Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Folate-decorated nanogels for targeted therapy of ovarian cancer.

ABSTRACT: Nanogels are comprised of swollen polymer networks and nearly 95% water and can entrap diverse chemical and biological agents for cancer therapy with very high loading capacities. Here we use diblock copolymer poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) to form nanogels with the desired degree of cross-linking. The nanogels are further conjugated to folic acid (FA) and loaded with different types of drugs (cisplatin, doxorubicin). For the first time we demonstrate a tumor-specific delivery and superior anti-tumor effect in vivo of an anti-cancer drug using these polyelectrolyte nanogels decorated with folate-targeting groups. This reinforces the use of nanogels for the therapy of ovarian and other cancers, where folate receptor (FR) is overexpressed.

SUBMITTER: Nukolova NV

PROVIDER: S-EPMC3255291 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Folate-decorated nanogels for targeted therapy of ovarian cancer.

Nukolova Natalia V NV Oberoi Hardeep S HS Cohen Samuel M SM Kabanov Alexander V AV Bronich Tatiana K TK

Biomaterials 20110504 23

Nanogels are comprised of swollen polymer networks and nearly 95% water and can entrap diverse chemical and biological agents for cancer therapy with very high loading capacities. Here we use diblock copolymer poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) to form nanogels with the desired degree of cross-linking. The nanogels are further conjugated to folic acid (FA) and loaded with different types of drugs (cisplatin, doxorubicin). For the first time we demonstrate a tumor-specific ...[more]

PMID: 21536326

Similar Datasets

Functionalized Folate-Modified Graphene Oxide/PEI siRNA Nanocomplexes for Targeted Ovarian Cancer Gene Therapy.

Project description:Gene therapy is emerging as a valid method for the treatment of ovarian cancer, including small interfering RNA (siRNA). Although it is so powerful, few targeting efficient gene delivery systems seriously hindered the development of gene therapy. In this study, we synthesized a novel gene vector PEG-GO-PEI-FA by functionalized graphene oxide (GO), in which folic acid (FA) can specifically bind to the folate receptor (FR), which is overexpressed in ovarian cancer. Characterizations of the nanocomplexes were evaluated by dynamic light scattering (DLS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The siRNA condensation ability and stability were assessed by agarose gel electrophoresis. Cellular uptake efficiency and lysosomal escape ability in ovarian cancer cells were investigated by confocal laser scanning microscopy. Furthermore, cellular biosafety of the system and inhibitory of the siRNA tolerability were evaluated by CCK-8 assay. The size of the PEG-GO-PEI-FA nanocomplexes was 216.1 ± 2.457 nm, exhibiting mild cytotoxicity in ovarian cancer cells. With high uptake efficiency, PEG-GO-PEI-FA can escape from the lysosome rapidly and release the gene. Moreover, PEG-GO-PEI-FA/siRNA can effectively inhibit the growth of ovarian cancer cells. By and large, the PEG-GO-PEI-FA/siRNA may offer a promising strategy for siRNA delivery in the treatment of FR-positive ovarian carcinoma or similar tumors.

| S-EPMC7058751 | biostudies-literature

LHRH-targeted nanogels as a delivery system for cisplatin to ovarian cancer.

Project description:Targeted drug delivery using multifunctional polymeric nanocarriers is a modern approach for cancer therapy. Our purpose was to prepare targeted nanogels for selective delivery of chemotherapeutic agent cisplatin to luteinizing hormone-releasing hormone (LHRH) receptor overexpressing tumor in vivo. Building blocks of such delivery systems consisted of innovative soft block copolymer nanogels with ionic cores serving as a reservoir for cisplatin (loading 35%) and a synthetic analogue of LHRH conjugated to the nanogels via poly(ethylene glycol) spacer. Covalent attachment of (D-Lys6)-LHRH to nanogels was shown to be possible without loss in either the ligand binding affinity or the nanogel drug incorporation ability. LHRH-nanogel accumulation was specific to the LHRH-receptor positive A2780 ovarian cancer cells and not toward LHRH-receptor negative SKOV-3 cells. The LHRH-nanogel cisplatin formulation was more effective and less toxic than equimolar doses of free cisplatin or untargeted nanogels in the treatment of receptor-positive ovarian cancer xenografts in mice. Collectively, the study indicates that LHRH mediated nanogel-cisplatin delivery is a promising formulation strategy for therapy of tumors that express the LHRH receptor.

| S-EPMC3809768 | biostudies-literature

Ovarian cancer: opportunity for targeted therapy.

Project description:Ovarian cancer is a common cause of cancer mortality in women with limited treatment effectiveness in advanced stages. The limitation to treatment is largely the result of high rates of cancer recurrence despite chemotherapy and eventual resistance to existing chemotherapeutic agents. The objective of this paper is to review current concepts of ovarian carcinogenesis. We will review existing hypotheses of tumor origin from ovarian epithelial cells, Fallopian tube, and endometrium. We will also review the molecular pathogenesis of ovarian cancer which results in two specific pathways of carcinogenesis: (1) type I low-grade tumor and (2) type II high-grade tumor. Improved understanding of the molecular basis of ovarian carcinogenesis has opened new opportunities for targeted therapy. This paper will also review these potential therapeutic targets and will explore new agents that are currently being investigated.

| S-EPMC3253450 | biostudies-other

Targeted therapy in ovarian cancer.

Project description:Among female-specific cancers worldwide, ovarian cancer is the leading cause of death from gynecologic malignancy in the western world. Despite radical surgery and initial high response rates to first-line chemotherapy, up to 70% of patients experience relapses with a median progression-free survival of 12-18 months. There remains an urgent need for novel targeted therapies to improve clinical outcomes in ovarian cancer. This review aims to assess current understanding of targeted therapy in ovarian cancer and evaluate the evidence for targeting growth-dependent mechanisms involved in its pathogenesis. Of the many targeted therapies currently under evaluation, the most promising strategies developed thus far are antiangiogenic agents and PARP inhibitors.

| S-EPMC5384518 | biostudies-literature

Targeted therapy in ovarian cancer.

Project description:Ovarian cancer is the most common cause of mortality of tumors from gynecologic origin and is often diagnosed after patients have already progressed to advanced disease stage. The current standard of care for treatment of ovarian cancer includes cytoreductive surgery followed by adjuvant chemotherapy. Unfortunately, many patients will recur and ultimately die from their disease. Targeted therapies have been evaluated in ovarian cancer as a method to overcome resistant disease. Angiogenesis inhibitors have shown success in many tumor types and have also demonstrated promise in trials involving patients with ovarian cancer. PARP inhibitors may be potentially active agents in patients with BRCA-associated ovarian cancer. Trials that have evaluated combinations of targeted agents have often revealed untoward toxicities, thus tempering enthusiasm for this approach.

| S-EPMC2814233 | biostudies-literature

Targeted drug delivery via folate receptors in recurrent ovarian cancer: a review.

Project description:Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate-chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate-chemotherapy conjugates.

| S-EPMC4096491 | biostudies-literature

Targeted immune therapy of ovarian cancer.

Project description:Clinical outcomes, such as recurrence-free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathological network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies.

| S-EPMC4369418 | biostudies-literature

Ovarian Cancer: Biomarkers and Targeted Therapy.

Project description:Ovarian cancer is one of the most common causes of death in women as survival is highly dependent on the stage of the disease. Ovarian cancer is typically diagnosed in the late stage due to the fact that in the early phases is mostly asymptomatic. Genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. Early detection of the disorder is one of the most important steps that facilitate a favorable prognosis and a good response to medical therapy for the patients. In targeted therapies, individual patients are treated by agents targeting the changes in tumor cells that help them grow, divide and spread. Currently, in gynecological malignancies, potential therapeutic targets include tumor-intrinsic signaling pathways, angiogenesis, homologous-recombination deficiency, hormone receptors, and immunologic factors. Ovarian cancer is usually diagnosed in the final stages, partially due to the absence of an effective screening strategy, although, over the times, numerous biomarkers have been studied and used to assess the status, progression, and efficacy of the drug therapy in this type of disorder.

| S-EPMC8235073 | biostudies-literature

Dendrimer-decorated nanogels: Efficient nanocarriers for biodistribution <i>in vivo</i> and chemotherapy of ovarian carcinoma.

Project description:Nanomedicine has revolutionized disease theranostics by the accurate diagnosis and efficient therapy. Here, the PAMAM dendrimer decorated PVCL-GMA nanogels (NGs) were developed for favorable biodistribution in vivo and enhanced antitumor efficacy of ovarian carcinoma. By an ingenious design, the NGs with a unique structure that GMA-rich domains were localized on the surface were synthesized via precipitation polymerization. After G2 dendrimer decoration, the overall charge is changed from neutral to positive, and the NGs-G2 display the whole charge nature of positively charged corona and neutral core. Importantly, the unique architecture and charge conversion of NGs-G2 have a profound impact on the biodistribution and drug delivery in vivo. As a consequence of this alteration, the NGs-G2 as nanocarriers emerge the highly sought biodistribution of reduced liver accumulation, enhanced tumor uptake, and promoted drug release, resulting in the significantly augmented antitumor efficacy with low side effects. Remarkably, this finding is contrary to some reported work that the nanocarriers with positive charge have preferential liver uptake. Moreover, the NGs-G2 also displayed thermal/pH dual-responsive behaviors, excellent biocompatibility, improved cellular uptake, and stimuli-responsive drug release. Encouragingly, this work demonstrates a novel insight into the strategy for optimizing design, improving biodistribution and enhancing theranostic efficacy of nanocarriers.

| S-EPMC7970313 | biostudies-literature

Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy.

Project description:The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy.

| S-EPMC5413407 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data