Tumor acidic microenvironment-induced drug release of RGD peptide nanoparticles for cellular uptake and cancer therapy

Gong, Zhongying; Li, Xiaoying; Zhou, Baolong; Wang, Guohui; Guan, Xiuwen; Xu, Ying; Zhang, Juanjuan; Hong, Zexin; Cao, Juanjuan; Sun, Xirui; Gao, Zhiqin; Lu, Haozheng; Pan, Xingliang; Bai, Jingkun

doi:10.1016/j.colsurfb.2021.111673

Cited by 39 publications

(18 citation statements)

References 55 publications

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“…S7). Compared with normal tissues, an acidic tumor microenvironment spontaneously facilitated cellular uptake and intratumoral penetration, which also accounted for the phenomenon that cRGD-Exo/TP was highly distributed in tumor sites and was low in normal tissues [ 59 , 60 ].…”

Section: Resultsmentioning

confidence: 99%

αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma

Jiang

et al. 2022

J Nanobiotechnol

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Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. Results We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. Conclusion The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma

Jiang

et al. 2022

J Nanobiotechnol

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“…Alternatively, Gao et al developed a double membrane vesicle (DMV), presenting not only the RGD peptide, but also lipopolysaccharides (LPS) (Gao et al, 2021). The association of LPS (normally exposed in the outer membrane of growth for lung and hepatocellular carcinoma in in vivo models (Fu et al, 2021;Gong et al, 2021). Liposomes targeting other integrins are slowly emerging, although selective expression of these integrins in tumor tissue is less evident.…”

Section: Liposomal (Like) Drug Carriersmentioning

confidence: 99%

“…Low treatment efficacy with this approach is caused by ineffective reach of the tumor. The introduction of RGD peptides on the surface of liposomal like vesicles has generally enhanced both drug accumulation in the tumor and anti-tumor efficacy of the drug in mouse models ( Fu et al, 2021 ; Gao et al, 2021 ; Gong et al, 2021 ; Khabazian et al, 2021 ). Additional adjustments were made to the vesicles to further improve their drug transporting characteristics ( Figure 2 ).…”

Section: Integrin Mediated Drug Deliverymentioning

confidence: 99%

“…The association of LPS (normally exposed in the outer membrane of Gram-negative bacteria) with immune cells facilitated the transit of the vesicles from the vasculature into the tumor microenvironment where it could target melanoma cells and deliver therapeutics. Other αvβ3 targeting liposomal like formulations have shown a promising reduction in tumor growth for lung and hepatocellular carcinoma in in vivo models ( Fu et al, 2021 ; Gong et al, 2021 ). Liposomes targeting other integrins are slowly emerging, although selective expression of these integrins in tumor tissue is less evident.…”

Section: Integrin Mediated Drug Deliverymentioning

confidence: 99%

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Targeting Integrins for Cancer Therapy - Disappointments and Opportunities

Bergonzini

Kroese

Zweemer

et al. 2022

Front. Cell Dev. Biol.

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Integrins mediate adhesive interactions between cells and their environment, including neighboring cells and extracellular matrix (ECM). These heterodimeric transmembrane receptors bind extracellular ligands with their globular head domains and connect to the cytoskeleton through multi-protein interactions at their cytoplasmic tails. Integrin containing cell–matrix adhesions are dynamic force-responsive protein complexes that allow bidirectional mechanical coupling of cells with their environment. This allows cells to sense and modulate tissue mechanics and regulates intracellular signaling impacting on cell faith, survival, proliferation, and differentiation programs. Dysregulation of these functions has been extensively reported in cancer and associated with tumor growth, invasion, angiogenesis, metastasis, and therapy resistance. This central role in multiple hallmarks of cancer and their localization on the cell surface makes integrins attractive targets for cancer therapy. However, despite a wealth of highly encouraging preclinical data, targeting integrin adhesion complexes in clinical trials has thus far failed to meet expectations. Contributing factors to therapeutic failure are 1) variable integrin expression, 2) redundancy in integrin function, 3) distinct roles of integrins at various disease stages, and 4) sequestering of therapeutics by integrin-containing tumor-derived extracellular vesicles. Despite disappointing clinical results, new promising approaches are being investigated that highlight the potential of integrins as targets or prognostic biomarkers. Improvement of therapeutic delivery at the tumor site via integrin binding ligands is emerging as another successful approach that may enhance both efficacy and safety of conventional therapeutics. In this review we provide an overview of recent encouraging preclinical findings, we discuss the apparent disagreement between preclinical and clinical results, and we consider new opportunities to exploit the potential of integrin adhesion complexes as targets for cancer therapy.

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“…106,107 However, Lobeek et al identified that OSCC with highly keratinizing phenotype also showed αvβ3 expression on cancer cells using 68 Ga-RGD PET/CT imaging, while αvβ3 expressed at low levels in metastatic lesions as compared with primary OSCC tissues. 108 Researchers usually modified multi-functional nanoplatforms with RGD containing peptides to actively target αvβ3 for OSCC therapeutics, [109][110][111] indicating its potential role in targeted therapy.…”

Section: Integrin αVβ3mentioning

confidence: 99%

Personalized Targeted Therapeutic Strategies against Oral Squamous Cell Carcinoma. An Evidence-Based Review of Literature

Cao¹,

Shi²,

Wang³

et al. 2022

IJN

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Oral squamous cell carcinoma (OSCC) is the most common type of malignant tumor in the head and neck, with a poor prognosis mainly due to recurrence and metastasis. Classical treatment modalities for OSCC like surgery and radiotherapy have difficulties in dealing with metastatic tumors, and together with chemotherapy, they have major problems related to non-specific cell death. Molecular targeted therapies offer solutions to these problems through not only potentially maximizing the anticancer efficacy but also minimizing the treatment-related toxicity. Among them, the receptor-mediated targeted delivery of anticancer therapeutics remains the most promising one. As OSCC exhibits a heterogeneous nature, selecting the appropriate receptors for targeting is the prerequisite. Hence, we reviewed the OSCC-associated receptors previously used in targeted therapy, focused on their biochemical characteristics and expression patterns, and discussed the application potential in personalized targeted therapy of OSCC. We hope that a better comprehension of this subject will help to provide the fundamental information for OSCC personalized therapeutic planning.

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Tumor acidic microenvironment-induced drug release of RGD peptide nanoparticles for cellular uptake and cancer therapy

Cited by 39 publications

References 55 publications

αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma

αvβ3 integrin-specific exosomes engineered with cyclopeptide for targeted delivery of triptolide against malignant melanoma

Targeting Integrins for Cancer Therapy - Disappointments and Opportunities

Personalized Targeted Therapeutic Strategies against Oral Squamous Cell Carcinoma. An Evidence-Based Review of Literature

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