Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment

David, Ayelet

doi:10.1016/j.addr.2017.05.006

Cited by 106 publications

(52 citation statements)

References 243 publications

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“…Peptide ligands demonstrate wide applications, for instance, the cyclic arginine–glycine–aspartic acid (cRGD) peptide can strongly and specifically internalize with both cancer and angiogenic endothelial cells overexpressing integrins (e.g., α v β 1 , α v β 3 , and α v β 5 ) . Besides, proteins can also be used as targeting ligands . One of the most investigated protein for modification of the surface of nanocarriers is transferrin (Tf), a glycoprotein with a molecular weight ≈80 kDa, which has a high affinity to Tf receptors (TfRs) on the cell surface for intracellular transportation of iron .…”

Section: Targeting Moieties On Nanocarriersmentioning

confidence: 99%

“…[27] Besides, proteins can also be used as targeting ligands. [28] One of the most investigated protein for modification of the surface of nanocarriers is transferrin (Tf), a glycoprotein with a molecular weight ≈80 kDa, which has a high affinity to Tf receptors (TfRs) on the cell surface for intracellular transportation of iron. [29] Due to the upregulation of TfRs on cancer cells, as well as on brain capillaries, Tf-installed nanocarriers have been developed for various targeting strategies, such as delivering anticancer compounds into cancer cells or promoting the access of nanocarriers into the brain.…”

Section: Arsenal Of Targeting Moietiesmentioning

confidence: 99%

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Ligand‐Installed Nanocarriers toward Precision Therapy

2019

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Development of drug‐delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand‐installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand‐installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand‐installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.

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Section: Targeting Moieties On Nanocarriersmentioning

confidence: 99%

Section: Arsenal Of Targeting Moietiesmentioning

confidence: 99%

Ligand‐Installed Nanocarriers toward Precision Therapy

2019

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“…29,30 Micelles can penetrate tumor very effectively and this makes them ideal when combined with targeting moieties. 31 However, such an ability also means that they dilute and end up into other organs leading to either side-effect or diluting the PDT effect. We thus propose the design of a nanocomposite hydrogel to prolong micelle residency in the site of injection to focus PDT locally.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Thermosensitive nanocomposite gel for intra-tumoral two-photon photodynamic therapy

Luo

Zhang

Luo

et al. 2019

Journal of Controlled Release

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We propose here a new approach to achieve intratumoral near-infrared (NIR) two-photon photodynamic therapy (PDT). We established a composite micellar thermosensitive hydrogel made of clinically approved methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA) and Pluronic (F127). The mPEG-PDLLA form micelles that can be loaded with two-photon absorption compound (T1) and photosensitizer (PS), The F127 micelles are liquid at room temperature and while forming an hydrogel at body temperature.This enables an in situ gelification upon injection providing long-term retentio within the tumor. The NIR light is thus upconverted into visible light by T1 and excited PS. The morphology, rheology properties and releasing profiles of hydrogel were fully characterized. The rheology properties and releasing mechanism was investigated. The composite hydrogel showed significant cytotoxicity to 4T1 murine breast cancer cells upon NIR laser irradiation, while it showed non-significant cytotoxicity without. Time-dependent in vivo and ex vivo distribution results suggested that hydrogel administrated via intra-tumoral injection could prolong both PDT agents retention in tumor. We show here that the use of NIR radiation allows deep tissue penetration and inhibition of tumor growth of more than 50% even under 1 cm thick muscle tissue.Recently, we reported the design, synthesis, and full optical characterization of a novel imidazole derivative, T1, which exhibit large TPA cross-section (~100 GM) in the NIR region (800-900 nm). 25 We combine here T1 with pyropheophorbide a (PPa), a hydrophobic PS from chlorophyll a derivatives. Pheophorbide compounds are considered a second-generation PS as they have improved properties over porphyrin based ones. 26 mPEG-PDLLA micelles are expected to improve the biodistribution of drug molecules and promote PDT effect by preventing PS molecules from aggregating. 27, 28 mPEG-PDLLA micelles are biodegradable and showed good biocompatibility being based on PEG and PDLLA polymers both being classified as generally ACCEPTED MANUSCRIPT

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“…36 Peptide ligands are highly selective for target tissue/cells, and multiple ligands can be conjugated to a single drug carrier to offer multivalent conjugation, thus increasing binding affinity to the target. 37 CPP details are presented in the following section.…”

Section: • •mentioning

confidence: 99%

“…101,102 In addition to the altered morphology, tumor vasculature differs from that of normal by its molecular composition. 37 Arginine-glycine-aspartic acid (RGD) and NGR peptides are the most extensively studied peptides for targeting tumor vasculature. 101 RGD peptides can selectively target tumor vasculature expressing α γ β 3 and α γ β 5 integrins, and an NGR peptide (CNGRC) binds to CD13 (aminopeptidase N), which is expressed in the tumor vasculature specifically.…”

Section: Peptides-targeting Tumor Vasculaturementioning

confidence: 99%

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

Kebebe¹,

Liu²,

Wu³

et al. 2018

IJN

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Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

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Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment

Cited by 106 publications

References 243 publications

Ligand‐Installed Nanocarriers toward Precision Therapy

Ligand‐Installed Nanocarriers toward Precision Therapy

Thermosensitive nanocomposite gel for intra-tumoral two-photon photodynamic therapy

Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

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