Pdf delivery of calf thymus dna to tumor by folate. Folate receptor fr is a cellular marker selectively overexpressed in a significant fraction of. These bimodal liposomes were composed of both a paramagnetic and a fluorescent lipid, and utilized a peglipid amphiphile for prolonged in vivo circulation. New folate receptor targeted nano liposomes for delivery of 5fluorouracil to cancer cells. Liposomes were modified with folatederivatized peg. Pdf folate receptor targeted bimodal liposomes for tumor.
To overcome these barriers, we developed a folate receptor targeted codelivery system folate doxorubicinbmi1 sirna. This formulation was designed to overcome vehicle toxicity associated with the traditional cremophor elbased formulation and to provide the added advantages of prolonged systemic circulation time and selective targeting of the fr, which is frequently overexpressed on. To compare the in vivo tissue distribution of folate targeted liposomes ftls injected i. This trojan horse process, which was created by drs. On the basis of the epr effect, liposomes further modified by tumoractivetargeted ligands such as antibodies, peptides, and small compounds like folate have been widely investigated. But ee had tendency to be slightly decreased as time went by. Folate receptor targeted imaging using pegfolate 407 weeks after kb cell implantation and at a total of 5 weeks after initiation of the folatefree diet. Tumor cell targeting is a promising drug delivery strategy.
International journal of nanomedicine 20111111 folate receptor targeted fluorescent paramagnetic bimodal liposomes for tumor imaging. Microfluidic synthesis of pegylated and folate receptortargeted liposomes for drug delivery renee r. Preparation and evaluation of pegylated and folatepegylated. Plp and fplp were produced using a film hydration method as previously described 17, 19, 38. B clinical effects of liposomes encapsulating methotrexate on arthritis. Strong implication for enhanced potency and safety author links open overlay panel somayeh handali a eskandar moghimipour a b maryam kouchak a zahra ramezani a mohsen amini c kambiz ahmadi angali d sadegh saremy b farid abedin dorkoosh e f mohsen rezaei g. Preparation, characterization and pharmacokinetics of folate receptortargeted liposomes for docetaxel delivery guangxi zhai, 1, 2, jun wu, 1, guangya xiang, 1, 3 wenxue mao, 4 bo yu, 5, 6 hong li, 1 longzhu piao, 1 l. Aug 25, 2010 mycn amplification is highly associated with malignancy and correlates with poor prognosis in patients with neuroblastoma. Codelivery of doxorubicin and bmi1 sirna by folate receptor targeted liposomes exhibits enhanced antitumor effects in vitro and in vivo tan yang1, 1bin li 1, 1shibo qi, yong liu, yongkang gai1, peng ye1, guang yang, wendian zhang1, peng zhang2, xingxing he3, weijie li4, zhiping zhang1, guangya xiang1, chuanrui xu1 1. Doctor of philosophy in the discipline of biochemistry, school of life sciences. We considered that this result was due to the release of ptx which was attached to the surface of the liposomes. Folate receptortargeted liposomes loaded with a diacid. The folate receptor fr has two glycosyl phosphatidylinositol gpianchored isoforms. Folate targeted bimodal paramagnetic and fluorescent liposomes were developed and showed enhanced accumulation in a folate receptor expressing tumor model.
This study examined the effect of polyethylene glycol peg spacer length and folate ligand density on the targeting ability of folate modified liposomes. Folate receptortargeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for h22 hepatocellular carcinoma both in vitro and in vivo minchen liu, 1 lin liu, 1 xiarong wang, 1 wuping shuai, 2 ying hu, 3 min han, 1 and jianqing gao 1. Folate, as a targeting ligand, offers unique advantages over immunoliposomes, i. Folate targeting is a method utilized in biotechnology for drug delivery purposes. Folate receptor targeting liposomes reduce intratumoral accumulation. However, sirnabased treatments targeting bmi1 gene have been restricted to limited delivery, low bioavailability and hence relatively reduced efficacy. Devoe1 1university of maryland, college park, usa, 2university of maryland, baltimore, usa, 3national institute of standards and technology, usa. This increase in liposome uptake could be blocked by 1 mm free folate. Folate receptor targeting of radiolabeled liposomes reduces. The median serum folate level in humans has shown an increase since the fda recommended dietary folate supplementation in the late 1990s from 12. A folate receptortargeted liposomal formulation for. In addition, direct cytotoxicity of ctdna has been found in tissue culture and in mice. New folate receptor targeted nano liposomes for delivery of 5.
Farred fluorescent liposomes for folate receptortargeted. A folate receptortargeted liposomal formulation for paclitaxel. Improved therapeutic activity of folatetargeted liposomal. Folate receptor targeted gene delivery using cationic. Efficient intracellular drug and gene delivery using. Folate receptor targeted imaging using poly ethylene glycol. The liposomes were specifically targeted to breast cancer cells overexpressed folate receptor. Devoe1 1university of maryland, college park, usa, 2university of maryland, baltimore, usa, 3national institute of. Folate receptortargeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for h22 hepatocellular carcinoma both in vitro and in vivo minchen liu,1 lin liu,1 xiarong wang,1 wuping shuai,2 ying hu,3 min han,1 jianqing gao1 1institute of pharmaceutics, college of pharmaceutical sciences, 2first affiliated hospital, college of medicine, zhejiang university. Folate receptortargeted liposomes enhanced the antitumor. Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging. Mycn amplification is highly associated with malignancy and correlates with poor prognosis in patients with neuroblastoma. Formulation strategies for folatetargeted liposomes and.
Targeting liposomes to the fr has been proposed as a way to enhance the effects of liposomebased chemotherapy. Each liposome preparation was assessed at concentrations ranging between 6 and 100 nmolml of phospholipid and the cellassociated. Folate receptortargeted quantum dot liposomes as fluorescence probes liposomes as fluorescence probes article pdf available in journal of drug targeting 177. A novel liposomal formulation of paclitaxel targeting the folate receptor fr was synthesized and characterized. Low, involves the attachment of the vitamin, folate folic acid, to a moleculedrug to form a folate conjugate.
The first description of direct folate cytotoxic drug conjugates was by ladino et al. To overcome these barriers, we developed a folate receptor targeted codelivery system folatedoxorubicinbmi1 sirna. Folate receptor targeted bimodal liposomes for tumor. This result also implies that the circulating folate in serum is not high enough to cause significant inhibition of the binding of folatecoated liposomes to the target cells.
Preparation, characterization and pharmacokinetics of folate. Moreover, a549 cells folate receptor deficient cells have not shown variations in the liposomal incorporation. Request pdf folate receptortargeted liposomes as vectors for therapeutic agents the folate receptor is a cell surface protein that has recently been identified as a tumor marker, due to its. Apr 01, 2011 as a result, the photocytotoxicity induced by folate targeted liposomes was improved. These bimodal liposomes were composed of both a paramagnetic and a fluorescent lipid, and utilized a peg. Targeting the folate receptor for the treatment of ovarian cancer. Folate receptor targeted liposomes encapsulating anticancer drugs volume.
The development of new treatment options is needed and efforts have focused on targeted therapies which aim to improve patient outcome by increasing antitumor activity while minimizing toxicity. Folate receptor targeted liposomes encapsulating anticancer. Intracellular uptake and intracavitary targeting of folate. In this paper, we describe the newly designed liposomes modified with amphiphilic farred squaraine dye and folic acid for its application in folate receptortargeted bioimaging. Receptortargeted delivery of liposomes via folate pegchol article in journal of liposome research 1023. Microfluidic synthesis of peg and folateconjugated. Effectsofpolyethyleneglycolspacerlengthandliganddensity. Cholesterol as a bilayer anchor for pegylation and targeting. Liposomes incorporating a lipophilic folate derivative, such as folate pegdspe or folate pegchol, have been shown to efficiently deliver antitumor agents into frbearing tumor cells via receptor mediated endocytosis. Folate receptor targeted liposomes bentham science. Therefore, combining phsensitive formulations with fr targeting could potentially improve drug or gene delivery to. Codelivery of doxorubicin and bmi1 sirna by folate receptor targeted liposomes exhibits enhanced antitumor effects in vitro and in vivo. Pdf the folate receptor fr is a tumorassociated antigen that can bind with folic acid fa and its conjugates with high affinity and ingests. Anticancer drugs, drug encapsulation, folate receptor targeting, liposomes, ovarian cancer.
Strong implication for enhanced potency and safety. Preparation, characterization and pharmacokinetics of. Tumour celltargeted liposomal delivery has the potential to enhance the therapeutic efficacy and reduce the toxicity of anticancer agents. Uptake of folatetargeted radiolabeled liposomes into j6456fr lymphoma cells. Based on the natural high affinity of folate for the folate receptor protein fr, which is commonly expressed on the. Imaging of the radiolabeled conjugate after sedating the mice with ketamine mixed with xylazine, 99mtc peg folate was administered intravenously via a tail vein to the animals. Request pdf folate receptor targeted liposomes encapsulating anticancer drugs among all available lipid based nanoparticulate systems, the success of liposomal drug delivery system is evident. Folatetargeted liposomes have been well considered in folate receptor fr overexpressing cells including mcf7 and 4t1 cells in vitro and in vivo. Imatinib inhibits plateletderived growth factor receptor pdgfr, and. The zeta potential values of the blank liposomes figure figure1a, 1a, both plp and fplp, were higher than that of the pdnaliposome complexes fplppil15, fplppc3. A folate receptortargeted lipoplex delivering interleukin.
Based on the natural high affinity of folate for the. Gadoliniumdtpa liposomes as a potential mri contrast agent. Multimodality imaging offers unique advantages over traditional single modality imaging. Folate receptor targeted gene delivery using cationic liposomes as nonviral vectors s. Cholesterol as a bilayer anchor for pegylation and. Targeted delivery via selective cellular markers can potentially increase the efficacy and reduce the toxicity of therapeutic agents. This study attempted to prepare polyethyleneglycol modified pegylated and folatepegylated liposomes containing paclitaxel ptx in order to reduce the toxicity and improve the bioavailability and biocompatibility by targeting drugs to the lymphatics using cancer cell specific ligand folate to prevent metastasis via the lymphatic system. In vivo fate of folatetargeted polyethyleneglycol liposomes. Moreover, a549 cells folate receptor deficient cells have. Bmi1 gene overexpression is found in various human tumors and has been shown as a potential target for gene treatment. Strategy for the treatment of acute myelogenous leukemia. In this study, we prepared and characterized different targeted.
This study examined the effect of polyethylene glycol peg spacer length and folate ligand density on the targeting ability of folatemodified liposomes. The folate receptor is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery of anticancer agents to folate receptorexpressing tumors. The objective of this study is to design an optimum folate targeted liposomal formulations which show the best liposome cell uptake to tumor cells. This selectivity was completely inhibited with an excess of folic acid present in the cell culture media.
Imaging of the radiolabeled conjugate after sedating the mice with ketamine mixed with xylazine, 99mtc pegfolate. Low, involves the attachment of the vitamin, folate, to a moleculedrug to form a folate conjugate. Full text folate receptortargeted liposomes enhanced the. Liposomes were prepared using hspc, cholesterol, and fapegsa. Nan ding, yao lu, robert j lee, chang yang, lei huang, jian liu, guangya xiang. Incorporation of folate constructs onto the surface of drugloaded liposomes was shown to dramatically improve the potency and specificity of the liposomes against frpositive tumor cells 28,29. Prospects in folate receptortargeted radionuclide therapy. New folate receptor targeted nano liposomes for delivery. Oc1 folatetargeted liposomes for rheumatoid arthritis. Preparation and characterization of liposomes and lipoplexes. Pdf folate receptortargeted liposomes loaded with a.
Folate receptor targeted liposomes encapsulating anti. Folate receptor targeted imaging using peg folate 407 weeks after kb cell implantation and at a total of 5 weeks after initiation of the folate free diet. Liposomes were modified with folate derivatized peg. In vivo specific targeting and prophylactic efficiency of folate receptortargeted liposomes in arthritic mice. As shown in table 2, the particle size and ee of both pegylated and folatepegylated liposomes in ph 7. These studies suggest that cholesterol is a viable bilayer anchor for synthesis of pegylated and. While conventional therapies have improved the outcome for patients with ovarian cancer, the disease still accounts for the most gynecological cancerrelated deaths. Tumourselective drug delivery via folate receptortargeted liposomes. The folate receptor fr is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery of anticancer agents to frexpressing tumors. We developed a novel liposomemycn sirnafolic acid complex, and the transfection efficacy was measured in lan5 cells by cy3 fluorescence density in each microgram of protein from the transfected cell lysate. The average particle size of liposomes used in this study was approximately nm, and the folate modi. Effects of polyethylene glycol spacer length and ligand.
Preparation and evaluation of pegylated and folate. Pdf delivery of calf thymus dna to tumor by folate receptor. Folate receptor targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for h22 hepatocellular carcinoma both in vitro and in vivo minchen liu,1 lin liu,1 xiarong wang,1 wuping shuai,2 ying hu,3 min han,1 jianqing gao1 1institute of pharmaceutics, college of pharmaceutical sciences, 2first affiliated hospital, college of medicine, zhejiang university. Folate receptortargeted fluorescent paramagnetic bimodal liposomes for tumor imaging nan ding1,2, yao lu1, robert j lee3, chang yang1, lei huang1, jian liu1, guangya xiang1,41school of pharmacy, tongji medical college, huazhong university of science and technology, wuhan, peoples republic of china. This study attempted to prepare polyethyleneglycol modified pegylated and folate pegylated liposomes containing paclitaxel ptx in order to reduce the toxicity and improve the bioavailability and biocompatibility by targeting drugs to the lymphatics using cancer cell specific ligand folate to prevent metastasis via the lymphatic system. Tan yang 1, bin li 1, shibo qi 1, yong liu 1, yongkang gai 1, peng ye 1, guang yang 1, wendian zhang 1, peng zhang 2, xingxing he 3, weijie li 4, zhiping zhang 1, guangya xiang 1, chuanrui xu 1. Efficient intracellular drug and gene delivery using folate. Novel folate receptortargeted lipsomes encapsulated with small size gold nanorods and doxorubicin were developed. Folate receptortargeted liposomes as vectors for therapeutic. More than 80% of folate ligand was inserted in liposomes at each ratio, which was. Long school of pharmacy, 751 brookside road, university of the pacific, stockton, ca, usa for correspondence bjasti. On page 2425, right column, line 7, the sentence however, cholesterol. Jul 15, 2002 this result also implies that the circulating folate in serum is not high enough to cause significant inhibition of the binding of folatecoated liposomes to the target cells. A in vivo uptake specificity of fluorescently labeled liposomes 30 min.
Triggered drug release was obtained with nir laser irradiation. To compare the in vivo tissue distribution of folatetargeted liposomes ftls injected i. Fluorescence microscopy demonstrated differing intracellular fluorescence distributions for targeted phsensitive and nonphsensitive liposomes. Targeting liposomes to the fr has been proposed as a way to enhance the effects of. Folate receptortargeted liposomes enhanced the antitumor potency of imatinib through the combination of active targeting and molecular. Receptorbased tumorselective delivery of therapeutic agents. Folate receptortargeted fluorescent paramagnetic bimodal.
Tumor marker folate receptor frtargeted fluorescent paramagnetic bimodal liposomes were synthesized to codeliver paramagnetic and fluorescence agents for magnetic resonance mr and optical bimodal imaging contrast enhancement. Folate targeted liposomes have been well considered in folate receptor fr overexpressing cells including mcf7 and 4t1 cells in vitro and in vivo. Receptortargeted delivery of liposomes via folatepeg. In addition to evaluating the microfluidic technology as a suitable method for online formation of functionalized liposomes, this work presents several ancillary advancements over previous.
Folate receptor targeted bimodal liposomes for tumor magnetic. The folate receptor fr is a tumorassociated antigen that can bind with folic acid fa and its conjugates with high affinity and ingests. Folatetargeted bimodal paramagnetic and fluorescent liposomes were developed and showed enhanced accumulation in a folate receptor expressing tumor model. Antitumor activity of folate receptortargeted liposomal. In this paper, we describe the newly designed liposomes modified with amphiphilic farred squaraine dye and folic acid for its application in folate receptor targeted bioimaging. Calf thymus dna ctdna has been shown to stimulate macrophages to produce cytokines both in vitro and in vivo when complexed with cationic liposomes. A novel micellar drug delivery approach shiladitya bhattacharya, xiaoling li, janakiram nyshadham and bhaskara jasti department of pharmaceutics and medicinal chemistry, thomas j.
The fr is overexpressed on several cancer cell types including breast, ovarian, endometrial, brain, and bladder cancer. Silencing of the mycn gene by sirna delivered by folate. Pdf formulation strategies for folatetargeted liposomes and. A small fraction of a folatepolyethyleneglycol pegdistearoyl. The folate receptor is an attractive target for selective tumor delivery of liposomal doxorubicin dxr because it is abundantly expressed in a large percentage of tumors. A small fraction of a folate polyethyleneglycol pegdistearoyl. Pdf folate receptortargeted quantum dot liposomes as. Folate receptor targeted imaging using poly ethylene. Targeting the folate receptor for the treatment of ovarian. Pdf folate receptortargeted liposomes loaded with a diacid. Codelivery of doxorubicin and bmi1 sirna by folate. Codelivery of doxorubicin and bmi1 sirna by folate receptor. Discipline of biochemistry, school of life sciences, westville campus, university of kwazulu natal, durban 4000, south africa.
Pdf codelivery of doxorubicin and bmi1 sirna by folate. Folate receptor targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for h22 hepatocellular carcinoma both in vitro and in vivo minchen liu, 1 lin liu, 1 xiarong wang, 1 wuping shuai, 2 ying hu, 3 min han, 1 and jianqing gao 1. This article is from international journal of nanomedicine, volume 9. Folatereceptortargeted delivery of doxorubicin nanoaggregates stabilized by doxorubicinpegfolate conjugate. Submitted in fulfillment of the academic requirements for the degree of.