Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

Gao, Wei; Ye, Guihua; Duan, Xiao-Chuan; Yang, Xiaoying; Yang, Victor C.

doi:10.2147/ijn.s115215

Cited by 45 publications

(28 citation statements)

References 33 publications

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“…In a study conducted by Gao et al., a biodegradable pH‐sensitive micellar doxorubicin DDV was devised with the surface conjugation of a modified seven peptide transferrin receptor ligand (7pep; amino‐acid sequence: HAIYPRH) . Doxorubicin encapsulating micelles composed of 7pep conjugated 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine and polyethylene glycol‐2000 (DSPE‐PEG 2000 ) were used in nude mice bearing drug‐resistant MCF‐7 xenografts (MCF‐7/Adr) which overexpress Tfr . Micelles were evaluated for internalization and therapeutic effect at formulations of varying 7pep modification (10%, 30%, 50%, 60% 7pep).…”

Section: Receptor Targets For Drug Resistant Tumorsmentioning

confidence: 99%

Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

Large

Soucy

Hebert

et al. 2018

Advanced Therapeutics

141

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Receptor-mediated drug delivery presents an opportunity to enhance therapeutic efficiency by accumulating drug within the tissue of interest and reducing undesired, off-target effects. In cancer, receptor overexpression is a platform for binding and inhibiting pathways that shape biodistribution, toxicity, cell binding and uptake, and therapeutic function. This review will identify tumor-targeted drug delivery vehicles and receptors that show promise for clinical translation based on quantitative in vitro and in vivo data. The authors describe the rationale to engineer a targeted drug delivery vehicle based on the ligand, chemical conjugation method, and type of drug delivery vehicle. Recent advances in multivalent targeting and ligand organization on tumor accumulation are discussed. Revolutionizing receptor-mediated drug delivery may be leveraged in the therapeutic delivery of chemotherapy, gene editing tools, and epigenetic drugs.in the site of interest. This is clinically important as reaching a therapeutic dosage locally and reducing systemic toxicity can be life-threatening or life-saving events for cancer patients.The design of targeted DDVs can be optimized by altering the size, shape, material, ligand, and ligand orientation. For systemic delivery, spherical DDVs less than 200 nm in diameter are standard, which is balanced by the trade off between surface area and volume ratio. DDVs are prepared from biomaterials based on the size, hydrophobicity, and ideal release of the drug. There are a diverse range of ligand candidates for DDV functionalization, including monoclonal antibodies (mAbs), peptides, oligosaccharides, small molecules, and aptamers. [5] These ligands can be tethered to vehicles or conjugated directly to drugs by covalent (typically thiol or amide-based reactions, or "click" chemistry) or noncovalent attachment; the type of reaction is often based on the material of the DDV. [6] Multi-targeted and patterned DDVs improved cancer cell binding and the overall therapeutic benefit in vivo. The ideal DDV platform may be rationally designed by evaluating the drug, release mechanism, mode of delivery into the body, and target cells.Utilizing these approaches, targeted DDVs were successfully translated from the research setting into clinical use, or are currently in preclinical trials. [7] Liposomal based DDVs were approved for use in cancer therapy, treating fungal diseases, analgesics, photodynamic therapy, and viral vaccines. [8] Specifically, FDA approved liposomal drug formulations, such as Mepact, Maribo, and Epaxal were proven to be effective for the treatment of nonmetastatic osteosarcoma, acute lymphoblastic leukemia, and hepatitis A, respectively. [9] Many targeted DDVs in clinical use are utilized for the treatment of multiple cancer types, as there is often broad overlap in malignant receptor overexpression across various carcinogenic tissues (Figure 1). The widely successful drug Pembrolizumab (Keytruda), a humanized IgG4 isotype mAb that targets the programmed cell death (PD-1) rec...

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Section: Receptor Targets For Drug Resistant Tumorsmentioning

confidence: 99%

Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

Large

Soucy

Hebert

et al. 2018

Advanced Therapeutics

141

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“…Gao et al designed a micellar system called 7-pep HD micelles, and the in vitro study on MCF/Adr cells and in vivo study on MDR tumors-loaded female nude mice indicated that these biodegradable micelles can effectively target the MDR tumor whose surface overexpresses transferrin and overcomes MDR. 87 Gastric cancer tends to overexpress MiR-21; to combat this condition, Wu et al developed a novel nano-delivery system called anti-miRNA oligonucleotide-21-human epidermal growth factor receptorpoly(ethylene glycol)-poly(ε-caprolactone) nanoparticles, and then used it to encapsulate trastuzumab to target gastric cancer cells in vitro and in vivo. 88 As a result, gastric cancer cells were more sensitive to drugs, and this demonstrated the enormous potential of antibody-dependent targeted transport.…”

Section: Polymeric Micellesmentioning

confidence: 99%

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Zhang¹,

Tang²,

Liu³

et al. 2017

IJN

132

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Chemotherapy is still one of the main cancer therapy treatments, but the curative effect of chemotherapy is relatively low, as such the development of a new cancer treatment is highly desirable. The gradual maturation of nanotechnology provides an innovative perspective not only for cancer therapy but also for many other applications. There are a diverse variety of nanoparticles available, and choosing the appropriate carriers according to the demand is the key issue. The performance of nanoparticles is affected by many parameters, mainly size, shape, surface charge, and toxicity. Using nanoparticles as the carriers to realize passive targeting and active targeting can improve the efficacy of chemotherapy drugs significantly, reduce the mortality rate of cancer patients, and improve the quality of life of patients. In recent years, there has been extensive research on nanocarriers. In this review, the effects of several major parameters of nanoparticles on their physical and chemical properties are reviewed, and then the recent progress in the application of several commonly used nanoparticles is presented.

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“…The pH at the surface of highly metastatic cells within tumors was found to be even more acidic, about 6.1–6.4 . Some pH‐sensitive micelles have been developed for efficient intracellular delivery in response to endolysosomal pH (pH endo : 6.0‒5.0) . Despite some of the particles being successfully endocytosed by the tumor cells, most of them become trapped in acid endolysosomes and are unable to release the drug .…”

Section: Introductionmentioning

confidence: 99%

Fullerene as a doxorubicin nanotransporter for targeted breast cancer therapy: Capillary electrophoresis analysis

2018

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The clinical use of doxorubicin (DOX) is limited by dose-related cardiomyopathy, which becomes more prevalent with increasing cumulative doses of the drug. Complexes of fullerene with DOX were designed and studied using biophysical methods. The ability of DOX to release from fullerene at different pHs was analyzed. It has been shown that the size of the fullerene-DOX complexes was ∼280 nm. The zeta potential for fullerene was -30 mV, for DOX -8 mV, and for fullerene-DOX conjugates -24 mV. Drug release was studied by CE with LIF detection. When fullerene-DOX conjugates were separated in a pH 7.5 buffer, 43% of all DOX signals were derived from free DOX, with the signal increasing as pH decreased. At pH 5.25, all DOX had been released and 100% of the signal was derived from free DOX. The release of DOX from complexes with fullerene at lower pH can be used in targeted antineoplastic therapy, resulting in lower toxicity for less acidic non-target tissue.

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Transferrin receptor-targeted pH-sensitive micellar system for diminution of drug resistance and targetable delivery in multidrug-resistant breast cancer

Cited by 45 publications

References 33 publications

Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

Effects of major parameters of nanoparticles on their physical and chemical properties and recent application of nanodrug delivery system in targeted chemotherapy

Fullerene as a doxorubicin nanotransporter for targeted breast cancer therapy: Capillary electrophoresis analysis

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