Non-invasive Cancer Treatment Research Articles

In Vitro Thermal Assessment of Vascularized Tissue Phantom in Presence of Gold Nanorods During Photo-Thermal Therapy

Abstract Nowadays, laser and nanotechnology have drawn more attention in the field of noninvasive cancer treatment with precise ablation of tumor preserving the surrounding healthy tissue. Besides, the assessment of viscoelastic deformation within the tissue can estimate the thermally induced nociceptive pain during laser therapy. This study deals with a laser-assisted in vitro thermal analysis on vascular tissue phantom doped with gold nanorods along with a comparative study with numerical results. The prediction of tissue thermomechanical response under laser heating also has been made. Both Pennes and dual-phase-lag bioheat equations coupled with equilibrium equations are solved using comsolmultiphysics (Bangalore, India). The aim is to create a comparative study between intratumoral (IT) and intravenous (IV) infusion schemes of nanoparticles in terms of thermal and mechanical behavior. The in vitro heating of tissue phantom with IT scheme provides more control over the spreading of necrotic temperature in terms of precise damage of the targeted area, preserving the surrounding nontargeted area. Predicted results show a reduced overall thermal deformation of the nanoparticle doped tissue model with the IT scheme depicting a stiffer thermoelastic response comparing the model doped with the IV scheme. The simultaneous heating and cooling shows a viscoelastic nature of biotissue. However, under cyclic heating and cooling of the tissue model embedded in a large blood vessel (LBV) depicts a smaller sized stress–strain hysteresis loop. Nevertheless, the present findings can help to understand the thermo-mechanical behavior of tissue during clinical photothermal therapy.

A Physically Triggered Cell Death via Transbarrier Cold Atmospheric Plasma Cancer Treatment.

Cold atmospheric plasma (CAP) is a near room-temperature ionized gas composed of highly reactive species. CAP also generates thermal radiation, ultraviolet radiation, and electromagnetic (EM) waves. So far, nearly all biological effects of CAP have relied on the chemical factors in CAP. Here, we first show that the EM emission from CAP can lead to the death of melanoma cells via a transbarrier contactless method. Compared with reactive species, the effect of the physical factors causes much stronger growth inhibition on a reactive species-resistant melanoma cell line B16F10. Such a physically triggered growth inhibition is due to a new cell death type, characterized by the rapid leakage of bulk solutions from the cells, resulting in cytoplasm shrinkage and bubbling on the cell membrane. The physically based CAP-triggered cell death can occur even there is a macroscale gap between the bulk CAP and cells, which includes an air gap (∼8 mm) and a dielectric material of the dish or plate (∼1 mm). Either a too large or a too small gap will inhibit such cell death. The physically triggered cellular pressure may cause the bubbling on cells, which can be inhibited in a hypotonic environment via the extracellular osmotic pressure. This study builds a foundation to use CAP as a physically based noninvasive cancer treatment.

Mitoxantrone as photothermal agents for ultrasound/fluorescence imaging-guided chemo-phototherapy enhanced by intratumoral H2O2-Induced CO

Multimodal imaging integrated theranostic nanomaterials provides broad prospects for noninvasive and precise cancer treatment. However, the uncertain physiological metabolism of the existing phototherapy nanoagents greatly prevents its clinical application. Herein, a smart nanoplatform based on clinically chemotherapeutic drugs mitoxantrone (MTO) was prepared to realize ultrasound/fluorescence imaging-guided chemo-photothermal combined therapy. The nanoplatform encapsulating MTO and manganese carbonyl (MnCO), which denoted as MCMA NPs, could accumulate at tumor sites by enhanced permeability and retention (EPR) effect and effectively induce cell apoptosis. MTO with near-infrared absorption (~676 nm) not only acted as chemotherapy drug, but also served as photothermal reagent with high photothermal conversion efficiency (ƞ = 42.2%). Especially, H2O2 in tumor sites and the photothermal effect of MTO could trigger MnCO to generate CO, which made cancer cells more sensitive to MTO and significantly alleviated cell resistance. Simultaneously, CO released in tumor also could act as contrast agent for tumor ultrasound imaging to provide accurate guidance for anticancer treatment. Moreover, MCMA NPs could further promote oxidative stress damage in mitochondria and protect normal cells from side effects of chemotherapy. Both in vivo and in vitro studies indicated that MCMA NPs possessed excellent synergetic tumor inhibition ability with high efficiency and low chemotherapy resistance.

Experimental investigation of effect of ultrasonic duty cycle on generation of reactive oxygen species for highly efficient sonodynamic treatment

Sonodynamic treatment (SDT) is a non-invasive treatment of cancer, combining ultrasound, reactive oxygen species (ROS), and sonosensitizer. When cavitation bubbles generated by ultrasound oscillate and collapse, ROS are generated due to the high temperature and high pressure inside the bubble. By generating cavitation bubbles in a target tissue, it can be treated by the cytotoxicity of ROS, which can be further enhanced by a sonosensitizer. In SDT, the small treatment region by a single shot of HIFU results in a long treatment time, which needs to be reduced by improving the efficiency of ROS generation. ROS can be visualized by the sonochemiluminescence of luminol. In this study, a polyacrylamide gel soaked with luminol solution is used as a target of ultrasonic exposure. The effect of the duty cycle of HIFU exposure on ROS generation was investigated by capturing sonochemiluminescent light emission, and high-speed photography of cavitation bubbles.

Delivery of MutT homolog 1 inhibitor by functionalized graphene oxide nanoparticles for enhanced chemo-photodynamic therapy triggers cell death in osteosarcoma

Photodynamic therapy (PDT) generates highly toxic reactive oxygen species (ROS) during noninvasive cancer treatment. MutT homolog 1 (MTH1) protein is a DNA oxidative damage repair protease and suppressing its function may provide a strategy to enhance PDT efficacy by improving cellular sensitivity to ROS. A nanoparticle, composed of functional graphene oxide (GO) conjugated with polyethylene glycol (PEG), folic acid (FA) and photosensitizer indocyanine green (ICG), was constructed to deliver MTH1 inhibitor (TH287) and doxorubicin. The effects of this nanoparticle on biological properties and cell death of osteosarcoma cells were investigated. We further examined the endoplasmic reticulum (ER) stress and apoptosis in osteosarcoma. A xenograft tumor model was used to validate the results in vivo. This drug-carrying PEG-GO-FA/ICG nanoparticle showed combined chemo-photodynamic therapy (Chemo-PDT) to inhibit the proliferation and migration of osteosarcoma cells. Enhanced Chemo-PDT promoted both apoptosis and autophagy by suppressing the MTH1 protein and promoting the accumulation of ROS. In this study, autophagy served as a rescue pathway against cell death, and suppressing autophagy enhanced the anti-cancer effects of Chemo-PDT. However, Chemo-PDT induced apoptosis was related to the occurrence of ER stress. ROS might contribute to ER stress and further induce apoptosis via the JNK/p53/p21 pathway. These findings provide a mechanistic understanding of nanoparticle-induced cell death in osteosarcoma. The combination of Chemo-PDT with other therapies is promising as a new strategy to treat osteosarcoma. Statement of significanceAdministration of chemotherapeutic drugs by traditional methods still has many problems. We designed a functionalized graphene oxide drug delivery system to deliver the photosensitizer indocyanine green, doxorubicin, and MTH1 inhibitor TH287. This nano delivery system showed combined chemo-photodynamic effects to inhibit osteosarcoma. Suppressing MTH1 protein might induce “phenotypic lethality” and enhance chemo-photodynamic therapy efficacy by improving cellular sensitivity to reactive oxygen species.

Fe3O4 Mesocrystals with Distinctive Magnetothermal and Nanoenzyme Activity Enabling Self-Reinforcing Synergistic Cancer Therapy.

Magnetite (Fe3O4) nanoparticles have been extensively used in noninvasive cancer treatment, for example, magnetic hyperthermia (MH) and chemodynamic therapy (CDT). However, how to achieve a highly efficient MH-CDT synergistic therapy based only on a single component of Fe3O4 still remains a challenge. Herein, hollow Fe3O4 mesocrystals (MCs) are constructed via a modified solvothermal method. Owing to the distinctive magnetic property of the mesocrystalline structure, Fe3O4 MCs show excellent magnetothermal conversion efficiency with a specific absorption rate of 722 w g-1 at a Fe concentration of 0.6 mg mL-1, much higher than that of Fe3O4 polycrystals (PCs). Moreover, Fe3O4 MCs also exhibit higher peroxidase-like activity than Fe3O4 PCs, which may be ascribed to the higher ratio of Fe2+/Fe3+ and more oxygen defects in the Fe3O4 MCs. Detailed in vivo results confirm that Fe3O4 MCs can instantly initiate CDT by producing the detrimental •OH, and such boosted reactive oxygen levels not only induces cell apoptosis but also reduces the expression of heat shock proteins, thus enabling low-temperature-mediated MH. More importantly, the in situ rising temperature resulted from MH in turn facilitates CDT, thus achieving a self-augmented synergistic effect between MH and CDT.

CT derived radiomic score for predicting the added benefit of adjuvant chemotherapy following surgery in stage I, II resectable non-small cell lung cancer: a retrospective multicohort study for outcome prediction

Use of adjuvant chemotherapy in patients with early-stage lung cancer is controversial because no definite biomarker exists to identify patients who would receive added benefit from it. We aimed to develop and validate a quantitative radiomic risk score (QuRiS) and associated nomogram (QuRNom) for early-stage non-small cell lung cancer (NSCLC) that is prognostic of disease-free survival and predictive of the added benefit of adjuvant chemotherapy following surgery. We did a retrospective multicohort study of individuals with early-stage NSCLC (stage I and II) who either received surgery alone or surgery plus adjuvant chemotherapy. We selected patients for whom we had available pre-treatment diagnostic CT scans and corresponding survival information. We used radiomic texture features derived from within and outside the primary lung nodule on chest CT scans of patients from the Cleveland Clinic Foundation (Cleveland, OH, USA; cohort D1) to develop QuRiS. A least absolute shrinkage and selection operator-Cox regularisation model was used for data dimension reduction, feature selection, and QuRiS construction. QuRiS was independently validated on a cohort of patients from the University of Pennsylvania (Philadephia, PA, USA; cohort D2) and a cohort of patients whose CT scans were derived from The Cancer Imaging Archive (cohort D3). QuRNom was constructed by integrating QuRiS with tumour and node descriptors (according to the tumour, node, metastasis staging system) and lymphovascular invasion. The primary endpoint of the study was the assessment of the performance of QuRiS and QuRNom in predicting disease-free survival. The added benefit of adjuvant chemotherapy estimated using QuRiS and QuRNom was validated by comparing patients who received adjuvant chemotherapy versus patients who underwent surgery alone in cohorts D1-D3. We included: 329 patients in cohort D1 (73 [22%] had surgery plus adjuvant chemotherapy and 256 (78%) had surgery alone); 114 patients in cohort D2 (33 [29%] had surgery plus adjuvant chemotherapy and 81 (71%) had surgery alone); and 82 patients in cohort D3 (24 [29%] had surgery plus adjuvant chemotherapy and 58 (71%) had surgery alone). QuRiS comprised three intratumoral and 10 peritumoral CT-radiomic features and was found to be significantly associated with disease-free survival (ie, prognostic validation of QuRiS; hazard ratio for predicted high-risk vs predicted low-risk groups 1·56, 95% CI 1·08-2·23, p=0·016 for cohort D1; 2·66, 1·24-5·68, p=0·011 for cohort D2; and 2·67, 1·39-5·11, p=0·0029 for cohort D3). To validate the predictive performance of QuRiS, patients were partitioned into three risk groups (high, intermediate, and low risk) on the basis of their corresponding QuRiS. Patients in the high-risk group were observed to have significantly longer survival with adjuvant chemotherapy than patients who underwent surgery alone (0·27, 0·08-0·95, p=0·042, for cohort D1; 0·08, 0·01-0·42, p=0·0029, for cohorts D2 and D3 combined). As concerns QuRNom, the nomogram-estimated survival benefit was predictive of the actual efficacy of adjuvant chemotherapy (0·25, 0·12-0·55, p<0·0001, for cohort D1; 0·13, <0·01-0·99, p=0·0019 for cohort D3). QuRiS and QuRNom were validated as being prognostic of disease-free survival and predictive of the added benefit of adjuvant chemotherapy, especially in clinically defined low-risk groups. Since QuRiS is based on routine chest CT imaging, with additional multisite independent validation it could potentially be employed for decision management in non-invasive treatment of resectable lung cancer. National Cancer Institute of the US National Institutes of Health, National Center for Research Resources, US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, Department of Defence, National Institute of Diabetes and Digestive and Kidney Diseases, Wallace H Coulter Foundation, Case Western Reserve University, and Dana Foundation.

Applications of Micro/Nanotechnology in Ultrasound-based Drug Delivery and Therapy for Tumor.

Ultrasound has been broadly used in biomedicine for both tumor diagnosis as well as therapy. The applications of recent developments in micro/nanotechnology promote the development of ultrasound-based biomedicine, especially in the field of ultrasound-based drug delivery and tumor therapy. Ultrasound can activate nano-sized drug delivery systems by different mechanisms for ultrasound- triggered on-demand drug release targeted only at the tumor sites. Ultrasound Targeted Microbubble Destruction (UTMD) technology can not only increase the permeability of vasculature and cell membrane via sonoporation effect but also achieve in situ conversion of microbubbles into nanoparticles to promote cellular uptake and therapeutic efficacy. Furthermore, High Intensity Focused Ultrasound (HIFU), or Sonodynamic Therapy (SDT), is considered to be one of the most promising and representative non-invasive treatment for cancer. However, their application in the treatment process is still limited due to their critical treatment efficiency issues. Fortunately, recently developed micro/nanotechnology offer an opportunity to solve these problems, thus improving the therapeutic effect of cancer. This review summarizes and discusses the recent developments in the design of micro- and nano- materials for ultrasound-based biomedicine applications.

Noninvasive treatment of organ-confined prostate cancer in elderly patients-results of the HAROW study

Noninvasive treatment options such as active surveillance (AS), watchful waiting (WW), and hormone deprivation therapy (HT) are particularly important in elderly patients with localized prostate cancer (PCa). We examine the use of these noninvasive treatment options in the everyday care in acohort of patients ≥70years old. In the HAROW study, the treatment of localized PCa under everyday conditions is investigated. The only inclusion criterion was newly diagnosed organ-confined PCa (≤cT2c). In AS, WW, and HT patients, we compared initial tumor and patient characteristics, follow-up examinations and changes of therapy. Of 457 patients ≥70years, 210 chose AS, 160 HT, and 87WW. Observation times were 6.3 years (AS), 7.5 years (HT), and 7.0 years (WW). AS patients (73.2 years) were younger than WW (76.0 years) and HT patients (76.9 years) and had ahigher proportion of low-risk tumors (80%) versus WW (31%) and HT (19%). Achange of therapy was observed in 47.1% of AS, 17.2% of WW and 13.1% of HT patients. Metastasis occurred in 1.0% of AS, 4.6% of WW, and 6.9% of HT patients. Overall survival was 94.3% for AS, 90.8% for WW and 81.9% for HT. Within the first 28.4months, the mean number of PSA determinations did not differ between AS and WW (6.1 vs. 5.2; p = 0.09); arebiopsy was performed in 37.6% of AS, 11.4% of WW, and 17% of HT patients. The allocation to curative and palliative strategies should be made according to patient and tumor characteristics by definition. Palliative procedures may represent concepts in older patients who initially chose acurative AS strategy.

PMAO-assisted thermal decomposition synthesis of high-stability ferrofluid based on magnetite nanoparticles for hyperthermia and MRI applications

The combination of magnetic fluid hyperthermia and magnetic resonance imaging is recently considered to be one of the most promising non-invasive cancer treatment. In this work, a highly stable ferrofluid based on magnetite nanoparticles with high magnetization and high specific absorption rate will be developed. The ferrofluid was synthesized by thermal decomposition using poly (maleic anhydride-alt-1-octadecene, noted as PMAO) as a phase transferring ligand. The results have demonstrated that the magnetic particles were fully covered at high coverage by long non-magnetic polymeric chains. The particle size was increased by 25–30% while the saturation magnetization was decreased approximately 7–9% after phase transfer process. Remarkably, the prepared ferrofluid revealed excellent colloidal stability over six months of storage with zeta potentials less than −40 mV. As consequently, a relatively high specific absorption rate of 66 W.g-1 was obtained at ferrofluid concentration of only 5 mg.mL-1. Additionally, high-resolution magnetic resonance images with improved transverse relaxation T2 were observed when using magnetite-based ferrofluid for both in-vitro and in-vivo tests. This study demonstrates a novel approach for tailoring magnetic nanoparticles applicable in magnetic fluid hyperthermia and imaging of tumor cells.

Three dimensional mesoporous carbon nanospheres as carriers for chemo-photothermal therapy compared with two dimensional graphene oxide nanosheets

Recent years, photothermal therapy (PTT) as a noninvasive cancer treatment has attracted wide interests of researchers worldwide. Platforms which can transform near infrared (NIR) laser power into heat play vital roles in PTT. In this paper, mesoporous carbon nanospheres (MCN) and graphene oxide nanosheets (GO), two widely used platforms in cancer treatment were compared in photothermal effect induced by NIR as well as the drug loading and release behaviors of the model drug doxorubicin (DOX). MCN and GO were grafted with polyethylene glycol (PEG) to improve the biocompatibility and aqueous stability. The elevated temperature of MCN-PEG was obviously superior to GO-PEG both in vitro and cellular photothermal effect. MCN-PEG and GO-PEG showed photothermal stability under repeated NIR irradiation. Additionally, the photothermal conversion efficiency (η) of MCN-PEG was calculated to be 32.24 %, which was higher than that of GO-PEG (27.13 %). Both nanovehicles had the similar drug loading capacities, however, the accumulative release rate of DOX/MCN-PEG was 1.6 times higher than DOX/GO-PEG in the pH 5.0 phosphate buffer solutions (PBS) exposed to NIR laser. Moreover, the cell viability assays and cellular uptake experiments validated that DOX/MCN-PEG possessed more excellent synergetic effect in chemo-photothermal therapy with the combination index (CI) of 0.443 compared with DOX/GO-PEG (0.661).

Photothermally enhanced photodynamic therapy based on glutathione-responsive pheophorbide a-conjugated gold nanorod formulations for cancer theranostic applications

Nanocarriers have provided a new platform for the selective delivery of therapeutic agents into targeted cells and tissues using safe, efficient, and tractable routes. In particular, the integration of multiple therapeutic/diagnostic modalities into a single system has the great potential of enhancing theranostic efficiency against serious diseases with reduced side effects. In this study, a new light-triggered theranostic system using photosensitizer-conjugated gold nanorods (AuNR) with glutathione (GSH)-sensitive linkages was developed for cancer imaging and combinational phototherapy of photodynamic therapy (PDT) and photothermal therapy (PTT) to achieve a synergistic cancer treatment. AuNRs with various aspect ratios were prepared as photothermal agents, and then a folic acid (FA)-PEG block copolymer (FAP) and pheophorbide a (Pheo) were chemically conjugated to the surface of AuNRs for active tumor targeting and PDT, respectively. The configuration of Pheo-conjugated AuNR nanocarriers has been precisely controlled through adjusting the feed composition ratio and the relationship between aspect ratio and absorption band of AuNRs. In particular, an AuNR with an aspect ratio of 3.84 and longitudinal plasmon resonance at 873nm (Pheo-conjugated AuNR100) exhibited superior performance in singlet oxygen generation, photothermal conversion effect, and GSH-mediated selective release of Pheo. Moreover, it also showed tumor targeting activity and a PDT-PTT synergistic effect. These results indicate that this multifunctional AuNR system with tumor targeting ability and GSH-sensitive linkages would be highly efficient for noninvasive cancer treatment by integrating cancer imaging diagnostics and synergistic therapy.

Inhalable Lactoferrin/Chondroitin-Functionalized Monoolein Nanocomposites for Localized Lung Cancer Targeting.

Localized drug delivery to lung cancer can overcome the limitations of systemic nanocarriers including low drug amounts reaching lung tissues and severe off-target toxicity. The current work presented novel inhalable nanocomposites as noninvasive platforms for lung cancer therapy. Nanoparticulate liquid crystals (LCNPs) based on monoolein were developed for synergistic co-encapsulation of the cytotoxic chemotherapeutic drug, pemetrexed, and the phytoherbal drug, resveratrol (PEM-RES-LCNPs). For active tumor targeting, lactoferrin (LF) and chondroitin sulfate (CS), natural polymers with intrinsic tumor-targeting capabilities, were exploited to functionalize the surface of LCNPs using a layer-by-layer (LbL) self-assembly approach. To maximize their deep lung deposition, LF/CS-coated PEM-RES-LCNPs were then microencapsulated within various carriers to obtain inhalable nanocomposites via spray-drying techniques. The inhalable dry powder nanocomposites prepared using a mannitol-inulin-leucine (1:1:1 wt) mixture displayed superior in vitro aerosolization performance (2.72 μm of MMAD and 61.6% FPF), which ensured deep lung deposition. In lung cancer-bearing mice using urethane as a chemical carcinogen, the inhalable LF/CS-coated PEM-RES-LCNP nanocomposites showed superior antitumor activity as revealed by a considerable decrease of the average lung weight, reduced number and diameter of cancerous lung foci, decreased expression of VEGF-1, and increased expression of active caspase-3 as well as reduced Ki-67 expression compared to the spray-dried free PEM/RES powder mixture and positive control. Moreover, the in vivo fluorescence imaging confirmed successful lung deposition of the inhalable nanocomposites. Conclusively, the inhalable liquid crystalline nanocomposites elaborated in the current work could open new avenues for noninvasive lung cancer treatment.

Enzyme-Assisted Photodynamic Therapy Based on Nanomaterials.

Photodynamic therapy (PDT) is a noninvasive cancer treatment that requires the copresence of a photosensitizer (PS), oxygen, and light. The efficacy of conventional PDT is usually limited by two factors: delivery of the PS to the tumor and the hypoxic solid tumor environment. To improve the efficacy of PDT, nanomaterial-based, enzyme-assisted PDT (nano-ezPDT), which integrates enzyme-responsive components into nanomedicines, was developed for enhanced PS delivery and oxygen generation. Nano-ezPDT is designed to take full advantage of the catalytic function of locally activated tumor-associated enzymes or smuggled exogeneous enzymes. The enhancement of PS release and accumulation is often controlled by endogenous enzymes upregulated at the tumor sites. Oxygen generation, however, relies mostly on catalase-loaded nanomedicines. In this review, we discuss the associated enzymes, constructs, and types of nanocarriers and highlight the principle and utility of nano-ezPDT for cancer therapy.

Photo-induced reactions for disassembling of coloaded photosensitizer and drug molecules from upconversion-mesoporous silica nanoparticles: An effective synergistic cancer therapy.

Photodynamic therapy is an emerging noninvasive cancer treatment approach, which requires a photosensitizer (PS), light, and molecular oxygen. In this study, we have successfully fabricated a dual nature (pH- and reactive-oxygen-species-responsive) upconversion nanoparticles (UCNPs) to utilize coloaded doxorubicin (DOX) and chlorin e6 (Ce6) with high antitumor efficacy. The model anticancer drug (DOX) and PS (Ce6) were conjugated in a ratio of 1:1 (w:w), and then loaded on the surface of UCNPs@mesoporous silica (mSiO2) (85.63±9.87nm). Cellular uptake could be achieved by either increased permeability or ionic effect of UCNPs@mSiO2, where Ce6 controlled the DOX release under a near-infrared (NIR) laser irradiation at 980nm. A cytotoxicity analysis revealed that the dual-responsive UCNPs@mSiO2 could successfully deliver DOX and Ce6 at the tumor site, causing cell death with a high efficiency. This study shows that the modified UCNPs@mSiO2 is a promising system to realize NIR-light-triggered PS and drug delivery approach to improve synergistic therapies in vitro and in vivo, in the future.

An efficient delivery of photosensitizers and hypoxic prodrugs for a tumor combination therapy by membrane camouflage nanoparticles.

Photodynamic therapy (PDT) is an oxygen-dependent, non-invasive cancer treatment. The hypoxia in the tumor environment limits the therapeutic effects of PDT. The combined delivery of photosensitizers and hypoxic prodrugs is expected to improve the efficacy of tumor treatment. In this paper, an erythrocyte and tumor cell membrane camouflage nanocarrier co-loaded with a photosensitizer (indocyanine green) and a hypoxic prodrug (tirapazamine) were used to combine PDT with chemotherapy. The system achieved less macrophage clearance through erythrocyte membranes and tumor-targeted tumor cell membranes, thereby inducing cell death and increasing tumor environment hypoxia by NIR irradiation of photosensitizers. Furthermore, the hypoxic environment activated TPZ to kill more tumor cells. In vivo results showed that the tumor inhibition rate of the drug-loaded nanoparticles increased from 34% to 64% after membrane modification. Moreover, the tumor inhibition rate of the photodynamic treatment group alone was only 47%, and the tumor inhibition rate after the combination was 1.3 times that of photodynamic therapy alone. Our platform is expected to contribute to the further application of cancer combination therapy.

In vitro toxicity of low-level green laser irradiation effects on human breast cancer cell lines

Laser irradiation therapy on cancer cells is a promising alternative in providing a non-invasive treatment of breast cancer that has a possibility to inhibit cancerous cells selectively without damaging surrounding healthy tissues. This present study aimed to evaluate the effect of the low-level green laser of 532 nm wavelength with various laser power and irradiation time on MCF-7 cancer cell lines. In this work, the MCF-7 cells were seeded to a rate of fifty thousand cells/well in 96-well plate and incubated for 24 h. The cells were then irradiated with the green laser at different power from 0.002 to 0.1 W at 60 s, 540 s, and 900 s duration. The cell viability of the cells was measured by using Alamar Blue assay. From result, the laser irradiation on the cells was able to produce 25-40% inhibition of cell proliferation whereby the untreated cells exhibited a 93% cell viability. It was revealed that high power with longer exposure time increased cell bio-inhibition. Thus, this work using low-power green laser irradiation on cells demonstrated a significant effect on cells and was also demonstrated a promising non-invasive approach that can be used alone or in combination with several other therapies in cancer treatment.

Red blood cell membrane-enveloped O2 self-supplementing biomimetic nanoparticles for tumor imaging-guided enhanced sonodynamic therapy.

Non-invasive sonodynamic therapy (SDT) was developed because of its advantages of high penetration depth and low side effects; however, tumor hypoxia greatly restricts its therapeutic effect. In this study, we aimed to develop ideal O2 self-supplementing nanoparticles for imaging-guided enhanced sonodynamic therapy of tumors with the adept coalescence of biology with nanotechnology.Methods: Based on the natural enzyme system of red blood cells (RBC), biomimetic nanoparticles (QD@P)Rs were fabricated by encapsulating Ag2S quantum dots (QD) in RBC vesicle membranes. The anti-tumor drug PEITC was employed to increase the intracellular H2O2 concentration in tumor cells.Results: In vitro and in vivo experiments demonstrated excellent biocompatibility and prolonged blood circulation of (QD@P)Rs. Following oral administration of PEITC in mice to improve the H2O2 concentration, the enzyme in the nanoprobe catalyzed endogenous H2O2 to increase O2 content and effectively alleviate tumor hypoxia. Triggered by ultrasound under the guidance of fluorescence imaging, (QD@P)Rs generated reactive oxygen species (ROS) to induce tumor cell death, and the increased content of O2 significantly enhanced the effect of SDT.Conclusion: Ag2S QDs were used, for the first time, as a sonosensitizer in the SDT field. In this study, we integrated the advantages of the natural enzyme system and SDT to develop a novel approach for effective non-invasive treatment of cancer.

On the chemiluminescence emission of luminol: protic and aprotic solvents and encapsulation to improve the properties in aqueous solution.

Luminol is a popular molecule that is currently gaining further interest due to its potential role for non-invasive cancer treatments. Design of more efficient derivatives in this context would benefit from a clear knowledge on the origin of the distinct intensity and spectroscopic properties in protic and aprotic solvents observed experimentally, which are still not rationalized. By efficiently combining molecular dynamics, quantum methodologies based on density functional theory and multiconfigurational quantum chemistry and hybrid approaches, and developing herein a computational approach for accurately determining "molar negative extinction (or gain) coefficients of emission", we firstly demonstrate that the amino and imino forms of the 3-aminophthalate dianion are responsible for the chemiluminescence in protic and aprotic medium, respectively. Secondly, we show that the coupling between the adjacent amino and carboxylate groups of luminol existing in aprotic solvents must be kept in aqueous solution to increase the chemiexcitation and emission intensity. Thirdly, modifications of luminol are proposed and simulated showing improved performances as compared to the parent molecule (stronger emission electronic transition and longer emission wavelengths) under the physiological conditions of relevance in biological and medical applications.

Self-Assembled Naphthalimide Conjugated Porphyrin Nanomaterials with D-A Structure for PDT/PTT Synergistic Therapy.

Light-activated phototherapy, including photothermal and photodynamic therapy, has become a new way for spatiotemporal control and noninvasive treatment of cancer. In this study, two new organic porphyrin molecules (NI-Por and NI-ZnPor) with donor (D)-acceptor (A) structure were designed and synthesized. The donor-acceptor pairs facilitated the intermolecular electron transfer, resulting in the enhancement of near-infrared (NIR) absorbance and nonradiative heat generation. After self-assembling, the nanoparticles were formed with the size around 60 nm. Relative to that of organic molecules, the absorption of NI-Por NPs and NI-ZnPor NPs broadened and red-shifted to the near-infrared region. Moreover, the porphyrin-containing nanoparticles can generate heat and reactive oxygen species (ROS) simultaneously induced by a single laser (635 nm). The intracellular reactive oxygen species production of NI-Por NPs and NI-ZnPor NPs was confirmed using DCFH-DA as an indicator. Furthermore, the localization of NI-Por NP and NI-ZnPor NP in HeLa cells was verified by fluorescence confocal laser microscopy. The photocytoxicity of two nanoparticles against HeLa cells was evaluated through the CCK-8 method. The IC50 of NI-Por NPs and NI-ZnPor NPs upon 635 nm laser irradiation was calculated to be 6.92 μg/mL and 5.86 μg/mL, respectively. Furthermore, the PDT/PTT synergistic effect of NPs under a 635 nm laser was verified through different treatment groups in vitro. All these results demonstrated that the as-prepared porphyrin-based nanoparticles are promising nanoagents for PDT/PTT in clinic.