Estrogen-anchored pH-sensitive liposomes as nanomodule designed for site-specific delivery of doxorubicin in breast cancer therapy.

The present investigation reports the development of nanoengineered estrogen receptor (ER) targeted pH-sensitive liposome for the site-specific intracellular delivery of doxorubicin (DOX) for breast cancer therapy. Estrone, a bioligand, was anchored on the surface of pH-sensitive liposome for drug targeting to ERs. The estrone-anchored pH-sensitive liposomes (ES-pH-sensitive-SL) showed fusogenic potential at acidic pH (5.5). In vitro cytotoxicity studies carried out on ER-positive MCF-7 breast carcinoma cells revealed that ES-pH-sensitive-SL formulation was more cytotoxic than non-pH-sensitive targeted liposomes (ES-SL). The flow cytometry analysis confirmed significant enhanced uptake (p < 0.05) of ES-pH-sensitive-SL by MCF-7 cells. Intracellular delivery and nuclear localization of the DOX was confirmed by fluorescence microscopy. The mechanism for higher cytotoxicity shown by estrone-anchored pH-sensitive liposomal-DOX was elucidated using reactive oxygen species (ROS) determination. The in vivo biodistribution studies and antitumor activities of formulations were evaluated on tumor bearing female Balb/c mice followed by intravenous administration. The ES-pH-sensitive-SL efficiently suppressed the breast tumor growth in comparison to both ES-SL and free DOX. Serum enzyme activities such as LDH and CPK levels were assayed for the evaluation of DOX induced cardiotoxicity. The ES-pH-sensitive-SL accelerated the intracellular trafficking of encapsulated DOX, thus increasing the therapeutic efficacy. The findings support that estrone-anchored pH-sensitive liposomes could be one of the promising nanocarriers for the targeted intracellular delivery of anticancer agents to breast cancer with reduced systemic side effects.

• Publication year

  2012

• Venue

  Molecular Pharmaceutics

• Publication date

  Unknown publication date

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1021/mp200439zPMID 22091702
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Liposomal nanomedicine for breast cancer therapy.

  2011cited by this paper
• A novel cancer targeting approach based on estrone anchored stealth liposome for site-specific breast cancer therapy.

  2010cited by this paper
• Targeted delivery of doxorubicin via estrone-appended liposomes

  2008cited by this paper
• Targeted delivery of doxorubicin via estrone-appended liposomes.

  2008cited by this paper
• Estrogen(s) and analogs as a non-immunogenic endogenous ligand in targeted drug/DNA delivery.

  2007cited by this paper
• Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+increase are reciprocally modulated in rat cardiomyocytes

  2006cited by this paper
• Recent advances with liposomes as pharmaceutical carriers

  2005cited by this paper
• Oxidative stress and apoptosis in metal ion-induced carcinogenesis.

  2004cited by this paper
• On the formulation of pH-sensitive liposomes with long circulation times.

  2004cited by this paper
• Steroid hormone receptors in breast cancer management

  2004cited by this paper
• Characterization of Amphotericin B Liposome Formulations

  2004cited by this paper
• Accelerated clearance of PEGylated liposomes in rats after repeated injections.

  2003cited by this paper
• Targeted delivery and triggered release of liposomal doxorubicin enhances cytotoxicity against human B lymphoma cells.

  2001cited by this paper
• Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells.

  2001cited by this paper
• Reactive oxygen species in cell signaling.

  2000cited by this paper
• A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin.

  1999cited by this paper
• Cationic lipids, phosphatidylethanolamine and the intracellular delivery of polymeric, nucleic acid-based drugs (review).

  1998cited by this paper
• Doxorubicin physical state in solution and inside liposomes loaded via a pH gradient.

  1998cited by this paper
• Sterically Stabilized pH-sensitive Liposomes

  1997cited by this paper
• Cytoplasmic delivery of calcein mediated by liposomes modified with a pH-sensitive poly(ethylene glycol) derivative.

  1997cited by this paper
• Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size.

  1995cited by this paper
• Kinetic analysis of endocytosis and intracellular fate of liposomes in single macrophages.

  1995cited by this paper
• Dehydration-induced lamellar-to-hexagonal-II phase transitions in DOPE/DOPC mixtures.

  1993cited by this paper
• Evaluation of 2',7'-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells.

  1993cited by this paper
• pH-sensitive liposomes for delivery of macromolecules into cytoplasm of cultured cells.

  1993cited by this paper
• Sterically stabilized liposomes: improvements in pharmacokinetics and antitumor therapeutic efficacy.

  1991cited by this paper
• Flow Cytometric Analysis of Respiratory Burst Activity in Phagocytes With Hydroethidine and 2′,7′‐Dichlorofluorescin

  1990cited by this paper
• N-succinyldioleoylphosphatidylethanolamine: structural preferences in pure and mixed model membranes.

  1988cited by this paper
• High-performance liquid chromatographic determination of doxorubicin and its metabolites in plasma and tissue.

  1988cited by this paper
• Acid- and calcium-induced structural changes in phosphatidylethanolamine membranes stabilized by cholesteryl hemisuccinate.

  1985cited by this paper
• pH‐sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules

  1985cited by this paper
• pH-induced destabilization of phosphatidylethanolamine-containing liposomes: role of bilayer contact.

  1984cited by this paper
• Rapid separation of low molecular weight solutes from liposomes without dilution.

  1978cited by this paper

• Tailored Liposomal Nanocarriers for Precision Breast Cancer Therapy

  2026cites this paper
• “LINEAGE OF LIPID-BASED ENDOSOMAL ESCAPE IN CYTOSOLIC DELIVERY TO CANCER: INSIGHT INTO AN UNPRECEDENTED APPROACH”

  2025cites this paper
• Co-encapsulated with shikonin/doxorubicin pH-sensitive liposomes: preparation, characterization and its synergistic effect in drug-resistant breast cancer cells.

  2025cites this paper
• Advances in targeted drug delivery systems for cancer treatment: Current trends and future prospects

  2025cites this paper
• Encapsulation of doxorubicin in magnesium acetate liposomes as a pH-sensitive drug carrier for tumor therapy

  2025cites this paper
• Emerging Combinatorial Drug Delivery Strategies for Breast Cancer: A Comprehensive Review.

  2025cites this paper
• Emerging Nanoparticle-Based Diagnostics and Therapeutics for Cancer: Innovations and Challenges

  2025cites this paper
• Reducing toxicity and enhancing efficacy of doxorubicin by liposomal doxorubicin and aprepitant in breast cancer

  2025cites this paper
• Advances in lipid-based carriers for cancer therapeutics: Liposomes, exosomes and hybrid exosomes.

  2023cites this paper
• Functionalized liposomes for targeted breast cancer drug delivery

  2023cites this paper
• Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

  2023cites this paper
• Cancer nanomedicine: Recent developments in drug delivery systems and strategies to overcome eventual barriers to achieve a better outcome

  2023cites this paper
• α-Tocopherol Polyethylene Glycol 1000 Succinate-Based Cationic Liposome for the Intracellular Delivery of Doxorubicin in MDA-MB-231 Triple-Negative Breast Cancer Cell Line

  2023cites this paper
• Multifunctional nanotherapeutics for intracellular trafficking of doxorubicin against breast cancer.

  2023cites this paper
• Antibody-conjugated pH-sensitive liposomes for HER-2 positive breast cancer: development, characterization, in vitro and in vivo assessment

  2023influential citation
• Engineered Liposomes in Interventional Theranostics of Solid Tumors.

  2023cites this paper
• Reduction of Doxorubicin-Induced Cardiotoxicity by Co-Administration of Smart Liposomal Doxorubicin and Free Quercetin: In Vitro and In Vivo Studies

  2023cites this paper
• pH-sensitive liposomes bearing a chemotherapeutic agent and a natural apoptosis modulator for effective intracellular delivery to the solid tumor

  2023cites this paper
• Controlling the Biological Behaviors of Polymer-Coated Upconverting Nanoparticles by Adjusting the Linker Length of Estrone Ligands.

  2022cites this paper
• Challenges and emerging strategies for next generation liposomal based drug delivery: An account of the breast cancer conundrum.

  2022cites this paper
• A decade's worth of impact: Dox loaded liposomes in anticancer activity

  2022cites this paper
• Exploration of Site-Specific Drug Targeting—A Review on EPR-, Stimuli-, Chemical-, and Receptor-Based Approaches as Potential Drug Targeting Methods in Cancer Treatment

  2022cites this paper
• Nanomedicine and versatile therapies for cancer treatment

  2022cites this paper
• Ligand-mediated nanomedicines against breast cancer: a review.

  2022cites this paper
• Triggered Drug Release From Liposomes: Exploiting the Outer and Inner Tumor Environment

  2021cites this paper
• Doxorubicin nanoformulations on therapy against cancer: An overview from the last 10 years.

  2021cites this paper
• pH-Sensitive liposomes with embedded ampholytic derivatives of cholan-24-oic acid

  2021cites this paper
• Recent advances in active targeting of nanomaterials for anticancer drug delivery.

  2021cites this paper
• Targeting steroid hormone receptors for anti-cancer therapy-A review on small molecules and nanotherapeutic approaches.

  2021cites this paper
• Integrin α2β1 Targeting DGEA-Modified Liposomal Doxorubicin Enhances Antitumor Efficacy against Breast Cancer.

  2021cites this paper
• Efficient in vitro and in vivo docetaxel delivery mediated by pH-sensitive LPHNPs for effective breast cancer therapy.

  2021cites this paper
• Development and optimization of TPGS-based stealth liposome of doxorubicin using Box–Behnken design: characterization, hemocompatibility, and cytotoxicity evaluation in breast cancer cells

  2021cites this paper
• Nanomedicine-based multidrug resistance reversal strategies in cancer therapy

  2021cites this paper
• A novel approach to a controlled opening of liposomes.

  2020cites this paper
• Use of Nanoparticles in Medicine

  2020cites this paper
• A cancer-specific activatable theranostic nanodrug for enhanced therapeutic efficacy via amplification of oxidative stress

  2020cites this paper
• Estrone decorated poly-ion complex micelles for targeted melittin delivery to hormone responsive breast cancer cells.

  2020cites this paper
• Designing Aptamer-Gold Nanoparticle-Loaded pH-Sensitive Liposomes Encapsulate Morin for Treating Cancer

  2020cites this paper
• Stimuli-responsive sugar-derived hydrogels: A modern approach in cancer biology

  2020cites this paper
• Fabrication and characterization of tumor nano-lysates as a preventative vaccine for breast cancer.

  2020cites this paper
• Multicompartment Polymeric Nanocarriers for Biomedical Applications.

  2020cites this paper
• Dual cancer targeting using estrogen functionalized chitosan nanoparticles loaded with doxorubicin-estrone conjugate: A quality by design approach.

  2020cites this paper
• Hypoxia-Responsive, Polymeric Nanocarriers for Targeted Drug Delivery to Estrogen Receptor-Positive Breast Cancer Cell Spheroids.

  2020cites this paper
• Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

  2020cites this paper
• Nanotheranostics for Cancer Therapy and Detection: State of the Art.

  2020cites this paper
• Liposomal doxorubicin as targeted delivery platform: Current trends in surface functionalization.

  2020cites this paper
• Enhanced Lycopene Delivery Using Estrogen Receptor Targeted Nanoparticles For Breast Cancer Therapy

  2020cites this paper
• Targeted Nanomedicine in Chemoprevention

  2020cites this paper
• Controlled Delivery of Chemopreventive Agents

  2020cites this paper
• pH Sensitive Lipid-Polymer Hybrid Nanoparticles Mediated Delivery of Docetaxel: A Viable Approach for Breast Cancer Therapeutic Intervention Development

  2020cites this paper
• Recent advances on thermosensitive and pH-sensitive liposomes employed in controlled release.

  2019cites this paper
• Optimized synthesis, characterization and in vitro systematic evaluation of adamantane-doxorubicin prodrugs sensitive to pH in breast cancer cells

  2019cites this paper
• An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites

  2019cites this paper
• Endogenous Stimuli-Responsive Linkers in Nanoliposomal Systems for Cancer Drug Targeting.

  2019cites this paper
• ASSESSMENT OF CANCER TARGETING POTENTIAL OF DOXORUBICIN CONJUGATED WITH SURFACE FUNCTIONALIZED MULTI-WALLED CARBON NANOTUBES

  2019cites this paper
• Molecular dynamics study on the configuration and arrangement of doxorubicin in carbon nanotubes

  2018cites this paper
• Immunoliposomes in clinical oncology: State of the art and future perspectives

  2018cites this paper
• Stimuli-responsive Smart Liposomes in Cancer Targeting.

  2018cites this paper
• Estrogen-functionalized liposomes grafted with glutathione-responsive sheddable chotooligosaccharides for the therapy of osteosarcoma

  2018cites this paper
• Development of doxorubicin hydrochloride loaded pH‐sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH‐sensitivity

  2018cites this paper
• Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

  2018cites this paper
• State of the Art of Stimuli-Responsive Liposomes for Cancer Therapy

  2017cites this paper
• An artemisinin-mediated ROS evolving and dual protease light-up nanocapsule for real-time imaging of lysosomal tumor cell death.

  2017cites this paper
• Editorial: Nanotherapeutics for Cancer Imaging and Therapy.

  2017cites this paper
• Surface modification of lipid-based nanocarriers for cancer cell-specific drug targeting

  2017cites this paper
• Membrane-Loaded Doxorubicin Liposomes Based on Ion-Pairing Technology with High Drug Loading and pH-Responsive Property

  2017cites this paper
• Liposome-targeted delivery for highly potent drugs

  2017cites this paper
• Active Targeting of Breast Cancer Cells Using Nanocarriers

  2017cites this paper
• Recent developments in anticancer drug delivery using cell penetrating and tumor targeting peptides

  2017cites this paper
• Chapter 7 – Targeting and imaging of cancer cells using nanomaterials

  2016cites this paper
• Injectable hydrogel-based drug delivery systems for local cancer therapy.

  2016cites this paper
• Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin

  2016cites this paper
• A review of mechanistic insight and application of pH-sensitive liposomes in drug delivery

  2015cites this paper
• Review on triggered liposomal drug delivery with a focus on ultrasound.

  2015cites this paper
• Novel pH-sensitive drug carriers of carboxymethyl-hexanoyl chitosan (Chitosonic® Acid) modified liposomes

  2015cites this paper
• Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

  2015cites this paper
• One platform comparison of estrone and folic acid anchored surface engineered MWCNTs for doxorubicin delivery.

  2015cites this paper
• Controllable drug uptake and nongenomic response through estrogen-anchored cyclodextrin drug complex

  2015cites this paper
• Liposomal drug release using ultrasound and modeling release dynamics for model predictive controller design

  2015cites this paper
• Preparation of pH-sensitive anionic liposomes designed for drug delivery system (DDS) application.

  2015cites this paper
• Targeting ion transport in cancer

  2014cites this paper
• Utilizing liposomes and lipid nanoparticles to overcome challenges in breast cancer treatment

  2014cites this paper
• Enhanced noscapine delivery using estrogen-receptor-targeted nanoparticles for breast cancer therapy

  2014cites this paper
• Efficacious anticancer drug delivery mediated by a pH-sensitive self-assembly of a conserved tripeptide derived from tyrosine kinase NGF receptor.

  2014cites this paper
• Breast cancer: major risk factors and recent developments in treatment.

  2014cites this paper
• Nanotechnology Approaches to Target Endosomal pH: A Promising Strategy for an Efficient Intracellular Drug, Gene and Protein Delivery

  2014cites this paper
• Polymer-Modified Liposomes: From Long-Circulating to Multifunctional

  2014cites this paper
• Synergistic dual-targeting hydrogel improves targeting and anticancer effect of Taxol in vitro and in vivo.

  2014cites this paper
• Self-assembled inorganic/organic hybrid nanoparticles with multi-functionalized surfaces for active targeting drug delivery.

  2013cites this paper
• Glutaminase isoenzymes as key regulators in metabolic and oxidative stress against cancer.

  2013cites this paper
• Expedition of liposomes to intracellular targets in solid tumors after intravenous administration

  2013cites this paper
• Deposition of Doxorubicin in Rats following Administration of Three Newly Synthesized Doxorubicin Conjugates

  2013cites this paper
• pH-sensitive liposomes for drug delivery in cancer treatment.

  2013cites this paper
• Recent Trends in Multifunctional Liposomal Nanocarriers for Enhanced Tumor Targeting

  2013cites this paper
• Targeting Drugs to Cancer: A Tough Journey to the Tumor Cell

  2013cites this paper
• Enhancing Cell Nucleus Accumulation and DNA Cleavage Activity of Anti-Cancer Drug via Graphene Quantum Dots

  2013cites this paper
• Targeted breast cancer nanotherapeutics: options and opportunities with estrogen receptors.

  2012cites this paper
• Investigation of the Role of Encapsulated miR-372 in Chitosan on Induction of Apoptosis in MCF-7 Cancer Cells

  year unknowncites this paper