Dr Sukanta Kamila - Academia.edu (original) (raw)
Papers by Dr Sukanta Kamila
![Research paper thumbnail of Determination of zinc in aqueous solution using CdSe/ZnS quantum dots functionalised with [carboxymethyl-(4-mercapto-phenyl)-amino]-acetate](https://attachments.academia-assets.com/118720227/thumbnails/1.jpg)
](International Journal of Biomedical Nanoscience and Nanotechnology, 2011
CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displ... more CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displayed selectivity for Zn 2+ ion when tested against a range of other commonly available metal ions in buffered aqueous solution (pH 7.0 ± 0.1). The probe displayed an enhancement in its fluorescence intensity upon addition of Zn 2+ attributed to a cancellation of a photoinduced electron transfer process from the bound receptor to the excited quantum dot that otherwise led to non-radiative decay. Good linearity was established for Zn 2+ in the 0.2 to 5.0 mM range.
Journal of Fluorescence, Dec 20, 2007
A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-th... more A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-thiourea in the fluorophore-spacer-receptor format typical of Photoinduced Electron Transfer (PET) based organic dye sensors. The resulting QD conjugate was tested for selectivity toward the tetrabutylammonium salts of fluoride, chloride, bromide, hydrogen sulfate and acetate. Addition of fluoride, chloride and acetate ions resulted in an approximate 90% quenching of the original fluorescence intensity, while bromide and hydrogen sulfate had almost no effect. The observed quench was attributed to an increase in the reduction potential of the receptor upon anion binding resulting in an increase in PET from the excited QD to the receptor and a concomitant reduction in fluorescence intensity. The selectivity and sensitivity were comparable to an analagous organic dye based sensor where a similar receptor was bound to an anthracene fluorophore. Thus a modular approach is evident where a receptor used in an organic dye based sensor can be adapted and successfully used with QD's.
The Journal of the Acoustical Society of America
Ultrasound, microbubbles, and magnetic nanoparticles have been used both separately and in varyin... more Ultrasound, microbubbles, and magnetic nanoparticles have been used both separately and in varying combinations for targeted drug delivery. Recent studies have demonstrated the therapeutic benefit of magnetic microbubble (MMB) retention and acoustic targeting using separate devices. As a developmental step towards clinical implementation, a magnetic-acoustic device (MAD) was designed for the purpose of generating co-aligned magnetic and acoustic fields with a single hand-held enclosure. This paper presents in vitro characterization and in vivo demonstration of a targeted therapeutic system wherein the MAD non-invasively retains and activates drug-loaded MMBs. Free field experiments were conducted in order to characterize the magnetic field and its gradient for MMB capture, and to quantify acoustic field strength and directivity. Flow phantom experiments were used to quantify MMB retention and illustrate the resulting enhancement of cavitation activity. Murine experiments then demons...
Ultrasound in Medicine & Biology, 2021
In this study we compared three different microbubble-based approaches for the delivery of a wide... more In this study we compared three different microbubble-based approaches for the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration of gemcitabine and microbubbles (Gem+MB), (ii) conjugates of microbubbles and gemcitabine-loaded liposomes (GemlipoMB), and (iii) microbubbles with gemcitabine directly bound to their surfaces (GembioMB). Both in vitro and in vivo investigations were carried out, respectively in the RT112 bladder cancer cell line and a murine orthotopic muscle-invasive bladder cancer model. The in vitro (in vivo) ultrasound exposure conditions were 1 (1.1) MHz centre frequency, 0.07 (1.0) MPa peak negative pressure, 3000 (20000) cycles and 100 (0.5) Hz pulse repetition frequency. Ultrasound exposure produced no significant increase in drug uptake either in vitro or in vivo compared with the drug-only control for co-administered gemcitabine and microbubbles. In vivo, GemlipoMB prolonged the plasma circulation time of gemcitabine, but only GembioMB produced a statistically significant increase in cleaved caspase 3 expression in the tumor, indicative of gemcitabine-induced apoptosis.
Journal of Controlled Release, 2021
Treatment options for patients with pancreatic cancer are limited and survival prospects have bar... more Treatment options for patients with pancreatic cancer are limited and survival prospects have barely changed over the past 4 decades. Chemoradiation treatment (CRT) has been used as neoadjuvant therapy in patients with borderline resectable disease to reduce tumour burden and increase the proportion of patients eligible for surgery. Antimetabolite drugs such as gemcitabine and 5-fluorouracil are known to sensitise pancreatic tumours to radiation treatment. Likewise, photodynamic therapy (PDT) has also been shown to enhance the effect of radiation therapy. However, PDT is limited to treating superficial lesions due to the attenuation of light by tissue. The ability of the related technique, sonodynamic therapy (SDT), to enhance CRT was investigated in two murine models of pancreatic cancer (PSN-1 and BxPC-3) in this study. SDT uses low intensity ultrasound to activate an otherwise non-toxic sensitiser, generating toxic levels of reactive oxygen species (ROS) locally. It is applicable to greater target depths than PDT due to the ability of ultrasound to propagate further than light in tissue. Both CRT and the combination of CRT plus SDT delayed tumour growth in the two tumour models. In the PSN-1 model, but not the BxPC-3 model, the combination treatment caused an increase in survival relative to CRT alone (p = 0.038). The improvement in survival conferred by the addition of SDT in this model may be related to differences in tumour architecture between the two models. MRI and US images showed that PSN-1 tumours were less well perfused and vascularised than BxPC-3 tumours. This poor vascularisation may explain why PSN-1 tumours were more susceptible to the effects of vascular damage exerted by SDT treatment.
International Journal of Radiation Oncology*Biology*Physics, 2021
Purpose: Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC).... more Purpose: Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC). Although agents such as gemcitabine can enhance tumor radiosensitivity, their side effects can limit patient eligibility and treatment efficacy. This study investigates ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal-tissue toxicity in a murine orthotopic MIBC model. Materials and Methods: CD1-nude mice were injected orthotopically with RT112 bladder tumor cells. Conventional chemoradiation involved injecting gemcitabine (10 mg/kg) before 6 Gy targeted irradiation of the bladder area using the Small Animal Radiation Research Platform (SARRP). Ultrasound-mediated gemcitabine delivery (10 mg/kg gemcitabine) involved either coadministration of microbubbles with gemcitabine or conjugating gemcitabine onto microbubbles followed by exposure to ultrasound (1.1 MHz center frequency, 1 MPa peak negative pressure, 1% duty cycle, and 0.5 Hz pulse repetition frequency) before SARRP irradiation. The effect of ultrasound and microbubbles alone was also tested. Tumor volumes were
European Journal of Pharmaceutics and Biopharmaceutics, 2019
Mastectomy is common surgical treatment used in the management of breast cancer but has associate... more Mastectomy is common surgical treatment used in the management of breast cancer but has associated physical and psychological consequences for the patient. Breast conservation surgery (BCS) is an alternative to mastectomy but is only possible when the tumour is of an appropriate size. Neo-adjuvant chemotherapy has been successfully used to downstage tumours and increase the number of patients eligible for BCS. However, the chemotherapies used in this approach are non-targeted and often result in significant side effects to the patient. In this manuscript, we evaluate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver Rose Bengal-mediated sonodynamic therapy (SDT) in combination with paclitaxel (PTX) and doxorubicin (Dox) chemotherapy as a potential treatment for breast cancer. Efficacy of the combined treatment was determined in a threedimensional (3D) spheroid model of human breast cancer and in a murine model of the disease bearing subcutaneous MCF-7 tumours. The results demonstrated a significant reduction in both the cell viability of spheroids and tumour volume following treatment with the drug loaded microbubbles and ultrasound compared to targets treated with the drug loaded microbubbles alone or a Cremophor EL suspension of PTX and Dox. In addition, the weight of animals that received the microbubble treatment was unchanged throughout the study while a reduction of 12.1% was observed for animals treated with a Cremophor suspension of PTX/Dox. These results suggest that UTMD-mediated chemo-sonodynamic therapy is an efficacious and well tolerated approach for the treatment of breast cancer.
Langmuir, 2018
Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast ... more Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. While the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesized inhouse to directly observe its distribution in the microbubble coating. We examined microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was observed only on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. "Squeezing out" of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37°C, however, the stability in serum was found to be the same for both formulations, and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.
Journal of controlled release : official journal of the Controlled Release Society, Jan 11, 2018
Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1... more Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (OMB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to OMBs (OMB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the OMB-Gem and a Rose Bengal loaded OMB (OMB-RB) as a ...
Biomaterials, Jan 26, 2015
In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform fo... more In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1), cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the...
Colloidal Nanoparticles for Biomedical Applications X, 2015
Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a C... more Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a CQD-protoporphyrin IX (CQD-PPIX) conjugate to folate receptor positive (FR+) HeLa cells for use in two-photon excited Photodynamic Therapy (TPE-PDT). FA was covalently attached to the CQD-PPIX conjugate to form a FA-CQD-PPIX conjugate. The uptake of the FA-CQD-PPIX conjugate in FR+ HeLa cells was shown to be 7 times greater than the CQD-PPIX conjugate, while both conjugates showed a similar uptake in FR negative (FR-) HT-47 cells. TPE-PDT experiments, using HeLa cells as a target, revealed a 30% improved cytotoxicity for cells treated with the FA-CQD-PPIX conjugate and TPE compared to controls treated with the CQD-PPIX conjugate and TPE. Collectively, these results suggest the presence of FA can facilitate targeting of CQD-sensitiser conjugates to FR+ cells resulting in an improved PDT effect.
![Research paper thumbnail of ChemInform Abstract: Application of Directed Metalation in Synthesis. Part 2. An Expedient Synthesis of Methoxybenzo[b]thiophenes](https://attachments.academia-assets.com/118720226/thumbnails/1.jpg)
](ChemInform, 2010
Application of Directed Metalation in Synthesis. Part 2. An Expedient Synthesis of Methoxybenzo[b... more Application of Directed Metalation in Synthesis. Part 2. An Expedient Synthesis of Methoxybenzo[b]thiophenes.-Direct ortho-lithiation of benzamides [cf. (I)] followed by a cyclization-reduction sequence provides a short and simple synthesis of the title compounds.
![Research paper thumbnail of Studies in Sulfur Heterocycles.Part 16:Synthesis of [1]Benzothieno[3,2- b ]pyrans via Tandem Reactionsfrom 2,3-Dihydrobenzo[ b ]thiophene-3(2 H )ones](https://attachments.academia-assets.com/118720261/thumbnails/1.jpg)
](Synlett, 2003
Benzothiophene derivatives Benzothiophene derivatives R 0100 Studies in Sulfur Heterocycles. Part... more Benzothiophene derivatives Benzothiophene derivatives R 0100 Studies in Sulfur Heterocycles. Part 16. Synthesis of [1]Benzothieno[3,2-b]pyrans via Tandem Reactions from 2,3-Dihydrobenzo[b]thiophene-3(2H)ones.-Thermolysis of the exo-methylene 2,3-dihydro-benzothiophenones (III) results in electrocyclic ring closure to give benzothienopyrans. A similar compound (IX) is obtained from the amide (Ib) and crotonaldehyde in the presence of LDA directly.-(
Journal of Fluorescence, 2007
A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-th... more A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-thiourea in the fluorophore-spacer-receptor format typical of Photoinduced Electron Transfer (PET) based organic dye sensors. The resulting QD conjugate was tested for selectivity toward the tetrabutylammonium salts of fluoride, chloride, bromide, hydrogen sulfate and acetate. Addition of fluoride, chloride and acetate ions resulted in an approximate 90% quenching of the original fluorescence intensity, while bromide and hydrogen sulfate had almost no effect. The observed quench was attributed to an increase in the reduction potential of the receptor upon anion binding resulting in an increase in PET from the excited QD to the receptor and a concomitant reduction in fluorescence intensity. The selectivity and sensitivity were comparable to an analagous organic dye based sensor where a similar receptor was bound to an anthracene fluorophore. Thus a modular approach is evident where a receptor used in an organic dye based sensor can be adapted and successfully used with QD's.
![Research paper thumbnail of Determination of zinc in aqueous solution using CdSe/ZnS quantum dots functionalised with [carboxymethyl-(4-mercapto-phenyl)-amino]-acetate](https://attachments.academia-assets.com/118720231/thumbnails/1.jpg)
](International Journal of Biomedical Nanoscience and Nanotechnology, 2011
CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displ... more CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displayed selectivity for Zn 2+ ion when tested against a range of other commonly available metal ions in buffered aqueous solution (pH 7.0 ± 0.1). The probe displayed an enhancement in its fluorescence intensity upon addition of Zn 2+ attributed to a cancellation of a photoinduced electron transfer process from the bound receptor to the excited quantum dot that otherwise led to non-radiative decay. Good linearity was established for Zn 2+ in the 0.2 to 5.0 mM range.
Chemical Communications, 2017
Iodinated cyanine dye 6a has been developed for use as a NIR excited photosensitiser in photodyna... more Iodinated cyanine dye 6a has been developed for use as a NIR excited photosensitiser in photodynamic therapy.
![Research paper thumbnail of Synthetic studies in sulfur heterocycles. One-pot synthesis of “thioaurones” and their conversion into [1]benzothieno[3,2-b]pyrans via tandem reactions](https://attachments.academia-assets.com/101302982/thumbnails/1.jpg)
](Arkivoc, 2005
Thioaurones were prepared one pot in high yield by the treatment of N,N-diethyl-2-(methylsulfanyl... more Thioaurones were prepared one pot in high yield by the treatment of N,N-diethyl-2-(methylsulfanyl)arylamides with LDA and an aromatic aldehyde through directed orthometalation. Heating the thioaurones derived from cinnamaldehyde above 200 ºC resulted in [1]benzothieno[3,2-b]pyrans. Treatment of N,N-diethyl-2-(methylsulfanyl)benzamide and crotonaldehyde gave 4-(methylsulfanyl)benzothieno[3,2,-b]pyran via conjugate nucleophilic addition and ring closure in one pot. A possible mechanistic pathway is discussed.
New Journal of Chemistry, 2018
A ratiometric polymeric fluorescent probe for Zn(ii) was developed capable of measuring Zn(ii) co... more A ratiometric polymeric fluorescent probe for Zn(ii) was developed capable of measuring Zn(ii) concentrations in aqueous solution between 0 and 5 mM and was also capable of discriminating between resting and high Zn(ii) levels in living cells using confocal fluorescence microscopy.
Journal of controlled release : official journal of the Controlled Release Society, Jan 29, 2017
Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipi... more Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be signific...
International Journal of Biomedical Nanoscience and Nanotechnology, 2011
CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displ... more CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displayed selectivity for Zn 2+ ion when tested against a range of other commonly available metal ions in buffered aqueous solution (pH 7.0 ± 0.1). The probe displayed an enhancement in its fluorescence intensity upon addition of Zn 2+ attributed to a cancellation of a photoinduced electron transfer process from the bound receptor to the excited quantum dot that otherwise led to non-radiative decay. Good linearity was established for Zn 2+ in the 0.2 to 5.0 mM range.
Journal of Fluorescence, Dec 20, 2007
A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-th... more A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-thiourea in the fluorophore-spacer-receptor format typical of Photoinduced Electron Transfer (PET) based organic dye sensors. The resulting QD conjugate was tested for selectivity toward the tetrabutylammonium salts of fluoride, chloride, bromide, hydrogen sulfate and acetate. Addition of fluoride, chloride and acetate ions resulted in an approximate 90% quenching of the original fluorescence intensity, while bromide and hydrogen sulfate had almost no effect. The observed quench was attributed to an increase in the reduction potential of the receptor upon anion binding resulting in an increase in PET from the excited QD to the receptor and a concomitant reduction in fluorescence intensity. The selectivity and sensitivity were comparable to an analagous organic dye based sensor where a similar receptor was bound to an anthracene fluorophore. Thus a modular approach is evident where a receptor used in an organic dye based sensor can be adapted and successfully used with QD's.
The Journal of the Acoustical Society of America
Ultrasound, microbubbles, and magnetic nanoparticles have been used both separately and in varyin... more Ultrasound, microbubbles, and magnetic nanoparticles have been used both separately and in varying combinations for targeted drug delivery. Recent studies have demonstrated the therapeutic benefit of magnetic microbubble (MMB) retention and acoustic targeting using separate devices. As a developmental step towards clinical implementation, a magnetic-acoustic device (MAD) was designed for the purpose of generating co-aligned magnetic and acoustic fields with a single hand-held enclosure. This paper presents in vitro characterization and in vivo demonstration of a targeted therapeutic system wherein the MAD non-invasively retains and activates drug-loaded MMBs. Free field experiments were conducted in order to characterize the magnetic field and its gradient for MMB capture, and to quantify acoustic field strength and directivity. Flow phantom experiments were used to quantify MMB retention and illustrate the resulting enhancement of cavitation activity. Murine experiments then demons...
Ultrasound in Medicine & Biology, 2021
In this study we compared three different microbubble-based approaches for the delivery of a wide... more In this study we compared three different microbubble-based approaches for the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration of gemcitabine and microbubbles (Gem+MB), (ii) conjugates of microbubbles and gemcitabine-loaded liposomes (GemlipoMB), and (iii) microbubbles with gemcitabine directly bound to their surfaces (GembioMB). Both in vitro and in vivo investigations were carried out, respectively in the RT112 bladder cancer cell line and a murine orthotopic muscle-invasive bladder cancer model. The in vitro (in vivo) ultrasound exposure conditions were 1 (1.1) MHz centre frequency, 0.07 (1.0) MPa peak negative pressure, 3000 (20000) cycles and 100 (0.5) Hz pulse repetition frequency. Ultrasound exposure produced no significant increase in drug uptake either in vitro or in vivo compared with the drug-only control for co-administered gemcitabine and microbubbles. In vivo, GemlipoMB prolonged the plasma circulation time of gemcitabine, but only GembioMB produced a statistically significant increase in cleaved caspase 3 expression in the tumor, indicative of gemcitabine-induced apoptosis.
Journal of Controlled Release, 2021
Treatment options for patients with pancreatic cancer are limited and survival prospects have bar... more Treatment options for patients with pancreatic cancer are limited and survival prospects have barely changed over the past 4 decades. Chemoradiation treatment (CRT) has been used as neoadjuvant therapy in patients with borderline resectable disease to reduce tumour burden and increase the proportion of patients eligible for surgery. Antimetabolite drugs such as gemcitabine and 5-fluorouracil are known to sensitise pancreatic tumours to radiation treatment. Likewise, photodynamic therapy (PDT) has also been shown to enhance the effect of radiation therapy. However, PDT is limited to treating superficial lesions due to the attenuation of light by tissue. The ability of the related technique, sonodynamic therapy (SDT), to enhance CRT was investigated in two murine models of pancreatic cancer (PSN-1 and BxPC-3) in this study. SDT uses low intensity ultrasound to activate an otherwise non-toxic sensitiser, generating toxic levels of reactive oxygen species (ROS) locally. It is applicable to greater target depths than PDT due to the ability of ultrasound to propagate further than light in tissue. Both CRT and the combination of CRT plus SDT delayed tumour growth in the two tumour models. In the PSN-1 model, but not the BxPC-3 model, the combination treatment caused an increase in survival relative to CRT alone (p = 0.038). The improvement in survival conferred by the addition of SDT in this model may be related to differences in tumour architecture between the two models. MRI and US images showed that PSN-1 tumours were less well perfused and vascularised than BxPC-3 tumours. This poor vascularisation may explain why PSN-1 tumours were more susceptible to the effects of vascular damage exerted by SDT treatment.
International Journal of Radiation Oncology*Biology*Physics, 2021
Purpose: Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC).... more Purpose: Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC). Although agents such as gemcitabine can enhance tumor radiosensitivity, their side effects can limit patient eligibility and treatment efficacy. This study investigates ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal-tissue toxicity in a murine orthotopic MIBC model. Materials and Methods: CD1-nude mice were injected orthotopically with RT112 bladder tumor cells. Conventional chemoradiation involved injecting gemcitabine (10 mg/kg) before 6 Gy targeted irradiation of the bladder area using the Small Animal Radiation Research Platform (SARRP). Ultrasound-mediated gemcitabine delivery (10 mg/kg gemcitabine) involved either coadministration of microbubbles with gemcitabine or conjugating gemcitabine onto microbubbles followed by exposure to ultrasound (1.1 MHz center frequency, 1 MPa peak negative pressure, 1% duty cycle, and 0.5 Hz pulse repetition frequency) before SARRP irradiation. The effect of ultrasound and microbubbles alone was also tested. Tumor volumes were
European Journal of Pharmaceutics and Biopharmaceutics, 2019
Mastectomy is common surgical treatment used in the management of breast cancer but has associate... more Mastectomy is common surgical treatment used in the management of breast cancer but has associated physical and psychological consequences for the patient. Breast conservation surgery (BCS) is an alternative to mastectomy but is only possible when the tumour is of an appropriate size. Neo-adjuvant chemotherapy has been successfully used to downstage tumours and increase the number of patients eligible for BCS. However, the chemotherapies used in this approach are non-targeted and often result in significant side effects to the patient. In this manuscript, we evaluate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver Rose Bengal-mediated sonodynamic therapy (SDT) in combination with paclitaxel (PTX) and doxorubicin (Dox) chemotherapy as a potential treatment for breast cancer. Efficacy of the combined treatment was determined in a threedimensional (3D) spheroid model of human breast cancer and in a murine model of the disease bearing subcutaneous MCF-7 tumours. The results demonstrated a significant reduction in both the cell viability of spheroids and tumour volume following treatment with the drug loaded microbubbles and ultrasound compared to targets treated with the drug loaded microbubbles alone or a Cremophor EL suspension of PTX and Dox. In addition, the weight of animals that received the microbubble treatment was unchanged throughout the study while a reduction of 12.1% was observed for animals treated with a Cremophor suspension of PTX/Dox. These results suggest that UTMD-mediated chemo-sonodynamic therapy is an efficacious and well tolerated approach for the treatment of breast cancer.
Langmuir, 2018
Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast ... more Phospholipid coated microbubbles are currently in widespread clinical use as ultrasound contrast agents and under investigation for therapeutic applications. Previous studies have demonstrated the importance of the coating nanostructure in determining microbubble stability and its dependence upon both composition and processing method. While the influence of different phospholipids has been widely investigated, the role of other constituents such as emulsifiers has received comparatively little attention. Herein, we present an examination of the impact of polyethylene glycol (PEG) derivatives upon microbubble structure and properties. We present data using both pegylated phospholipids and a fluorescent PEG-40-stearate analogue synthesized inhouse to directly observe its distribution in the microbubble coating. We examined microbubbles of clinically relevant sizes, investigating both their surface properties and population size distribution and stability. Domain formation was observed only on the surface of larger microbubbles, which were found to contain a higher concentration of PEG-40-stearate. Lipid analogue dyes were also found to influence domain formation compared with PEG-40-stearate alone. "Squeezing out" of PEG-40-stearate was not observed from any of the microbubble sizes investigated. At ambient temperature, microbubbles formulated with DSPE-PEG(2000) were found to be more stable than those containing PEG-40-stearate. At 37°C, however, the stability in serum was found to be the same for both formulations, and no difference in acoustic backscatter was detected. This could potentially reduce the cost of PEGylated microbubbles and facilitate simpler attachment of targeting or therapeutic species. However, whether PEG-40-stearate sufficiently shields microbubbles to inhibit physiological clearance mechanisms still requires investigation.
Journal of controlled release : official journal of the Controlled Release Society, Jan 11, 2018
Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1... more Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (OMB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to OMBs (OMB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the OMB-Gem and a Rose Bengal loaded OMB (OMB-RB) as a ...
Biomaterials, Jan 26, 2015
In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform fo... more In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1), cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the...
Colloidal Nanoparticles for Biomedical Applications X, 2015
Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a C... more Folic acid (FA) has been used as a molecular targeting strategy to improve the specificity of a CQD-protoporphyrin IX (CQD-PPIX) conjugate to folate receptor positive (FR+) HeLa cells for use in two-photon excited Photodynamic Therapy (TPE-PDT). FA was covalently attached to the CQD-PPIX conjugate to form a FA-CQD-PPIX conjugate. The uptake of the FA-CQD-PPIX conjugate in FR+ HeLa cells was shown to be 7 times greater than the CQD-PPIX conjugate, while both conjugates showed a similar uptake in FR negative (FR-) HT-47 cells. TPE-PDT experiments, using HeLa cells as a target, revealed a 30% improved cytotoxicity for cells treated with the FA-CQD-PPIX conjugate and TPE compared to controls treated with the CQD-PPIX conjugate and TPE. Collectively, these results suggest the presence of FA can facilitate targeting of CQD-sensitiser conjugates to FR+ cells resulting in an improved PDT effect.
ChemInform, 2010
Application of Directed Metalation in Synthesis. Part 2. An Expedient Synthesis of Methoxybenzo[b... more Application of Directed Metalation in Synthesis. Part 2. An Expedient Synthesis of Methoxybenzo[b]thiophenes.-Direct ortho-lithiation of benzamides [cf. (I)] followed by a cyclization-reduction sequence provides a short and simple synthesis of the title compounds.
Synlett, 2003
Benzothiophene derivatives Benzothiophene derivatives R 0100 Studies in Sulfur Heterocycles. Part... more Benzothiophene derivatives Benzothiophene derivatives R 0100 Studies in Sulfur Heterocycles. Part 16. Synthesis of [1]Benzothieno[3,2-b]pyrans via Tandem Reactions from 2,3-Dihydrobenzo[b]thiophene-3(2H)ones.-Thermolysis of the exo-methylene 2,3-dihydro-benzothiophenones (III) results in electrocyclic ring closure to give benzothienopyrans. A similar compound (IX) is obtained from the amide (Ib) and crotonaldehyde in the presence of LDA directly.-(
Journal of Fluorescence, 2007
A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-th... more A CdSe-ZnS quantum dot (QD) has been surface functionalised with 1-(2-mercapto-ethyl)-3-phenyl-thiourea in the fluorophore-spacer-receptor format typical of Photoinduced Electron Transfer (PET) based organic dye sensors. The resulting QD conjugate was tested for selectivity toward the tetrabutylammonium salts of fluoride, chloride, bromide, hydrogen sulfate and acetate. Addition of fluoride, chloride and acetate ions resulted in an approximate 90% quenching of the original fluorescence intensity, while bromide and hydrogen sulfate had almost no effect. The observed quench was attributed to an increase in the reduction potential of the receptor upon anion binding resulting in an increase in PET from the excited QD to the receptor and a concomitant reduction in fluorescence intensity. The selectivity and sensitivity were comparable to an analagous organic dye based sensor where a similar receptor was bound to an anthracene fluorophore. Thus a modular approach is evident where a receptor used in an organic dye based sensor can be adapted and successfully used with QD's.
International Journal of Biomedical Nanoscience and Nanotechnology, 2011
CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displ... more CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displayed selectivity for Zn 2+ ion when tested against a range of other commonly available metal ions in buffered aqueous solution (pH 7.0 ± 0.1). The probe displayed an enhancement in its fluorescence intensity upon addition of Zn 2+ attributed to a cancellation of a photoinduced electron transfer process from the bound receptor to the excited quantum dot that otherwise led to non-radiative decay. Good linearity was established for Zn 2+ in the 0.2 to 5.0 mM range.
Chemical Communications, 2017
Iodinated cyanine dye 6a has been developed for use as a NIR excited photosensitiser in photodyna... more Iodinated cyanine dye 6a has been developed for use as a NIR excited photosensitiser in photodynamic therapy.
Arkivoc, 2005
Thioaurones were prepared one pot in high yield by the treatment of N,N-diethyl-2-(methylsulfanyl... more Thioaurones were prepared one pot in high yield by the treatment of N,N-diethyl-2-(methylsulfanyl)arylamides with LDA and an aromatic aldehyde through directed orthometalation. Heating the thioaurones derived from cinnamaldehyde above 200 ºC resulted in [1]benzothieno[3,2-b]pyrans. Treatment of N,N-diethyl-2-(methylsulfanyl)benzamide and crotonaldehyde gave 4-(methylsulfanyl)benzothieno[3,2,-b]pyran via conjugate nucleophilic addition and ring closure in one pot. A possible mechanistic pathway is discussed.
New Journal of Chemistry, 2018
A ratiometric polymeric fluorescent probe for Zn(ii) was developed capable of measuring Zn(ii) co... more A ratiometric polymeric fluorescent probe for Zn(ii) was developed capable of measuring Zn(ii) concentrations in aqueous solution between 0 and 5 mM and was also capable of discriminating between resting and high Zn(ii) levels in living cells using confocal fluorescence microscopy.
Journal of controlled release : official journal of the Controlled Release Society, Jan 29, 2017
Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipi... more Magnetically responsive microbubbles (MagMBs), consisting of an oxygen gas core and a phospholipid coating functionalised with Rose Bengal (RB) and/or 5-fluorouracil (5-FU), were assessed as a delivery vehicle for the targeted treatment of pancreatic cancer using combined antimetabolite and sonodynamic therapy (SDT). MagMBs delivering the combined 5-FU/SDT treatment produced a reduction in cell viability of over 50% when tested against a panel of four pancreatic cancer cell lines in vitro. Intravenous administration of the MagMBs to mice bearing orthotopic human xenograft BxPC-3 tumours yielded a 48.3% reduction in tumour volume relative to an untreated control group (p<0.05) when the tumour was exposed to both external magnetic and ultrasound fields during administration of the MagMBs. In contrast, application of an external ultrasound field alone resulted in a 27% reduction in tumour volume. In addition, activated caspase and BAX protein levels were both observed to be signific...