MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

Yan, Wei; Song, Sha; Duan, Nianxiu; Wang, Feng; Wang, Yuxi; Yang, Yiwei; Peng, Chengyuan; Li, Junjun; Nie, Di; Zhang, Xinxin; Guo, Shiyan; Zhu, Chunliu; Yu, Miaorong; Gan, Yong

doi:10.1002/advs.201902746

Cited by 39 publications

(29 citation statements)

References 37 publications

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“…5 ). This approach prevented excessive endothelial cell endocytosis and ensured sufficient interaction of cilengitide with α v β 3 integrins on endothelial cells to form new blood vessels into ischemic areas, thereby improving the delivery of drug-loaded liposomes [ 79 ]. Compared with the previously mentioned ECM depletion strategy [ 37 , 38 , 46 ], which cannot be strictly controlled, this treatment promoted angiogenesis and blood perfusion, but it did not increase the risk of tumor metastasis [ 80 , 81 ], suggesting that this strategy can safely address the challenge of pancreatic hypoperfusion for drug delivery.…”

Section: Angiogenesismentioning

confidence: 99%

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Jia

Zhang

et al. 2021

J Nanobiotechnol

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Pancreatic cancer is one of the most lethal malignant tumors with a low survival rate, partly because the tumor microenvironment (TME), which consists of extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), immune cells, and vascular systems, prevents effective drug delivery and chemoradiotherapy. Thus, modulating the microenvironment of pancreatic cancer is considered a promising therapeutic approach. Since nanoparticles are one of the most effective cancer treatment strategies, several nano-delivery platforms have been developed to regulate the TME and enhance treatment. Here, we summarize the latest advances in nano-delivery systems that alter the TME in pancreatic cancer by depleting ECM, inhibiting CAFs, reversing immunosuppression, promoting angiogenesis, or improving the hypoxic environment. We also discuss promising new targets for such systems. This review is expected to improve our understanding of how to modulate the pancreatic cancer microenvironment and guide the development of new therapies. Graphical Abstract

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Section: Angiogenesismentioning

confidence: 99%

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Jia

Zhang

et al. 2021

J Nanobiotechnol

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“…Improvement of tumor blood perfusion is one of the strategies to resolve tumor-associated hypoperfusion hindering nanoparticle penetration. Wei et al 134 developed doxorubicin-loaded liposomes that carried low-density cilengitide, an αvβ3 integrin-specific cyclic peptide, via a membrane type 1-matrix metalloproteinase (MT1-MMP) cleavable peptide. In vivo, cilengitide, at a low dose showed the proangiogenic activity through cleavage by MT1-MMP on tumor endothelial cells and increased tumor blood perfusion, thereby improving the tumor accumulation and distribution of doxorubicin-loaded liposomes.…”

Section: Targeting the Vasculature System In Pancreatic Cancermentioning

confidence: 99%

Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer

Lü¹,

Prakash²

2021

IJN

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Pancreatic cancer is one of the most malignant tumors with one of the worst survival rates due to its insidious onset and resistance to therapies. Most therapeutics show a desired anticancer effect in vitro; however, very poor efficacy in vivo because of the limited drug delivery and penetration into pancreatic tumors attributed to the abundance of the tumor stroma, ie, the fibrotic tumor microenvironment surrounding the cancer cells. For a better understanding of the challenges posed by the pancreatic tumor stroma, we outline the key features of the tumor microenvironment. Then we highlight major strategies used to tackle the challenges to improve drug penetration into the tumor and achieve enhanced efficacy (pre)clinically. Furthermore, we describe nanomedicine strategies to modulate the tumor stroma, degrade the extracellular matrix, and co-deliver multi-functional drugs, to improve the chemotherapeutics delivery and penetration into pancreatic tumors.

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“…Ex vivo assays demonstrated a pro-angiogenic effect of MC-T-DOX. In vivo mice bearing BxPC pancreatic tumors show reduced tumor growth [58].…”

Section: Vascular Promotion Therapymentioning

confidence: 99%

The Dual Effect of the BMP9–ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?

Ayuso-Íñigo

Méndez-García

Pericacho

et al. 2021

Cancers

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The improvement of cancer therapy efficacy, the extension of patient survival and the reduction of adverse side effects are major challenges in cancer research. Targeting blood vessels has been considered a promising strategy in cancer therapy. Since the tumor vasculature is disorganized, leaky and triggers immunosuppression and tumor hypoxia, several strategies have been studied to modify tumor vasculature for cancer therapy improvement. Anti-angiogenesis was first described as a mechanism to prevent the formation of new blood vessels and prevent the oxygen supply to tumor cells, showing numerous limitations. Vascular normalization using low doses of anti-angiogenic drugs was purposed to overcome the limitations of anti-angiogenic therapies. Other strategies such as vascular promotion or the induction of high endothelial venules are being studied now to improve cancer therapy. Bone morphogenetic protein 9 (BMP9) exerts a dual effect through the activin receptor-like kinase 1 (ALK1) receptor in blood vessel maturation or activation phase of angiogenesis. Thus, it is an interesting pathway to target in combination with chemotherapies or immunotherapies. This review manuscript explores the effect of the BMP9–ALK1 pathway in tumor angiogenesis and the possible usefulness of targeting this pathway in anti-angiogenesis, vascular normalization or vascular promotion therapies.

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MT1‐MMP‐Activated Liposomes to Improve Tumor Blood Perfusion and Drug Delivery for Enhanced Pancreatic Cancer Therapy

Cited by 39 publications

References 37 publications

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Nanoparticle-based delivery systems modulate the tumor microenvironment in pancreatic cancer for enhanced therapy

Nanomedicine Strategies to Enhance Tumor Drug Penetration in Pancreatic Cancer

The Dual Effect of the BMP9–ALK1 Pathway in Blood Vessels: An Opportunity for Cancer Therapy Improvement?

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