Extracellular matrix remodeling in vivo for enhancing tumor-targeting efficiency of nanoparticle drug carriers using the pulsed high intensity focused ultrasound

Lee, Sang‐Min; Han, Hyounkoo; Koo, Heebeom; Na, Jin Hee; Yoon, Hong Yeol; Lee, Jun Young; Lee, Hyukjin; Kim, Hyuncheol; Kwon, Ick Chan; Kim, Kwangmeyung

doi:10.1016/j.jconrel.2017.02.035

Cited by 112 publications

(89 citation statements)

References 30 publications

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“…Due to the presence of several components within the TM, tumor cells are exposed to chemotherapeutic drugs in a gradient fashion. The ECM by forming thick fibers within the tumor present a physical barrier to diffusion of chemotherapeutic drugs [ 109 , 110 , 111 , 112 , 113 , 114 ].…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

334

330

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Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

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Section: Tumor Microenvironmentmentioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

334

330

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“…Specifically, animal model experiments showed that mice with ECM-rich A549 tumors have significant less Cy5.5-labled glycol chitosan NPs infiltration than ECM-less SCC7 tumors [147]. Treatment with hyaluronidase (HAase), which disrupts ECM, dramatically increased the penetration of Cy5.5-labled glycol chitosan NPs in ECM-rich A549 tumors [147]. Inspired by the findings, recombinant human HAase PH20 was conjugated on the surface of poly (lactic-co-glycolic acid) (PLGA) NPs to modulate ECM.…”

Section: Nanoparticle-based Strategiesmentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

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“…Ultrasound, as a component of drug-delivery modalities, has many attractive features including simplicity and cost-effectiveness 1 - 14 . Tumor sonication can be performed non-invasively, and ultrasound wave can be directed toward deeply located tumor sites in precise energy-deposition patterns 15 - 18 .…”

Section: Introductionmentioning

confidence: 99%

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

et al. 2018

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Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery.Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets).Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy.Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release.

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Extracellular matrix remodeling in vivo for enhancing tumor-targeting efficiency of nanoparticle drug carriers using the pulsed high intensity focused ultrasound

Cited by 112 publications

References 30 publications

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Complex interplay between tumor microenvironment and cancer therapy

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

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