Improving drug delivery to solid tumors: Priming the tumor microenvironment

Khawar, Iftikhar Ali; Kim, Jung Ho; Kuh, Hyo-Jeong

doi:10.1016/j.jconrel.2014.12.018

Cited by 426 publications

(331 citation statements)

References 126 publications

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“…[37] On contrary, to enhance the vascular permeability, vascular normalization strategies aim to transforming the aberrant tumor vasculatures into closely resembling normal vasculatures in order to enhance the structural and functional integrity of the vasculature networks by increasing the pericytes coverage, reducing the IFP and leakiness of the vessels (Figure 5A). [155] Thus, by normalizing the tumor vasculature, the solid tumor stress may be reduced and promote the nanoparticle penetration efficiency. Proangiogenic proteins like vascular endothelial growth factors (VEGF) are over-expressed in many tumors that are primarily driving the angiogenesis process.…”

Section: Modulating the Tumor Microenvironment For Cancer Therapymentioning

confidence: 99%

“…[156] Therefore, VEGF can be a therapeutic target for the vascular normalization approach. [155] Normalizing the tumor vasculature using anti-VEGFR-2 antibodies in mouse tumor, blocked the VEGFR-2 receptors and decreased the pore size of tumor vessel wall, which in turn allowed the enhanced delivery of small nanoparticles (12 nm) and at same time hindered the delivery of 60 and 125 nm sized nanoparticles. [157] However, the normalized vessels presenting the size restrictions for this strategy and allowed only smaller nanoparticles (< 60 nm) to be rapidly transported to the tumor tissue.…”

Section: Modulating the Tumor Microenvironment For Cancer Therapymentioning

confidence: 99%

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Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Section: Modulating the Tumor Microenvironment For Cancer Therapymentioning

confidence: 99%

Section: Modulating the Tumor Microenvironment For Cancer Therapymentioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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show abstract

“…A range of extracellular proteases are produced which are known to degrade the extracellular matrix allowing for invasion and tumour progression. Together, these factors hinder drug distribution and reduce the therapeutic efficacy of nanoparticles as delivery to the target site is impeded [36].…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

2016

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The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective non-viral delivery systems can be applied successfully in oncology.Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration.

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“…It involves the administration of a PS agent either intravenously or topologically to the body which can accumulate in cancer tissue largely due to the enhanced permeability and retention (EPR) effect [9][10][11] . These PS agents can be activated with specific wavelengths to produce reactive oxygen species (ROS), often singlet oxygen, which in turn induces irreversible cancer tissue damage.…”

Section: Porphyrins and Pdtmentioning

confidence: 99%

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

Moylan¹,

Scanlan²,

Senge

2015

CMC

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Abstract:This review presents an in-depth overview of the modification of porphyrins with bioconjugates and their applications in medicine today. Porphyrin bioconjugates ranging from nucleotides to steroids are under active scrutiny. However, carbohydrates have been at the forefront of such research in recent years and offer significant potential. This is attributed to their own selectivity to lectins on the surface of cancer cells and their influence on the amphiphilicity of the porphyrin macrocycle. These characteristics and the tendency of porphyrin photosensitizers to accumulate in tumor tissues make glycoporphyrins promising candidates for use as photosensitizers. Thus, a detailed overview of the synthesis and biological evaluation of glycoporphyrins is given with a particular focus on their applications in photodynamic therapy and their future prospects as drug candidates have been reported.

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Improving drug delivery to solid tumors: Priming the tumor microenvironment

Cited by 426 publications

References 126 publications

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Delivery of Nucleic Acids for Cancer Gene therapy: Overcoming extra- and intra-cellular Barriers

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

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