3+ scintillating theranostic NPs were then coated with mesoporous silica, followed by loading with rose bengal (CGTS-RB) for later computed tomography (CT)- and magnetic resonance image (MRI)-guided X-ray stimulated synergistic radio- and photodynamic therapy (RT+XPDT) using low-dose, one-time X-ray irradiation. The results corroborated an efficient tumor regression with synergistic RT+XPDT relative to single RT. Global untargeted metabolome shifts highlighted the mechanism behind this efficient tumor regression using RT, and synergistic RT+XPDT treatment is due to the starvation of nonessential amino acids involved in protein and DNA synthesis and energy regulation pathways necessary for growth and progression. Our study also concluded that tumor and serum metabolites shift during disease progression and regression and serve as robust biomarkers for early assessment of disease state and prognosis. From our results, we propose that codoping is an effective and extendable technique to other materials for gaining high optical yield and multifunctionality and for use in diagnostic and therapeutic applications. Critically, the integration of multifunctional theranostic nanomedicines with metabolomics has excellent potential for the discovery of early metabolic biomarkers to aid in better clinical disease diagnosis and prognosis.

Low-Dose X-ray Excited Photodynamic Therapy Based on NaLuF4:Tb3+-Rose Bengal Nanocomposite.

X-ray excited photodynamic therapy (X-PDT), which utilizes X-rays as the energy source and X-ray luminescent nanoparticles (XLNPs) as the transducer to excite photosensitizers (PS), resolves the penetration problem of light in traditional PDT to enable the treatment of deep-seated tumors. Nevertheless, the high X-ray dosage used in X-PDT hampers its potential applications in clinics. In this study, to alleviate the dose problem, β-NaLuF4:Tb3+ spherical nanoparticles (NPs) with ultrastrong green X-ray excited optical luminescence (XEOL) due to the less nonradiative relaxation probability and high X-ray absorption mass coefficient, which perfectly matches the absorption spectrum of a photosensitizer named rose bengal (RB), were synthesized and employed as the energy transducer for X-PDT. After covalent conjugation of NPs with RB, high Förster resonant energy transfer (FRET) efficiency up to 94.29% was achieved, leading to high production of singlet oxygen. In vivo X-PDT efficacy was evaluated by nude mice with a HepG2 tumor xenograft. With excellent biocompatibility, the synthesized NPs-RB nanocomposite showed significant antitumor efficiency up to 80 ± 12.3% with a total X-ray dose of only 0.19 Gy, demonstrating the feasibility of low-dose X-PDT in vivo for the first time. The present work provides a promising platform for X-PDT in deep-seated tumors.

Carbon-Doped TiO2 Activated by X-Ray Irradiation for the Generation of Reactive Oxygen Species to Enhance Photodynamic Therapy in Tumor Treatment.

Traditional photodynamic therapy (PDT) is limited by the penetration depth of visible light. Although the light source has been changed to near infrared, infrared light is unable to overcome the penetration barrier and it is only effective at the surface of the tumors. In this study, we used X-ray as a light source for deep-seated tumor treatment. A particle with a narrow band gap when exposed to soft X-rays would produce reactive oxygen species (ROS) to kill tumor cell, with less damage to the normal tissues. Anatase TiO2 has been studied as a photosensitizer in PDT. In the experiment, C was doped into the anatase lattice at an optimum atomic ratio to make the band gap narrower, which would be activated by X-ray to produce more ROS and kill tumor cells under stress. The results showed that the synthesized TiO2:C particles were identified as crystal structures of anatase. The synthesized particles could be activated effectively by soft X-rays to produce ROS, to degrade methylene blue by up to 30.4%. Once TiO2:C was activated by X-ray irradiation, the death rate of A549 cells in in vitro testing was as high as 16.57%, on day 2. In the animal study, the tumor size gradually decreased after treatment with TiO2:C and exposure to X-rays on day 0 and day 8. On day 14, the tumor declined to nearly half of its initial volume, while the tumor in the control group was twice its initial volume. After the animal was sacrificed, blood, and major organs were harvested for further analysis and examination, with data fully supporting the safety of the treatment. Based on the results of the study, we believe that TiO2:C when exposed to X-rays could overcome the limitation of penetration depth and could improve PDT effects by inhibiting tumor growth effectively and safely, in vivo.

Electrochemotherapy in advanced pancreatic adenocarcinoma

Background: Electrochemotherapy(ECT) is effective in treatment of various cutaneous tumors and could be translated into treatment of deep seated tumors. A prospective phase I/II study was conducted to evaluate feasibility, safety and efficacy of intraoperative ECT for locally advanced pancreatic adenocarcinoma. Secondary endpoint was to evaluate treatment response in terms of quantitative morphological and functional criteria based on Magnetic Resonance Imaging(MRI). Methods: 12 consecutive patients were enrolled. ECT with bleomycin was performed during open surgery, by insertion of electrodes into and around the tumor according to the individualized treatment plan. All patients underwent MRI and CT scan, before and after ECT treatment, using morphological and functional imaging. RECIST criteria were used to evaluate ECT response on CT and quantitative parameters were used to evaluate ECT response on MRI. Results: No acute and/or postoperative serious adverse events related to ECT were observed; no clinically significant electrocardiographic, hemodynamic, or serum biologic changes were noted. No clinically relevant elevation of amylase or lipase levels was observed in any patient and no bleeding or damage to surrounding viscera occured. Functional imaging based on MRI has shown more suitable to evaluate ECT response than CT. Conclusion: ECT of locally advanced pancreatic adenocarcinoma proved to be feasible, safe and effective. Dynamic and diffusion MRI seemed to be more suitable to assess ECT response than CT imaging.

Development of a novel anti-tumor theranostic platform: a near-infrared molecular upconversion sensitizer for deep-seated cancer photodynamic therapy.

Upconversion-based photon-initiated therapeutic modalities, photodynamic therapy (PDT) in particular, have shown significant clinical potential in deep-seated tumor treatment. However, traditional multiphoton upconversion materials involving lanthanide (ion)-doped upconversion nanoparticles (UCNPs) and two-photon absorption (TPA) dyes often suffer from lots of inherent problems such as unknown systematic toxicity, low reproducibility, and extremely high irradiation intensity for realization of multiphoton upconversion excitation. Herein, for the first time, we report a one-photon excitation molecular photosensitizer (FUCP-1) based on a frequency upconversion luminescence (FUCL) mechanism. Under anti-Stokes (808 nm) excitation, FUCP-1 showed excellent photostability and outstanding upconversion luminescence quantum yield (up to 12.6%) for imaging-guided PDT. In vitro cellular toxicity evaluation presented outstanding inhibition of 4T1 cells by FUCP-1 with 808 nm laser irradiation (the half maximal inhibitory concentration was as low as 2.06 μM). After intravenous injection, FUCP-1 could specifically accumulate at tumor sites and obviously suppress the growth of deep-seated tumors during PDT. More importantly, FUCP-1 could be fully metabolized from the body within 24 h, thus dramatically minimizing systemic toxicity. This study might pave a new way for upconversion-based deep-seated cancer PDT.

Near-infrared light-regulated cancer theranostic nanoplatform based on aggregation-induced emission luminogen encapsulated upconversion nanoparticles.

Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors.Methods: We present a facile strategy for constructing a NIR-regulated cancer theranostic nanoplatform by encapsulating upconversion nanoparticles (UCNPs) and a luminogen (2-(2,6-bis((E)-4-(phenyl(40-(1,2,2-triphenylvinyl)-[1,10-biphenyl]-4-yl)amino)styryl)-4H-pyran-4-ylidene)malononitrile, TTD) with aggregation-induced emission (AIEgen) characteristics using an amphiphilic polymer, and further conjugating cyclic arginine-glycine-aspartic acid (cRGD) peptide to yield UCNP@TTD-cRGD NPs. We then evaluated the bioimaging and anti-tumor capability of the UCNP@TTD-cRGD NPs under NIR light illumination in an in vitro three-dimensional (3D) cancer spheroid and in a murine tumor model, respectively.Results: With a close match between the UCNP emission and absorption of the AIEgen, the synthesized NPs could efficiently generate ROS, even under excitation through thick tissues. The NIR-regulated UCNP@TTD-cRGD NPs that were developed could selectively light up the targeted cancer cells and significantly inhibit tumor growth during the NIR-regulated PDT treatment as compared with the cells under white light excitation.Conclusion: In summary, the synthesized UCNP@TTD-cRGD NPs showed great potential in NIR light-regulated photodynamic therapy of deep-seated tumors. Our study will inspire further exploration of novel theranostic nanoplatforms that combine UCNPs and various AIEgen PSs for the advancement of deep-seated tumor treatments with potential clinical translations.

Beam shaping assembly design of 7Li(p,n)7Be neutron source for boron neutron capture therapy of deep-seated tumor

The development of a medical facility for boron neutron capture therapy at Budker Institute of Nuclear Physics is under way. The neutron source is based on a tandem accelerator with vacuum insulation and lithium target. The proposed accelerator is conceived to deliver a proton beam around 10 mA at 2.3 MeV proton beam.To deliver a therapeutic beam for treatment of deep-seated tumors a typical Beam Shaping Assembly (BSA) based on the source specifications has been explored. In this article, an optimized BSA based on the 7Li(p,n)7Be neutron production reaction is proposed.To evaluate the performance of the designed beam in a phantom, the parameters and the dose profiles in tissues due to the irradiation have been considered.In the simulations, we considered a proton energy of 2.3 MeV, a current of 10 mA, and boron concentrations in tumor, healthy tissues and skin of 52.5 ppm, 15 ppm and 22.5 ppm, respectively. It is found that, for a maximum punctual healthy tissue dose seated to 11 RBE-Gy, a mean dose of 56.5 RBE Gy with a minimum of 52.2 RBE Gy can be delivered to a tumor in 40 min, where the therapeutic ratio is estimated to 5.38.All of these calculations were carried out using the Monte Carlo MCNP code.

Acoustic and Thermal Field Modelling for Ablation Using High Intensity Focused Ultrasound (December 2017)

Focused Ultrasound Surgery is gaining impetus as a non-invasive ablation modality for treatment of deep seated tumors and cancers over the years. The main advantages lie in its ionization free nature over other prevalent modalities for ablation. However, due to the ability of irreversible damage, it is extremely important to understand the multi-physics of parametric influence in dose selection and planning as well as implementing precise and accurate targeting means for selective desirable damage. This paper deals with the field modelling of ultrasonic sources, lesion formation and subsequent thermal distribution studies during the lesioning process for liver cancer targets.

Biodegradable Polymer Nanoparticles for Photodynamic Therapy by Bioluminescence Resonance Energy Transfer.

Conventional photodynamic therapy is severely constrained by the limited light-penetration depth in tissue. Here, we show efficient photodynamic therapy (PDT) mediated by bioluminescence resonance energy transfer (BRET) that overcomes the light-penetration limitation. The photosensitizer Rose Bengal (RB) was loaded in biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which were then conjugated with firefly luciferase. Spectroscopic characterizations indicated that BRET effectively activated RB to generate reactive oxygen species (ROS). In vitro studies of the cellular cytotoxicity and photodynamic effect indicated that cancer cells were effectively destroyed by BRET-PDT treatment. In vivo studies in a tumor-bearing mouse model demonstrated that tumor growth was significantly inhibited by BRET-PDT in the absence of external light irradiation. The BRET-mediated phototherapy provides a promising approach to overcome the light-penetration limitation in photodynamic treatment of deep-seated tumors.

MICRODOSIMETRIC APPLICATIONS IN PROTON AND HEAVY ION THERAPY USING SILICON MICRODOSIMETERS.

Using the CMRP 'bridge' μ+ probe, microdosimetric measurements were undertaken out-of-field using a therapeutic scanning proton pencil beam and in-field using a 12C ion therapy field. These measurements were undertaken at Mayo Clinic, Rochester, USA and at HIMAC, Chiba, Japan, respectively. For a typical proton field used in the treatment of deep-seated tumors, we observed dose-equivalent values ranging from 0.62 to 0.99 mSv/Gy at locations downstream of the distal edge. Lateral measurements at depths close to the entrance and along the SOBP plateau were found to reach maximum values of 3.1 mSv/Gy and 5.3 mSv/Gy at 10 mm from the field edge, respectively, and decreased to ~0.04 mSv/Gy 120 mm from the field edge. The ability to measure the dose-equivalent with high spatial resolution is particularly relevant to healthy tissue dose calculations in hadron therapy treatments. We have also shown qualitatively and quantitively the effects critical organ motion would have in treatment using microdosimetric spectra. Large differences in spectra and RBE10 were observed for treatments where miscalculations of 12C ion range would result in critical structures being irradiated, showing the importance of motion management.

Measurements of 12C ions beam fragmentation at large angle with an Emulsion Cloud Chamber

Hadron radiotherapy is a powerful technique for the treatment of deep-seated tumours. The physical dose distribution of hadron beams is characterized by a small dose delivered in the entrance channel and a large dose in the Bragg peak area. Fragmentation of the incident particles and struck nuclei occurs along the hadron path. Knowledge of the fragment energies and angular distributions is crucial for the validation of the models used in treatment planning systems. We report on large angle fragmentation measurements of a 400 MeV/n 12C beam impinging on a composite target at the GSI laboratory in Germany. The detector was made of 300 micron thick nuclear emulsion films, with sub-micrometric spatial resolution and large angle track detection capability, interleaved with passive material. Thanks to newly developed techniques in the automated scanning of emulsions it was possible to extend the angular range of detected particles. This resulted in the first measurement of the angular and momentum spectrum for fragments emitted in the range from 34̂ to 81̂.

STUDY OF SUBCELLULAR DISTRIBUTION OF CRYSTALLINE MESO-TETRA(3-PYRIDYL)BACTERIOCHLORIN NANOPARTICLES

The results of the study of subcellular distribution of molecular meso-tetra(3-pyridyl)bacteriochlorin nanocrystals proposed as therapeutic agents for photodynamic therapy are represented in the article. Investigations and measurement of spectroscopic properties of molecular crystals of near-infrared photosensitizer were conducted using special device complex based on fiber-optic spectrometer. Investigation and analysis of the pattern of subcellular accumulation of meso-tetra(3-pyridyl)bacteriochlorin in molecular (dimethyl sulfoxide (DMSO) as solvent) and nanocrystalline forms on different cell lines: human monocytes (THP-1), human cervical cancer cells (HeLa) and mouse malignant brain tumor cells (glioma C6). The dynamics of subcellylar accumulation of the agent at concentration of 5 and 10 mg/l was assessed with laser microscope-spectrum analyzer and by confocal microscopy. The study showed that in the course of interaction with cell lines molecular nanocrystals of the agent developed ability to fluorescence. Hence, in the cellular environment meso-tetra(3-pyridyl) bacteriochlorin nanoparticles became phototoxic giving opportunities for their use for fluorescence diagnosis and photodynamic therapy. Specific role of meso-tetra(3-pyridyl)bacteriochlorin in the range of photosensitizers is determined by its spectral characteristics, i.e. absorption and fluorescence in near-infrared band, which allows measuring and affecting on deeper layers of biotissue. Thus, the use of meso-tetra(3-pyridyl)bacteriochlorin nanoparticles as nanophotosensitizers may improve the efficacy of diagnosis and treatment of deep-seated tumors.

Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles.

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.