Development of a multi-target peptide for potentiating chemotherapy by modulating tumor microenvironment

Xu, Song; Wan, Zhuoya; Chen, Tijia; Fu, Yao; Jiang, Kejun; Yi, Xiaoli; Ke, Huan; Dong, Jianxia; Yang, Liuqing; Li, Lin; Sun, Xun; Gong, Tao; Zhang, Zhirong

doi:10.1016/j.biomaterials.2016.09.001

Cited by 78 publications

(49 citation statements)

References 48 publications

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“…The surface conjugation of iRGD to liposomes confers the additional advantage of tumor penetration as shown in Table 1 . For example, Song et al reported that the liposomes loaded with iRGD-conjugated doxorubicin enhance the anti-tumor activity in 4T1 breast cancer cells and the depletion efficiency of tumor-associated macrophages (TAMs) as compared with doxorubicin-loaded liposomes [ 107 ]. In addition, studies using iRGD-modified indocyanine green (ICG) liposomes (iRGD-ICG-LPs) reported an increase in tumor inhibitory effect through photothermal therapy (PTT)/ photodynamic therapy (PDT) effects.…”

Section: Applications Of Irgd In Cancer Therapymentioning

confidence: 99%

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

2020

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The unique structure and physiology of a tumor microenvironment impede intra-tumoral penetration of chemotherapeutic agents. A novel iRGD peptide that exploits the tumor microenvironment can activate integrin-dependent binding to tumor vasculatures and neuropilin-1 (NRP-1)-dependent transport to tumor tissues. Recent studies have focused on its dual-targeting ability to achieve enhanced penetration of chemotherapeutics for the efficient eradication of cancer cells. Both the covalent conjugation and the co-administration of iRGD with chemotherapeutic agents and engineered delivery vehicles have been explored. Interestingly, the iRGD-mediated drug delivery also enhances penetration through the blood–brain barrier (BBB). Recent studies have shown its synergistic effect with BBB disruptive techniques. The efficacy of immunotherapy involving immune checkpoint blockades has also been amplified by using iRGD as a targeting moiety. In this review, we presented the recent advances in iRGD technology, focusing on cancer treatment modalities, including the current clinical trials using iRGD. The iRGD-mediated nano-carrier system could serve as a promising strategy in drug delivery to the deeper tumor regions, and be combined with various therapeutic interventions due to its novel targeting ability.

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Section: Applications Of Irgd In Cancer Therapymentioning

confidence: 99%

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

2020

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“…In vivo, suppressed tumor growth, metastasis, and angiogenesis were observed [178]. Most recently, using an elegant liposomal modification for the simultaneous targeting of TAM, endothelial cells, and tumor cells, the cyclic RGD peptide (iRGD) was combined with a substrate for legumain, alanine-alanine-asparagine (AAN), yielding nRGD [179]. nRGD could specifically bind to legumain, present on tumor endothelial cells, tumor cells, and TAM.…”

Section: Passive and Active Targetingmentioning

confidence: 99%

“…Furthermore, the TME was modulated by depletion of TAM. Overall, the attachment of nRGD to doxorubicin-loaded liposomes led to excellent anti-tumor efficacy, increasing doxorubicin efficacy and low toxicity [179]. …”

Section: Passive and Active Targetingmentioning

confidence: 99%

Nanomedicine Strategies to Target Tumor-Associated Macrophages

Binnemars-Postma

Storm

Prakash

2017

IJMS

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In recent years, the influence of the tumor microenvironment (TME) on cancer progression has been better understood. Macrophages, one of the most important cell types in the TME, exist in different subtypes, each of which has a different function. While classically activated M1 macrophages are involved in inflammatory and malignant processes, activated M2 macrophages are more involved in the wound-healing processes occurring in tumors. Tumor-associated macrophages (TAM) display M2 macrophage characteristics and support tumor growth and metastasis by matrix remodeling, neo-angiogenesis, and suppressing local immunity. Due to their detrimental role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer may prove to be beneficial in the treatment of cancer. Due to the plastic nature of macrophages, their activities may be altered to inhibit tumor growth. In this review, we will discuss the therapeutic options for the modulation and targeting of TAM. Different therapeutic strategies to deplete, inhibit recruitment of, or re-educate TAM will be discussed. Current strategies for the targeting of TAM using nanomedicine are reviewed. Passive targeting using different nanoparticle systems is described. Since TAM display a number of upregulated surface proteins compared to non-TAM, specific targeting using targeting ligands coupled to nanoparticles is discussed in detail.

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“…35 Song et al developed a “tadpole”-like peptide (nRGD) that contained iRGD and a tumor associated macrophage (TAM) targeting sequence (alanine-alanine-asparagine). 35 It was demonstrated that conjugating the nRGD to the liposomal carrier could dramatically improve antitumor efficacy, attributed to the specific interaction with tumor vascular endothelial cells capable of efficient tumor penetration, together with the capacity of the depletion of the TAMs in the breast tumor microenvironment. Interestingly, iRGD peptide can also be used to improve the endogenous nano subject for tumor targeting.…”

Section: Irgd-mediated Tumor Targetingmentioning

confidence: 99%

Targeted drug delivery using iRGD peptide for solid cancer treatment

Liu

Jiang

et al. 2017

Mol. Syst. Des. Eng.

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Many solid tumor types, such as pancreatic cancer, have a generally poor prognosis, in part because the delivery of therapeutic regimen is prohibited by pathological abnormalities that block access to tumor vasculature, leading to poor bioavailability. Recent development of tumor penetrating iRGD peptide that is covalently conjugated on nanocarriers’ surface or co-administered with nanocarriers becomes a popular approach for tumor targeting. More importantly, scientists have unlocked an important tumor transcytosis mechanism by which drug carrying nanoparticles directly access solid tumors (without the need of leaky vasculature), thereby allowing systemically injected nanocarriers more abundantly distribute at tumor site with improved efficacy. In this focused review, we summarized the design and implementation strategy for iRGD-mediated tumor targeting. This includes the working principle of such peptide and discussion on patient-specific iRGD effect in vivo, commensurate with the level of key biomarker (i.e. neuropilin-1) expression on tumor vasculature. This highlights the necessity to contemplate the use of a personalized approach when iRGD technology is used in clinic.

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Development of a multi-target peptide for potentiating chemotherapy by modulating tumor microenvironment

Cited by 78 publications

References 48 publications

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

iRGD Peptide as a Tumor-Penetrating Enhancer for Tumor-Targeted Drug Delivery

Nanomedicine Strategies to Target Tumor-Associated Macrophages

Targeted drug delivery using iRGD peptide for solid cancer treatment

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