Synergistic dual-targeting hydrogel improves targeting and anticancer effect of Taxol in vitro and in vivo

Shu, Chang; Li, Ruixin; Yin, Yajun; Yin, Deyan; Gu, Yueqing; Ding, Li; Zhong, Wenying

doi:10.1039/c4cc05614k

Cited by 33 publications

(17 citation statements)

References 30 publications

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“…A hydrogel‐based delivery system functionalized with estrone and RGD peptide ligands (Et‐peptide‐Taxol hydrogel) was devised for paclitaxel delivery to breast carcinoma via EGFR and α v β 3 integrin receptor‐mediated endocytosis . At concentrations of 50 and 100 n m , Et‐peptide‐Taxol hydrogel DDVs developed by Shu et al.…”

Section: Ddv Optimizationmentioning

confidence: 99%

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Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

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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: Ddv Optimizationmentioning

confidence: 99%

“…In vivo, the Et‐peptide‐Taxol hydrogel was found to selectively accumulate in tumor tissue and bladder in MCF7 tumor bearing mice. Full renal clearance was achieved by 48 h, at which time Et‐peptide‐Taxol hydrogel particles were still highly retained within tumor tissue …”

Section: Ddv Optimizationmentioning

confidence: 99%

Advances in Receptor‐Mediated, Tumor‐Targeted Drug Delivery

Large

Soucy

Hebert

et al. 2018

Advanced Therapeutics

141

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“…Zhong and coworkers designed a synergistic dual-targeting hydrogel that was able to transport drugs for specifically targeting tumors. [295] Experimental results revealed the accumulation of hydrogel within the cancer cells in vitro as well as in breast tumor in vivo . They confirmed that the estrone and RGD peptide acted as the tumor-targeting moieties and contributed to the selective accumulation of the hydrogel in the breast tumor.…”

Section: Applications Of Supramolecular Biofunctional Materialsmentioning

confidence: 99%

“…As discussed in the previous section, supramolecular hydrogels have already shown promises as possible cancer drug delivery systems. [277, 295, 297–300] In this section we discuss the recent development in the use of supramolecular hydrogelators themselves as innovative anticancer therapeutics.…”

Section: Applications Of Supramolecular Biofunctional Materialsmentioning

confidence: 99%

Supramolecular biofunctional materials

et al. 2017

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This review discusses supramolecular biofunctional materials, a novel class of biomaterials formed by small molecules that are held together via noncovalent interactions. The complexity of biology and relevant biomedical problems not only inspire, but also demand effective molecular design for functional materials. Supramolecular biofunctional materials offer (almost) unlimited possibilities and opportunities to address challenging biomedical problems. Rational molecular design of supramolecular biofunctional materials exploit powerful and versatile noncovalent interactions, which offer many advantages, such as responsiveness, reversibility, tunability, biomimicry, modularity, predictability, and, most importantly, adaptiveness. In this review, besides elaborating on the merits of supramolecular biofunctional materials (mainly in the form of hydrogels and/or nanoscale assemblies) resulting from noncovalent interactions, we also discuss the advantages of small peptides as a prevalent molecular platform to generate a wide range of supramolecular biofunctional materials for the applications in drug delivery, tissue engineering, immunology, cancer therapy, fluorescent imaging, and stem cell regulation. This review aims to provide a brief synopsis of recent achievements at the intersection of supramolecular chemistry and biomedical science in hope of contributing to the multidisciplinary research on supramolecular biofunctional materials for a wide range of applications. We envision that supramolecular biofunctional materials will contribute to the development of new therapies that will ultimately lead to a paradigm shift for developing next generation biomaterials for medicine.

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“…Compared with intravenous injection of clinically used Taxol® with four times the dosage, this hydrogel could inhibit tumor growth more efficiently by a single dose of intratumor administration, which suggested the big potential of this novel gelation system of Taxol for cancer therapy. In one of our previous articles, a novel synergistic dual‐targeting molecular self‐assembly hydrogel of Taxol was developed by conjugation with estrone and RGD peptide, which transported drugs, specifically targeted tumors, and penetrated breast cancer cells. Confocal imaging in vitro and real‐time visualization in vivo were carried out to evidence enhanced targeted delivery and anticancer effect of Taxol.…”

Section: Introductionmentioning

confidence: 99%