Targeted drug delivery using iRGD peptide for solid cancer treatment

Liu, Xiangsheng; Jiang, Jinhong; Ji, Ying; Lu, Jianqin; Chan, Ryan; Meng, Huan

doi:10.1039/c7me00050b

Cited by 48 publications

(40 citation statements)

References 71 publications

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“…Various iRGD conjugated NPs and iRGD‐drug conjugates have been reported to bind αv integrin‐overexpressing cells with high affinity . The present combined results delineated the mechanism by which iRGD‐DMTPLN sequentially overcome each barrier to deliver drugs to brain metastasis.…”

Section: Resultsmentioning

confidence: 62%

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood–Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor‐Associated Macrophages

Zhang

Lip

et al. 2019

Adv Healthcare Materials

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Owing to the low expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), endocrine and anti-HER2 therapies are ineffective against TNBC. Thus currently, standard adjuvant and neoadjuvant treatments of TNBC are limited to conventional anthracycline-taxanebased chemotherapy. [1] Despite the initial response to chemotherapy, TNBC patients have a high risk of relapse and distal metastases, especially to the brain, leading to shortened survival times. [2] A number of targeted therapies have been investigated to treat TNBC including poly(ADPribose) polymerase (PARP) inhibitors, immune checkpoint inhibitors, antiandrogen agents, phosphoinositide 3-kinase inhibitors, mitogen-activated protein kinase inhibitors, antiangiogenic antibody, and integrin inhibitors. [1,3] Upregulation of cell surface αvβ3 and αvβ5 integrins in aggressive TNBC, especially in brain metastases and tumorassociated vasculature, has presented an opportunity for targeted therapy of TNBC using integrin-targeted peptides. [4] Of various peptide-based inhibitors of αv integrins, Cilengitide, an Arg-Gly-Asp (RGD) peptide mimetic, with high selectivity against integrins αvβ3 and αvβ5, reached phase 3 clinical trial; however, the results were negative. [5] This disappointing outcome may be caused by insufficient amounts of inhibitor reaching tumor cells to generate a direct cytotoxic effect against αvβ3 and αvβ5 positive cancer cells due to the short half-life of Cilengitide in vivo. [5] Nonetheless, RGD-conjugated nanoparticulate drug delivery systems have shown an ability to target chemotherapeutic drugs to integrin-overexpressing tumor vasculature and cancer cells. [6] Despite the promising results in preclinical models, it is challenging to find an optimal RGD particle coverage to balance tumor accumulation against liver uptake. For example, our previous studies on cyclic RGDfK (Arg-Gly-Asp-D-Phe-Lys; cRGD) peptide-conjugated solid-lipid nanoparticles (SLN) or polymer-lipid hybrid nanoparticles (PLN) revealed that a high density of cRGD on the surface led to increased liver uptake Patients with brain metastases of triple negative breast cancer (TNBC) have a poor prognosis owing to the lack of targeted therapies, the aggressive nature of TNBC, and the presence of the blood-brain barrier (BBB) that blocks penetration of most drugs. Additionally, infiltration of tumor-associated macrophages (TAMs) promotes tumor progression. Here, a terpolymer-lipid hybrid nanoparticle (TPLN) system is designed with multiple targeting moieties to first undergo synchronized BBB crossing and then actively target TNBC cells and TAMs in microlesions of brain metastases. In vitro and in vivo studies demonstrate that covalently bound polysorbate 80 in the terpolymer enables the low-density lipoprotein receptor-mediated BBB crossing and TAM-targetability of the TPLN. Conjugation of cyclic internalizing peptide (iRGD) enhances cellular uptake, cytotoxicity, and drug delivery to brain metastases of integrinoverexpressing TNB...

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Section: Resultsmentioning

confidence: 62%

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood–Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor‐Associated Macrophages

Zhang

Lip

et al. 2019

Adv Healthcare Materials

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“…Active targeting, via the agency of a pendant molecular species that has some affinity for the tumor, showed a minor improvement over EPR‐mediated particle accumulation. However, in other (non‐tumor) animal disease models, the use of selective homing agents can generate more substantial accumulation of siRNA . For applications beyond local administration and passive MPS‐mediated homing to clearance organs (e.g., liver, lungs, spleen), the literature contains a wide variety of homing moieties that can be decorated on the surface of carrier particles for in vivo targeting, including aptamers and receptor‐specific ligands .…”

Section: Selective Tissue Targetingmentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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“…These alternative approximations have successfully been evaluated using in vivo tumor models, demonstrating the suitability of using MSNs for tumor drug delivery. In this sense, tumor-homing peptides (e.g., iRGD, iNGR) not only induce spontaneous accumulation of nanoparticles in the tumor tissues, but also enhance their diffusion into the tumoral mass [114,115]. In addition, there are certain types of cells with migratory properties that can transport nanoparticles directly to tumors tissues.…”

Section: Nanotechnology For Cancer Treatmentmentioning

confidence: 99%

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

2020

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Bone diseases, such as bone cancer, bone infection and osteoporosis, constitute a major issue for modern societies as a consequence of their progressive ageing. Even though these pathologies can be currently treated in the clinic, some of those treatments present drawbacks that may lead to severe complications. For instance, chemotherapy lacks great tumor tissue selectivity, affecting healthy and diseased tissues. In addition, the inappropriate use of antimicrobials is leading to the appearance of drug-resistant bacteria and persistent biofilms, rendering current antibiotics useless. Furthermore, current antiosteoporotic treatments present many side effects as a consequence of their poor bioavailability and the need to use higher doses. In view of the existing evidence, the encapsulation and selective delivery to the diseased tissues of the different therapeutic compounds seem highly convenient. In this sense, silica-based mesoporous nanoparticles offer great loading capacity within their pores, the possibility of modifying the surface to target the particles to the malignant areas and great biocompatibility. This manuscript is intended to be a comprehensive review of the available literature on complex bone diseases treated with silica-based mesoporous nanoparticles—the further development of which and eventual translation into the clinic could bring significant benefits for our future society.

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Targeted drug delivery using iRGD peptide for solid cancer treatment

Cited by 48 publications

References 71 publications

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood–Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor‐Associated Macrophages

Multitargeted Nanoparticles Deliver Synergistic Drugs across the Blood–Brain Barrier to Brain Metastases of Triple Negative Breast Cancer Cells and Tumor‐Associated Macrophages

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

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