Jia Lin

Deakin University, Geelong, Victoria, Australia

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Publications (16)46.76 Total impact

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    ABSTRACT: Insufficient penetration of therapeutic agents into tumor tissues results in inadequate drug distribution and lower intracellular concentration of drugs, leading to the increase of drug resistance and resultant failure of cancer treatment. Targeted drug delivery to solid tumors followed by complete drug penetration and durable retention will significantly improve clinical outcomes of cancer therapy. Monoclonal antibodies have been commonly used in clinic for cancer treatment, but their limitation of penetrating into tumor tissues still remains because of their large size. Aptamers, as “chemical antibodies”, are 15-20 times smaller than antibodies. To explore whether aptamers are superior to antibodies in terms of tumor penetration, we carried out the first comprehensive study to compare the performance of an EpCAM aptamer with an EpCAM antibody in theranostic applications. Penetration and retention were studied in in vitro three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal cancer xenograft model. We found that the EpCAM aptamer can not only effectively penetrate into the tumorsphere cores but can also be retained by tumor sphere cells for at least 24 h, while limited tumor penetration by EpCAM antibody was observed after 4 h incubation. As observed from in vivo live animal imaging, EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a rapid clearance after 80 min, while the signal of peak uptake and disappearance of antibody appeared at 3 h and 6 h after intravenous injection, respectively. The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26 h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft tumors than that of antibody, at 3 h and 24 h after intravenous administration, respectively. In addition, the aptamer achieved at least a 4-time better tumor penetration in xenograft tumours than that of the antibody at a 200 μm distances from the blood vessels 3 h after intravenous injection. Taken together, these data indicate that aptmers are superior to antibodies in cancer theranostics due to their better tumor penetration, more homogeneous distribution and longer retention in tumor sites. Thus, aptamers are promising agents for targeted tumor therapeutics and molecular imaging.
    Theranostics 12/2015; · 7.83 Impact Factor
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    ABSTRACT: As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.
    PLoS ONE 09/2014; 9(7):e103736. DOI:10.1371/journal.pone.0103736 · 3.53 Impact Factor
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    ABSTRACT: Cancer stem cells are becoming recognised as being responsible for metastasis and treatment resistance.The complex cellular and molecular network that regulates cancer stem cells and the role that inflammation plays in cancer progression are slowly being elucidated. Cytokines, secreted by tumour associated immune cells, activate the necessary pathways required by cancer stem cells to facilitate cancer stem cells progressing through the epithelial-mesenchymal transition and migrating to distant sites. Once in situ, these cancer stem cells can secrete their own attractants, thus providing an environment whereby these cells can continue to propagate the tumour in a secondary niche.
    Cancer letters 08/2014; 345(2):271-278. DOI:10.1016/j.canlet.2013.07.031 · 5.02 Impact Factor
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    ABSTRACT: Pitavastatin is the latest statin to be approved and has shown beneficial effects on plasma lipid profiles. The aim of the present meta-analysis was to assess both the efficacy and safety of pitavastatin versus simvastatin, one of the most commonly used statins.
    Clinical Drug Investigation 07/2014; 34(9). DOI:10.1007/s40261-014-0215-0 · 1.70 Impact Factor
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    ABSTRACT: To investigate the effects of a high-carbohydrate and low-fat (HC/LF) diet on plasma lipids and apolipoproteins (Apos) of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL) rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Apo B-100 and Apo A-I were analyzed at baseline and before and after the HC/LF diet. The results show that, when compared with before the HC/LF diet, only the male G carriers experienced increased HDL-C (p = 0.008) and Apo A-I (p = 0.005) after the HC/LF diet. Decreased TC in both males and females and increased TG in females were found regardless of the genotype after the HC/LF diet. LDL-C decreased in all the subjects although the decrease was not significant in the female G carriers. These results demonstrate that the G allele of LPL rs326 associates with the elevated levels of HDL-C and Apo A-I after the HC/LF diet in males of the healthy Chinese Han Youth.
    International Journal of Environmental Research and Public Health 04/2014; 11(4):4544-54. DOI:10.3390/ijerph110404544 · 1.99 Impact Factor
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    ABSTRACT: Different diets consumed by individuals of different ethnicities, gender, and age may cause changes in blood pressure. The current study sought to investigate changes in blood pressures after consumption of a high-carbohydrate (high-CHO) diet by healthy Chinese adolescents. As a population, the Chinese consume a diet with a high carbohydrate content and they have a low incidence of hypertension and coronary artery disease. Dietary data were collected using a 3-day diet diary. Subjects were 672 high school students who were divided into a high-CHO diet group (≥ 55% carbohydrates) and a non-high-CHO diet group (< 55% carbohydrates, < 40% fats). Plasma glucose levels, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Body mass index (BMI), waist-to-hip ratio (WHR), pulse pressure (PP), and mean arterial pressure (MAP) were calculated. Results indicated that males had a higher BMI, glucose level, SBP, DBP, PP, and MAP than females. When diet was taken into account, males in the non-high-CHO diet group had a higher SBP and PP than females. Males in the high-CHO diet group had a higher glucose level than females. Males in the high-CHO diet group had a lower SBP (p = 0.004) and PP (p = 0.002) than males in the non-high-CHO diet group and females in the high-CHO diet group had a lower glucose level (p = 0.003) than females in the non-high-CHO diet group. After adjusting for age, BMI, WHR, heart rate, the total daily energy intake, and the intake of vitamin C, calcium, sodium, potassium and magnesium, significant differences in SBP and PP were noted in males. These results indicate that male adolescents consuming a high-CHO diet had a lower SBP and PP than males consuming a non-high-CHO diet.
    Bioscience trends 01/2014; 8(2):132-7. DOI:10.5582/bst.8.132 · 1.21 Impact Factor
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    ABSTRACT: Changes in the ratios of plasma lipids and apolipoproteins may be associated with diets and the C161T polymorphism in the gene of peroxisome proliferators activated receptor gamma (PPARgamma). As a result, this study was to investigate the effects of this polymorphism on changes of the ratios induced by a high-carbohydrate (high-CHO) diet. After a washout diet of 54% carbohydrate for 7 days, 56 healthy young adults (22.89 +/- 1.80 years old) were given the high-CHO diet of 70% carbohydrate for 6 days. Height, weight, waist circumference (WC), glucose, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) AI, and apoB100 at baseline and before and after the high-CHO diet were measured. Body mass index (BMI), TG/HDL-C, log (TG/HDL-C), TC/HDL-C, LDL-C/HDL-C, and apoB100/apoAI were calculated. PPARgamma C161T was detected by a PCR-RFLP method. The relationship between the polymorphism and the ratios were analyzed. The female T carriers had higher BMI and WC than the female CC homozygotes at baseline and before and after the diet, higher glucose, TG/HDL-C and log (TG/HDL-C) before the diet. In males, when compared to the T carriers, the CC homozygotes had higher TG/HDL-C, log (TG/HDL-C) and apoB100/apoAI at baseline and before and after the diet, higher glucose at baseline, higher LDL-C/HDL-C and TC/HDL-C before and after the diet. Compared with those before the high-CHO diet, TC/HDL-C and LDL-C/HDL-C decreased after the diet regardless of gender and the genotypes. Decreased BMI and WC were observed in the male CC homozygotes but only decreased BMI in the female T carriers. Notably, decreased apoB100/apoAI was observed in the male T carriers, while elevated TG/HDL-C and log (TG/HDL-C) in the female CC homozygotes, and reduced glucose in the female T carriers. The results suggest that the interplay of gender, the PPARgamma C161T polymorphism and the high-CHO diet can change not only the ratios of plasma lipids and apolipoproteins but also the association of the ratios with plasma glucose, WC, and BMI in healthy Chinese young adults. Once confirmed by larger sample size and multi-center trials, the findings will provide a new scientific basis for personalized dietary intervention for the subjects with different PPARgamma C161T genotypes to reduce risks of CAD, especially in a country with a quarter of the world's population.
    Clinical laboratory 01/2014; 60(4):553-61. DOI:10.7754/Clin.Lab.2013.121031 · 1.08 Impact Factor
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    ABSTRACT: To improve the efficacy of drug delivery, active targeted nanotechnology-based drug delivery systems are gaining considerable attention as they have the potential to reduce side effects, minimize toxicity, and improve efficacy of anticancer treatment. In this work CUR-NPs (curcumin-loaded lipid-polymer-lecithin hybrid nanoparticles) were synthesized and functionalized with ribonucleic acid (RNA) Aptamers (Apts) against epithelial cell adhesion molecule (EpCAM) for targeted delivery to colorectal adenocarcinoma cells. These CUR-encapsulated bioconjugates (Apt-CUR-NPs) were characterized for particle size, zeta potential, drug encapsulation, stability, and release. The in vitro specific cell binding, cellular uptake, and cytotoxicity of Apt-CUR-NPs were also studied. The Apt-CUR-NP bioconjugates exhibited increased binding to HT29 colon cancer cells and enhancement in cellular uptake when compared to CUR-NPs functionalized with a control Apt (P<0.01). Furthermore, a substantial improvement in cytotoxicity was achieved toward HT29 cells with Apt-CUR-NP bioconjugates. The encapsulation of CUR in Apt-CUR-NPs resulted in the increased bioavailability of delivered CUR over a period of 24 hours compared to that of free CUR in vivo. These results show that the EpCAM Apt-functionalized CUR-NPs enhance the targeting and drug delivery of CUR to colorectal cancer cells. Further development of CUR-encapsulated, nanosized carriers will lead to improved targeted delivery of novel chemotherapeutic agents to colorectal cancer cells.
    International Journal of Nanomedicine 01/2014; 9:1083-96. DOI:10.2147/IJN.S59779 · 4.20 Impact Factor
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    ABSTRACT: Background Diets are the important players in regulating plasma lipid profiles. And the R219K polymorphism at the gene of ATP-binding cassette transporter 1(ABCA1) was reported to be associated with the profiles. However, no efforts have been made to investigate the changes of lipid profiles after a high-carbohydrate and low-fat diet in different subjects with different genotypes of this polymorphism. This study was to evaluate the effects of ABCA1 R219K polymorphism on serum lipid and apolipoprotein (apo) ratios induced by a high-carbohydrate/low-fat (high-CHO) diet. After a washout diet of 54.1% carbohydrate for 7 days, 56 healthy young subjects (22.89 ± 1.80 years old) were given a high-CHO diet of 70.1% carbohydrate for 6 days. Height, weight, waist circumference, hip circumference, glucose (Glu), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apoA-1 and apoB-100 were measured on the 1st, 8th and 14th days of this study. Body mass index (BMI), waist-to-hip ratios (WHR), log(TG/HDL-C), TC/HDL-C, LDL-C/HDL-C and apoA-1/apoB-100 were calculated. ABCA1 R219K was analyzed by a PCR-RFLP method. Results The results indicate that the male subjects of all the genotypes had higher WHR than their female counterparts on the 1st, 8th and 14th days of this study. The male K carriers had higher log(TG/HDL-C) and TC/HDL-C than the female carriers on the 1st and 14th days, and higher LDL-C/HDL-C on the 14th day. When compared with that on the 8th day, TC/HDL-C was decreased regardless of the genotypes and genders on the 14th day. Log(TG/HDL-C) was increased in the males with the RR genotype and the female K carriers. Lowered BMI, Glu and LDL-C/HDL-C were found in the male K carriers, but only lowered BMI in the female K carriers and only lowered LDL-C/HDL-C in the females with the RR genotype. Conclusions These results suggest that ABCA1 R219K polymorphism is associated differently in males and females with elevated log(TG/HDL-C) and decreased LDL-C/HDL-C induced by the high-CHO diet.
    Biological research 12/2013; 47(1):1-6. DOI:10.1186/0717-6287-47-4 · 1.04 Impact Factor
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    ABSTRACT: EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70-90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues. Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non-specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.
    PLoS ONE 02/2013; 8(2):e57613. DOI:10.1371/journal.pone.0057613 · 3.53 Impact Factor
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    ABSTRACT: Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX), a sulfatide-containing liposome (SCL) encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX) using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.
    PLoS ONE 11/2012; 7(11):e49277. DOI:10.1371/journal.pone.0049277 · 3.53 Impact Factor
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    ABSTRACT: Cancer stem cells (CSCs) have the capacity to generate the heterogeneous lineages of all cancer cells comprising a tumor and these populations of cells are likely to be more relevant in determining prognosis. However, these cells do not operate in isolation, but instead rely upon signals co-opted from their microenvironment, making the targeting and imaging of CSCs within a cancer mass a daunting task. A better understanding of the molecular cell biology underlying CSC pathology will facilitate the development of new therapeutic targets and novel strategies for the successful eradication of cancer. In addition, the continued investigation of sensitive molecular-imaging modalities will enable more accurate staging, treatment planning and the ability to monitor the effectiveness of CSC-targeted therapies in vivo. In this review, we explore the possibilities and limitations of CSC-directed therapies and molecular imaging modalities.
    Therapeutic delivery 02/2012; 3(2):227-44. DOI:10.4155/tde.11.148
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    ABSTRACT: A high-carbohydrate low-fat (HC/LF) diet and lipoprotein lipase gene (LPL) Ser447Stop and Hind III polymorphisms have separately been found to be associated with triacylglycerol (TG) and high density lipoprotein cholesterol (HDL-C). This study sought to test the effects of LPL polymorphisms and an HC/LF diet on the serum lipid profile of Chinese with a lower incidence of coronary artery disease (CAD) consuming a diet with less fat and more carbohydrates. Fifty-six healthy subjects (22.89 ± 1.80 years) were given a control diet of 30.1% fat and 54.1% carbohydrates for 7 days, followed by an HC/LF diet of 13.8% fat and 70.1% carbohydrate for 6 days; there were no changes in the fatty acid composition or restrictions on total energy. Serum lipid profiles at baseline, before and after the HC/LF diet, and LPL polymorphisms were analyzed. After 6 days of the HC/LF diet, TG and the homeostasis model assessment of insulin resistance (HOMAIR) index were found to increase only in females with S447S. No decrease in HDL-C was noted. In subjects with Hind III polymorphism, increased TG was found in all females but not in males. Increased HDL-C, together with apolipoprotein (apo) AI, was found in male H- carriers but not in males with H+/H+ and females. In conclusion, LPL Ser447Stop and Hind III polymorphisms modified the effects of an HC/LF diet on the serum lipid profiles of a young Chinese population in different ways. Effective strategies for dietary interventions targeted at younger populations should take into account the interplay between genetic polymorphisms, diet, and gender.
    Bioscience trends 10/2011; 5(5):198-204. DOI:10.5582/bst.2011.v5.5.198 · 1.21 Impact Factor
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    ABSTRACT: The lack of a specific targeting strategy against cancer stem cells in current cancer treatment regimens is at least partly responsible for life-threatening cytotoxicity for patients undergoing traditional chemotherapy. An effective cancer stem cell targeting system is urgently required for the next generation of cancer medicine. Epithelial cell adhesion molecule (EpCAM) is overexpressed in most solid cancers and it has recently been identified as a cancer stem cell marker. In this study, we isolated a 40-base RNA aptamer that binds to EpCAM from a random oligonucleotide library using systematic evolution of ligands by exponential enrichment. The aptamer was further truncated to 19 bases. This 19-nt RNA aptamer interacts specifically with a number of live human cancer cells derived from breast, colorectal, and gastric cancers that express EpCAM, but not with those not expressing EpCAM, as analyzed using flow cytometry and confocal microscopy. The binding affinity of the EpCAM RNA aptamer to human cancer cells is approximately 55 nM. Importantly, this EpCAM RNA aptamer is efficiently internalized after binding to cell surface EpCAM. To our knowledge, this is the first RNA aptamer against a cancer stem cell surface marker being developed. Such cancer stem cell aptamers will greatly facilitate the development of novel targeted nanomedicine and molecular imaging agents for cancer theranostics.
    Cancer Science 02/2011; 102(5):991-8. DOI:10.1111/j.1349-7006.2011.01897.x · 3.53 Impact Factor
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    ABSTRACT: Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort.
    Annals of Nutrition and Metabolism 01/2011; 58(2):150-7. DOI:10.1159/000327913 · 2.75 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the interactions of genetic variants in the genes of cholesterol ester transfer protein (CETP) and low-density lipoprotein receptor (LDLR) with high carbohydrate and low fat (HC/LF) diet on lipid profiles in a young and healthy Chinese Han population. Fifty-six healthy subjects (22.89±1.80 years) were given washout diets of 31% fat and 54% carbohydrate for 7 days, followed by HC/LF diets of 15% fat and 70% carbohydrate for 6 days, with no total energy restriction. Serum lipid profiles at baseline, after washout and following HC/LF diets, as well as CETP and LDLR polymorphisms were analyzed. Carriers of B2 allele of CETP TaqIB polymorphism had significantly higher levels of high density lipoprotein cholesterol (HDL-C) and apo A-I in the whole study population after the diet intervention. Notably, males with CETP TaqIB B1B1 experienced significantly increased HDL-C and apo A-I after HC/LF diet. Regarding the LDLR Pvu II polymorphism, both P1P1 subjects and P2 carriers experienced decreased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after HC/LF diet with no statistically significant differences between the genotypes. Our results demonstrate that the elevated HDL-C levels after HC/LF diet in healthy Chinese Han youth are associated with CETP TaqI B2 allele while males with B1B1 genotype are more susceptible to the influence of HC/LF diet on their HDL-C levels. The decreased TC and LDL-C levels after HC/LF diet are not associated with LDLR Pvu II polymorphism.
    The Journal of nutritional biochemistry 02/2010; 21(11):1114-9. DOI:10.1016/j.jnutbio.2009.09.009 · 4.59 Impact Factor

Publication Stats

94 Citations
46.76 Total Impact Points

Institutions

  • 2011–2014
    • Deakin University
      • School of Medicine
      Geelong, Victoria, Australia
  • 2010–2014
    • Sichuan University
      • • Department of Biochemistry and Molecular Biology
      • • Center for Medical Imaging
      Hua-yang, Sichuan, China