Carbon quantum dots (CQDs) are an emerging research area in the biomedical field due to their biocompatibility and multifunctionality. Herein, we report CQDs synthesized in a green, fast, facile manner in a recyclable mineral oilmediated pyrolysis medium using citric acid as the main carbon source and thiourea as N- and S-doping source. The assynthesized CQDs exhibit excitation-dependent photoemission (Φ = 0.57) with notable energy upconversion behavior at longer wavelengths, suggesting possible utilization in multiphoton microscopy. FT-IR characterization suggest diverse functional groups on the surface which include carboxylic acids, amines, and thiocyanates among others. Photothermal analysis supported the NIR-emissive behavior and showed that CQD solution temperature could potentially increase nearly 20°C higher after 10 min irradiation by 630-nm LED laser source powered at 1 W/cm2. CQDs have been tested in vitro and has been used as multicolor cellular imaging agent.
Carbon quantum dots (CQDs) are an emerging research area in the biomedical field due to their biocompatibility and multifunctionality. Herein, we report CQDs synthesized in a green, fast, facile manner in a recyclable mineral oil-mediated pyrolysis medium using citric acid as the main carbon source and thiourea as N- and S-doping source. The assynthesized CQDs exhibit excitation-dependent photoemission (Φ = 0.57) with notable energy upconversion behavior at longer wavelengths, suggesting possible utilization in multiphoton microscopy. FT-IR characterization suggest diverse functional groups on the surface which include carboxylic acids, amines, and thiocyanates among others. Photothermal analysis supported the NIR-emissive behavior and showed that CQD solution temperature could potentially increase nearly 20°C higher after 10 min irradiation by 630-nm LED laser source powered at 1 W/cm2. CQDs have been tested in vitro and has been used as multicolor cellular imaging agent.
Human squamous cell carcinoma is the major type of oral cancer. Traditional methods for human oral cancers treatments are surgery, chemotherapy and radiotherapy. Because photodynamic therapy is a noninvasive alternative for oral cancer therapy. A novel photosensitizer was first constructed in nanoparticles, for photodynamic therapy. Oncogene silencing RNA was encapsulated into nanoparticles to silence oncogene expression. Two treatments were combined for cancer treatment.Results suggest that the combination therapy could be a potential treatment to develop for human oral cancer in the future.
Cisplatin (CDDP) has been commonly used as a chemotherapeutic drug, mainly used for the treatment of malignant epithelial cell tumors. We have developed a new method based on innovative lipid calcium phosphate, which encapsulated hydrophobic drugs to form liposomal nanoparticles. Esophageal cancer xenograft model was used to investigate the efficacy of liposomal nanoparticles. and it showed good therapeutic efficacy with lower side effects. Liposomal nanoparticles exhibited a better therapeutic effect than that of conventional CDDP.
Small interfering RNA (siRNA) can be used to treat tumor because it can effectively knockdown target oncoprotein expression and it leads to cancer cell death and apoptosis. Hypoxia-inducible factors-1 (HIF-1) is a transcription factor gene. Its high expression of tumor hypoxia cells, activation of transcription factor HIF-1α and angiogenesis found in most cancerous tissues. HIF-1α protein in cancer cells are critical to cell survival, tumor growth and proliferation. Epidermal growth factor receptor (EGFR) gene is another common head and neck oncogene. The dual self-designed siRNA sequences were encapsulated in the lipid-calcium-phosphate (LCP) and targeted to sigma receptors on the surface of cancer cells via binding to amino ethyl anisamide (AEAA). We used human oral cancer cells to establish the xenograft animal model to study the combination therapy for therapeutic results.
Photodynamic therapy is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates tumours oxygen-independent hypoxic conditions. Vascular endothelial growth factor (VEGF) is one of the primary factors that affect tumor angiogenesis. Another emerging treatment to cure cancer is the use of interference RNA to silence a specific mRNA sequence. Such treatment requires a delivery system such as liposomes. The nanoparticle size measured was about 30 nm. Cellular uptake study was performed to verify that the nanoparticles have a sigma receptor mediated pathway. Non-targeted LCP NPs did not show significant difference with or without haloperidol but has a lower intensity as than targeted LCP NPs. These results confirm that LCP NPs have a receptor mediated pathway. Cell viability was found to decrease at 25 nM of transfected VEGF siRNA. Combined therapy of PDT and VEGF siRNA showed significant response as compared with PDT and gene therapy alone. In vivo toxicity assay with mice treated with targeted LCP NPs containing control siRNA or VEGF siRNA and non-targeted LCP NPs containing VEGF siRNA did not show any significant difference with the PBS injected group which suggests that there is no toxicity with the dose. It suggests that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.
The knowledge of manipulating size of biomaterials encapsulated drug into nano-scale particles has been researched and developed in treating cancer. Cancer is the second worldwide cause of death, therefore it is critical to treat cancers challenging with therapeutic modality of various mechanisms. Our preliminary investigation has studied cisplatin encapsulated into lipid-based nanoparticle and examined the therapeutic effect on xenografted animal model. We used mice with tumor volume ranging from 195 to 214 mm3 and then few mice were grouped into three groups including: control (PBS), lipid platinum chloride (LPC) nanoparticles and CDDP (cis-diamminedichloroplatinum(II) at dose of 3mg cisplatin /kg body weight. The effect of the treatment was observed for 12 days post-injection. It showed that LPC NPs demonstrated a better therapeutic effect compared to CDDP at same 3mg cisplatin/kg drug dose of tumor size reduction, 96.6% and 11.1% respectively. In addition, mouse body weight loss of LPC, CDDP and PBS treated group are 12.1%, 24.3% and 1.4%. It means that by compared to CDDP group, LPC group demonstrated less side effect as not much reduction of body weight have found. Our findings have shown to be a potential modality to further investigate as a feasible cancer therapy modality.
The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.
The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.
Vascular endothelial growth factor A (VEGF-A), commonly known as VEGF, is one of the primary factors that affect tumor angiogenesis. It was found to be expressed in cancer cell lines including oral squamous cell carcinoma. Photodynamic therapy (PDT) is a novel therapeutic modality to treat cancer by using a photosensitizer which is activated by a light source to produce reactive oxygen species and mediates oxygen-independent hypoxic conditions to tumor. Another emerging treatment to cure cancer is the use of interference RNA (e.g. siRNA) to silence a specific mRNA sequence. VEGF-A was found to be expressed in oral squamous cell carcinoma and overexpressed after 24 hour post-PDT by Western blot analysis. Cell viability was found to decrease at 25 nM of transfected VEGF-A siRNA. In vitro combined therapy of PDT and VEGF-A siRNA showed better response as compared with PDT and gene therapy alone. The results suggest that PDT combined with targeted gene therapy has a potential mean to achieve better therapeutic outcome.
Oral cancer has becomes the most prominent male cancer disease due to the local
betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order
to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study
was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced
hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal
pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were
induced and proven by histological examination. These DMBA-induced cancerous
lesions were used for testing the efficacy of topical ALA -mediated PDT. We found
that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical
application of ALA gel. The precancerous lesions in hamsters were then treated with
topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED
635 nm Wonderlight device. It is suggesting that optimization of the given light dose
is critical to the success of PDT results.
In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the
betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of
people. In order to eliminate the systemic phototoxic effect of
5-aminolevulinic acid
(ALA), this study was designed to use a topical ALA-mediated PDT for treatment of
DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to
one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous
lesions were induced and proven by histological examination. These DMBA-induced
cancerous lesions were used for testing the efficacy of topical
ALA-mediated PDT.
Before PDT, fluorescence spectroscopy was used to determine when ALA reached its
peak level in the lesional epithelial cells after topical application of ALA gel. We
found that ALA reached its peak level in precancerous lesions about 2.5 hrs after
topical application of ALA gel. The cancerous lesions in hamsters were then treated
with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED
635 nm fiber-guided light device. Visual examination demonstrated that adjuvant
topical ALA -mediated PDT group has shown better therapeutic results in compared
to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced
hamster buccal pouch precancerous lesions.
Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is
the betel nut chewing habit combing with smoking and
alcohol-drinking lifestyle of people results in
oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In
previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated
effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic
effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of
DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal
pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven
by histological examination. These DMBA-induced cancerous lesions were used for testing the
efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to
determine when photosan reached its peak level in the lesional epithelial cells after topical
application of photosan gel. We found that photosan reached its peak level in cancerous lesions
about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were
then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose
200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination
demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced
hamster buccal pouch cancerous lesions.
In Taiwan, oral cancer has become a prominent cancer because of its highest annual increase rate among all cancer diseases. Betel quid chewing habit is a major risk factor for oral precancerous and cancerous lesions and there are more than two million people who have this habit in Taiwan. Our previous studies showed that chlorophyll-pheophytin derivative (CPD)-mediated PDT is very effective for killing of SCC-4 cell lines in vitro. In order to decrease the systemic phototoxic effect of CPD, this study was designed to use a topical CPD-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions of moderate to severe dysplasia were induced and proven by histological examination. These induced precancerous lesions were used for testing the efficacy of topical CPD-mediated PDT.
Before PDT, fluorescence spectroscopy was used to determine when CPD reached its peak level in the lesional epithelial cells after topical application of CPD gel. We found that CPD reached its peak level in precancerous lesions about 1 hour (range, 0 to 30 hours) after topical application of CPD gel. The precancerous lesions in hamsters were then treated with topical CPD-mediated PDT (fluence rate: 200 mW/cm2; light exposure dose 100 J/cm2) using the portable WonderLight LED 635 nm fiber-guided light device once or twice a week. Visual and histological examination demonstrated that topical CPD-mediated PDT was partially effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.
KEYWORDS: Photodynamic therapy, Light emitting diodes, Light sources, Cancer, Toxicity, Minerals, Tissues, Photomicroscopy, In vivo imaging, Control systems
One of the best strategies to prevent the occurrence of oral cancer is to eliminate oral precancers and block their further
malignant transformation. Previous studies showed that
photosan-mediated photodynamic therapy (photosan-PDT) is
very effective for human head and neck cancers. To avoid the systemic photodynamic toxicity of photosan, this study
was designed to use a topical photosan-PDT for treatment of
DMBA-induced hamster buccal pouch precancerous
lesions. Twelve 10-week-old male Syrian golden hamsters were used in this study. DMBA was applied to the left buccal
pouches thrice a week for 8 to 10 weeks and mineral oil was painted on the right buccal pouches thrice a week for 8 to
10 weeks as the normal controls. Six hamsters were euthanized for tissue harvest. Precancerous lesions of moderate to
severe dysplasia were consistently induced and proven by histological examination. These induced precancerous lesions
in the remaining 6 hamsters were used for testing the efficacy of topical photosan-PDT. Before PDT, fluorescence
spectroscopy was used to determine when protoporphyrine IX (PpIX) reached its peak level in the lesional epithelial
cells after topical application of photosan-gel. We found that PpIX reached its peak level in precancerous lesions about
13.5 min after topical application of photosan-gel. The precancerous lesions in 4 hamsters were treated with topical
photosan-PDT using the 635-nm LED light once or twice a week. Complete regression of the precancerous lesions was
found after 2-4 PDT treatments by visual and histological examination. Our findings indicate that topical photosan-PDT
is a very effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.
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